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Microglia are the primary immune cells in the central nervous system. The activation is of microglia crucial in neurological injury and neurodegenerative diseases. In recent years, research on microglia-targeted therapies has gained increasing attention. Microglia replacement therapy has shown promising results in treating various neurological diseases. This therapy involves the forced removal of dysfunctional microglia and their replacement with fully differentiated microglia through drug or gene targeting. This article discusses the potential pathophysiological mechanisms and effective therapeutic strategies of microglia replacement therapy in neurological diseases, including Alzheimer's disease and stroke. Moreover, it serves as a reference for the in-depth study of neurobiological mechanisms and treatment of neurological diseases. [ABSTRACT FROM AUTHOR]

AIM: To explore the impact of sphingosine 1-phosphate receptor 5 （S1PR5） on lipopolysaccharide（ LPS）-induced neuroinflammation and cognitive-behavioral impairments in mice, alongside the anti-inflammatory impacts on BV2 cells and associated mechanisms. METHODS: （1） C57BL/6 wild-type （WT） mice and homozygous S1PR5 knockout（ KO） mice were utilized and categorized into WT control, WT-LPS, S1PR5 KO control, and S1PR5 KOLPS groups using the random number method. Neuroinflammatory models in mice were induced by a single intraperitoneal injection of 5 mg/kg LPS in the WT-LPS and S1PR5 KO-LPS groups, while an equivalent volume of saline was injected into the WT control and S1PR5 KO control groups. Following 7 days of modeling, the Morris water maze test was conducted, followed by the collection of brain tissues from each group of mice. Hippocampal tissue sections were stained with Nissl. The mRNA expression levels of tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β） and IL-6 in hippocampal tissues were determined using RT-qPCR. Western blot and tissue immunofluorescence techniques were employed to assess the expression of nucleotide-binding oligomerization domain-like receptor protein 3（ NLRP3） in hippocampal tissues.（ 2） The BV2 cells underwent LPS stimulation to induce an inflammatory response and were treated with either the S1PR5 agonist A971432 or lentiviral overexpression of S1PR5. The effects of S1PR5 agonism or overexpression on S1PR5, IL-1β, IL-6, TNF-α, and CD206 were assessed using RT-qPCR. Additionally, CD206 expression was examined via cellular immunofluorescence. Western blot was employed to analyze the protein levels of microglia polarization markers CD206, inducible nitric oxide synthase （iNOS）, cyclooxygenase 2 （COX2）, and NLRP3, as well as p-NF-κB, cleaved caspase-1, and IκBα. RESULTS: （ 1） Findings from in vivo experiments indicated that S1PR5 KO notably exacerbated LPS-induced memory impairments in mice, alongside increased mRNA levels of IL-1β and IL-6, and increased protein levels of NLRP3 in the hippocampus.（ 2） The presence of S1PR5 in BV2 cells remained unaffected by variations in A971432 concentration and exposure duration.（ 3） Activation of S1PR5 or its overexpression significantly mitigated LPS-induced expression of IL-1β, IL-6, and TNF-α, while concurrently enhancing CD206 expression in BV2 cells at the mRNA level. At the protein level, it led to a noteworthy increase in CD206 expression, indicative of M2-type macrophages, and a reduction in the expression of iNOS and COX2, markers of M1-type macrophages. Furthermore, it downregulated NLRP3, p-NF-κB, and cleaved caspase-1 expression, while upregulating IκBα expression. CONCLUSION: S1PR5 deficiency exacerbates cognitive deficits in mice by promoting neuroinflammatory responses induced by LPS. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage refers to bleeding caused by non-traumatic rupturing of blood vessels within the brain, which is a serious neurological disorder. Its main pathophysiological characteristics include massive bleeding and neuron death, which impair the neuroimmune system and severely affect the patient’s prognosis. Iron ion homeostasis is crucial for maintaining normal neurological function. However, following intracerebral hemorrhage, disrupted iron metabolism leads to iron accumulation in the brain. Excessive iron participates in neuroinflammatory responses by activating inflammatory signaling pathways and regulating the function of inflammatory cells, while neuroinflammatory cells also participate in regulating the transportation and storage of iron ions. The interaction between the two exacerbates neurol damage. This article reviews the progress of research on the correlation between neuroinflammation and brain iron metabolism after intracerebral hemorrhage, aiming to provide a reference for the clinical treatment of intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Objective To analyze the molecular mechanism by which miR-384 regulates inflammation in microglia. Methods BV2 microglial cells were treated with 100 ng/mL LPS for 24 hours to establish an in vitro model of neuroinflammation. miR-384 mimics and mimic NC were transfected into BV2 cells, and RT-qPCR was used to detect the mRNA expression levels of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), hexokinase 2 (HK2), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Potential targets of miR-384 were predicted using the miRDB database, and dual-luciferase reporter assays verified the targeting relationship between miR-384 and PFKFB3. The expression levels of HK2 and PFKFB3 proteins were detected by Western blot after overexpression of miR-384. Results LPS induced the expression of inflammatory genes IL-6 and IL-1β in BV2 cells and increased lactic acid levels in the cell supernatant. Overexpression of miR-384 inhibited the LPS-induced increase in lactic acid. Additionally, miR-384 overexpression suppressed the upregulation of the glycolytic gene PFKFB3 induced by LPS, while inhibition of miR-384 further increased PFKFB3 expression. No significant effects were observed on the glycolytic gene HK2. Dual-luciferase reporter assays confirmed that PFKFB3 is a downstream target of miR-384. Furthermore, overexpression of miR-384 inhibited the expression of IL-1β and IL-6, while inhibition of miR-384 produced the opposite effects. Conclusion miR-384 directly targets the glycolytic gene PFKFB3 and regulates LPS-induced glycolysis and neuroinflammatory responses. [ABSTRACT FROM AUTHOR]

Objective: To evaluate effect of diammonium glycyrrhizinate (DG) on lipopolysaccharide (LPS)-induced TLR4/ NF- ΚB inflammatory signaling pathway in BV2 microglial cells and to explore its potential regulatory mechanisms on ameliorating neuroinflammation. Methods: BV2 microglia injury model was induced by LPS and treated with 20 and 60 μmol/L DG. MTS was used to determine vitality of cells. NO level secreted by cells was detected by Griess. Inflammatory factors TNF-α, IL-6, and IL-1β levels in cell supernatant were measured by ELISA. TNF- α, IL-6, IL-1β, TLR4 and MyD88 mRNA levels were detected by RT-qPCR. Western blot was used to determine expressions of TLR4, MyD88, NF- ΚB, p-NF- ΚB, IΚB-α and p-IΚB-α proteins of cells. Results: Compared with control group, LPS-treated BV2 microglia had significantly lower viability (P<0.05), significantly higher NO secretion (P<0.05), significantly up-regulation levels of inflammatory factors TNF- α, IL-6 and IL-1β (P<0.05), and significantly higher mRNA levels of TNF-α, IL-6, IL-1β, TLR4 and MyD88 (P<0.05), TLR4, MyD88, NF- ΚB, p-NF- ΚB, IΚB-α, and p-IΚB-α protein expressions were significantly increased (P<0.05). Compared with LPS group, BV2 microglia intervened with different concentrations of DG had significantly higher viability (P<0.05), significantly lower NO secretion (P<0.05), significantly lower TNF-α, IL-6 and IL-1β inflammatory factors levels (P<0.05), significantly lower mRNA levels of TNF-α, IL-6, IL-1β, TLR4 and MyD88 (P<0.05), and TLR4, MyD88, p-NF- ΚB and p-IΚB-α protein expressions were significantly reduced (P<0.05). Conclusion: DG can inhibit LPSinduced neuroinflammatory responses in microglia, whose underlying mechanism is suppression of TLR4/NF- ΚB signaling pathway. [ABSTRACT FROM AUTHOR]

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Objective To investigate the effects of the gut microbiota metabolite trimethylamine N-oxide (TMAO) on neuroinflammation and neurovascular unit damage in mice with cerebral infarction based on the NOD-like receptor protein 3 (NLRP3) signaling pathway. Methods Totally 120 male C57 mice were fed a high-fat diet containing 1% choline for 6 weeks and then were randomly divided into the sham operation (Sham) group, ischemia/reperfusion (I/R) group, and TMAO + I/R group, with 40 mice in each group. Mice in the Sham and I/R groups were fed the normal diet with purified water, while mice in the TMAO + I/R group received the high-fat diet with 0. 12% TMAO in drinking water. After 6 weeks, we established the middle cerebral artery occlusion (MCAO) models in the I/R and TMAO + I/R groups, and mice in the Sham group received a sham surgery. At 24 h after reperfusion in the I/R group and the TMAO + I/R group, and at the same time period in the Sham group, the degree of neurological deficit was evaluated using the Longa scoring method. The complete brain tissues were taken out. Western blotting was used to detect the expression levels of inflammatory proteins NLRP3, Cleaved-Caspase-1, Cleaved-IL-1β, and tight junction protein ZO-1. The TTC staining method was used to analyze the percentage of cerebral infarction volume, and the water content of brain tissue was measured and the cerebral blood flow was monitored. Results Compared with the Sham group, the Longa scores and the relative expression levels of NLRP3, Cleaved-Caspase-1, and Cleaved-IL-1β proteins in the brain tissues increased in the I/R group and the TMAO + I/R group, while the relative expression level of ZO-1 protein in the brain tissues decreased (all P<0. 05) ; the cerebral blood flow on both sides and the ratio of cerebral blood flow on the left to that on the right decreased in the I/R group and the TMAO + I/R group (all P<0. 05) ; the percentage of cerebral infarction volume and the water content of brain tissues increased in the I/R group and the TMAO + I/R group (all P<0. 05) . Compared with the I/R group, the Longa score and the relative expression levels of NLRP3, Cleaved-caspase-1, and Cleaved-IL-1β proteins in the brain tissues increased in the TMAO + I/R group, while the relative expression level of ZO-1 protein decreased (all P<0. 05) ; the cerebral blood flow on both sides and the ratio of cerebral blood flow on the left to that on the right decreased in the TMAO + I/R group (all P<0. 05) ; the percentage of cerebral infarction volume and the water content of the brain tissues increased in the TMAO + I/R group (all P<0. 05) . Conclusion The gut microbiota metabolite TMAO can promote neuroinflammation and neurovascular unit damage in mice with cerebral infarction by up-regulating the NLRP3 inflammasome-mediated inflammatory response, resulting in irreversible neurological damage. [ABSTRACT FROM AUTHOR]

AIM: To investigate the impact of Bruton tyrosine kinase (BTK) on Alzheimer disease (AD)-like pathology through the NIMA (never in mitosis gene A)-related kinase 7 (NEK7)-nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway. METHODS: 5xFAD and wild-type (WT) mice aged 2, 4 and 6 months were utilized to assess the expression of BTK, NEK7 and NLRP3 proteins in the hippocampus and cortex via Western blot and immunofluorescence. Co-immunofluorescence was conducted to identify the interaction between NEK7 and NLRP3 in the brains of 4-month-old mice. Three-month-old mice were divided into a control group and an ibrutinib treatment group, receiving intraperitoneal injections of ibrutinib (10 mg/kg) or solvent for 14 d, and were then subjected to behavioral assessments including learning and memory tests using the Morris water maze and Y-maze. Wild-type mice were induced with an AD model by intracerebroventricular injection of Aβ42. Morris water maze tests were performed after 14 d to evaluate learning and memory, followed by measurement of BTK protein levels in the brain via Western blot. BV2 microglial cells were treated with ibrutinib, followed by LPS or Aβ42 stimulation. Western blot analysis was conducted to measure the protein levels of NEK7, NLRP3, BTK and p-BTK (Y223), while immunofluorescence was used to assess the protein expression of ASC, caspase-1, NEK7 and NLRP3. RESULTS: The levels of BTK, NEK7 and NLRP3 in the brains of 5XFAD mice were significantly elevated compared to WT mice, with observed interaction between NEK7 and NLRP3 in the 5xFAD mouse brains. Ibrutinib treatment significantly improved learning and memory functions in mice compared to the AD group. In BV2 cells, pre-treatment with ibrutinib effectively suppressed the NLRP3 inflammasome pathway and NEK7 proteins in response to Aβ42 stimulation. CONCLUSION: BTK plays a regulatory role in AD-like pathology through the NEK7-NLRP3 pathway both in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Objective：To investigate the effect of high-intensity interval exercise (HIIT) on necroptosis and neuroinflammation in hippocampus of type 2 diabetes mellitus (T2DM) mice. Method：Male C57BL/6 mice fed with high-fat for ten weeks and then injected with streptozotocin (STZ) to establish the model of T2DM mice. Mice were divided into normal control group (CON, n=10), T2DM model group (T2DM, n=10), and T2DM exercise group (HIIT, n=10). Mice in HIIT group received treadmill training for 7 weeks. At the end of the experiment, the necroptosis of hippocampal neurons was determined by lactate dehydrogenase (LDH) content and propidium iodide (PI) staining. The NOD-like receptor protein 3（NLRP3) level was examined by immunofluorescence staining. The mRNA expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in hippocampus were evaluate by quantitative real-time polymerase chain reaction (qRT-PCR). The level of necroptosis and inflammatory cytokines related proteins in hippocampus were measured by the Western Blot. Result：Compared with the CON group, the LDH release level was significantly increased (P<0.0001), the number of PI-stained positive cells and the expression level of necroptosis related proteins were increased in T2DM group. The fluorescence intensity of NLRP3, the expression of NLRP3, caspase-1, cleaved caspase-1 protein and inflammatory cytokines iNOS, IL-6, TNF-α and IL-1β were significantly increased (P<0.05) in T2DM group. After 7 weeks of the HIIT intervention, the hippocampal LDH release level of HIIT group was significantly lower than T2DM group (P<0.0001), the number of PI-stained positive cells and the expressions level of necroptosis related proteins was also decreased. The fluorescence intensity of NLRP3 and the expression of NLRP3, caspase-1, Cleaved caspase-1 protein and the expression levels of proinflammatory factor were all decreased in HIIT group compared to the T2DM group (P<0.05). Conclusion：Necroptosis was found in the hippocampal tissue of T2DM mice. HIIT can inhibit the necroptosis and eventually reduce the inflammatory response in the hippocampal tissue of T2DM mice. [ABSTRACT FROM AUTHOR]

Objective：To explore the possible mechanism of regular aerobic exercise in improving the learning and memory function in rats with middle cerebral artery occlusion reperfusion (MCAO/R). Method：Total of 36 SD rats were randomly divided into 3 groups：sham operation group (IS group), aerobic exercise group (AE group), and model group (IC group). MCAO/R models were established in the IC and AE groups, while the IS group underwent the same arterial dissection without occlusion. After model establishment, the rats in the AE group were trained on a treadmill for 14 days, while the rats in the IS group and IC group were only placed on the treadmill for the same duration without running. The neurological function of the rats in each group was scored, the cerebral infarction focus of the rats was observed by magnetic resonance imaging T2WI scanning before and after the intervention, and the recognition and memory ability of the rats was detected by the new object recognition experiment before and after the intervention. The Western Blot was used to detect the expression of NLRP3, caspase-1, and GSDMD in the hippocampus, and immunohistochemistry was used to detect the activation of microglia in the CA1 region of the ischemic hippocampus. The levels of IL-1β and IL-18 were detected by ELISA. The expression and co-localization of IBA1 with NLRP3, caspase-1, and GSDMD were detected by immunofluorescence co-labeling assay. Result：Before intervention, the neurological function score and the signal intensity of the left cerebral cortex hippocampus of the IC Group were significantly higher than that of the IS group (P<0.05), and the resolution of new objects decreased significantly (P<0.05). There were no significant differences between the AE and IC groups in the proportion of neurological deficit, cerebral infarction volume and novel object recognition rate (P>0.05). After 14 days of treadmill training intervention, compared with IC group, the AE group showed significantly lower neurological function scores (P<0.05), reduced the percentage of cerebral infarction volume (P<0.05), improved object recognition ability (P<0.05), improved pathology in hippocampal CA1 area, reduced microglia activation level (P<0.05), decreased levels of IL-1β and IL-18 (P<0.05), and significantly reduced expression of NLRP3, caspase-1 and GSDMD proteins (P<0.05). In addition, compared with the IC group, the accumulative optical density of NLRP3, GSDMD in CA1 and caspase-1 in CA3 regions of the ischemic hippocampus in the AE group was significantly decreased, and the number of IBA1 and NLRP3, IBA1 and GSDMD double-positive cells was significantly decreased (P<0.05). Conclusion： Regular aerobic exercise can improve the ability of recognition and memory in MCAO/R rats, which may be related to the inhibition of hippocampal microglia pyroptosis and activation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the protective effects of flavonomaside on HT22 mouse hippocampal neuronal cells by inhibiting the inflammatory response induced by lipopolysaccharide (LPS) in mouse microglia (BV2) and elucidate the underlying mechanisms. Methods: BV2 cells were categorized into control (Con), LPS model (1 μg/mL), flavonomaside low, medium, and high dose groups (50, 100, 200 μmol/L respectively), TLR4 inhibitor group (TAK, 10 μmol/L), and TAK+flavonomaside group (10 μmol/L+200 μmol/L). Nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels in supernatants and cell viability were quantified. Western blot assessed the protein levels of TLR4, Myd88, NF-κB p65, and phosphorylated NF-κB p65 in BV2 cells. The BV2 cell supernatant from each group acted as conditioned medium (CM) on HT22 cells to measure cell viability and observe morphological changes. Western blot also detected the protein levels of Bax, Bcl-2, cleaved Caspase-3, and Caspase-3 in HT22 cells. Results: No significant difference in BV2 cell viability was observed with varying flavonomaside concentrations compared to the Con group. The flavonomaside (200 μmol/L) group showed a significant reduction in NO, TNF-α, and IL-6 secretion compared to the LPS group (P

Abstract: Intracerebral hemorrhage refers to bleeding caused by non-traumatic rupturing of blood vessels within the brain, which is a serious neurological disorder. Its main pathophysiological characteristics include massive bleeding and neuron death, which impair the neuroimmune system and severely affect the patient’s prognosis. Iron ion homeostasis is crucial for maintaining normal neurological function. However, following intracerebral hemorrhage, disrupted iron metabolism leads to iron accumulation in the brain. Excessive iron participates in neuroinflammatory responses by activating inflammatory signaling pathways and regulating the function of inflammatory cells, while neuroinflammatory cells also participate in regulating the transportation and storage of iron ions. The interaction between the two exacerbates neurol damage. This article reviews the progress of research on the correlation between neuroinflammation and brain iron metabolism after intracerebral hemorrhage, aiming to provide a reference for the clinical treatment of intracerebral hemorrhage.

Vascular cognitive impairment (VCI) denotes a wide range of cognitive deficiencies resulting from cerebrovascular risk factors and cerebrovascular diseases. Sirtuin 1 (SIRT1), as a deacetylase, can mediate the deacetylation of histones and non-histone proteins. It is involved in regulating multiple pathophysiological processes of VCI, including neuroinflammation reduction, oxidative stress inhibition, cell apoptosis decrease, and blood-brain barrier protection, serving as a target for VCI treatment. This paper summarizes SIRT1 and the molecular mechanisms of targeting SIRT1 in order to provide a reference for the clinical treatment of VCI.

Objective To investigate the mechanism of SUMO-specific protease 1 (Senp1) involved in neuronal pyroptosis in subarachnoid hemorrhage (SAH). Methods A total of 95 male C57BL/6 mice (6~8 weeks old) were randomly divided into sham group (n=15), SAH groups (for 6, 12, 24, 48 and 72 h, respectively, n=8, 7, 17, 6 and 6), SAH+AAV9-NC group (n=19), and SAH+AAV9-sh-Senp1 group (n=17). Mouse model of SAH was established by intravascular puncture in the left internal carotid artery. Neurobehavioral scoring was used to evaluate neurological function, HE staining and FJC staining were employed to observe brain injury, RT-PCR was conducted to detect the knockdown of Senp1, Western blotting was applied to measure the expression of Senp1, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), gasdermin D (GSDMD), PYD and CARD domain containing (ASC) and Caspase-1, and immunofluorescence assay was performed to observe the locations of Senp1 and NLRP3. Results SAH caused the elevated expression of Senp1, which reached a peak in 24 h and located in the cortical neurons. Compared with the sham group, the expression of Senp1, NLRP3, GSDMD, ASC and Caspase-1 were significantly enhanced in the SAH groups (P < 0.01), with aggravation of nerve injury and neurological deficits. Administration of AAV9-sh-Senp1 resulted in significantly improved nerve injury and function, decreased expression of above proteins (P < 0.01), and inhibited neuron pyroptosis when compared with the SAH+AAV9-NC group. Conclusion Senp1 promotes the occurrence of neuronal pyroptosis and mediates neuronal injury after SAH.

BACKGROUND: Targeted therapy based on nuclear transcription factor kappa B signaling pathway to explore neuroinflammation is increasingly worth exploring, and the advantages of Chinese medicine such as many targets, wide range, rich mechanisms, and few side effects have great potential in the treatment of various diseases. OBJECTIVE: Based on the nuclear transcription factor kappa B signaling pathway, this paper systematically expounded and summarized the research progress of kaempferol, safflower yellow, baicalin, and triptolide in the treatment of neuroinflammation after spinal cord injury. METHODS: Search terms “spinal cord injury, inflammation, anti-inflammatory, traditional Chinese medicine monomer, monomeric compound, NF-κB signaling pathway, flavonoids, glycosides, phenols, esters, alkaloids” were searched in CNKI and PubMed databases. Totally 67 articles were finally included. RESULTS AND CONCLUSION: (1) The role of nuclear transcription factor kappa B signaling pathway in the nervous system is complex and diverse, which can regulate neutrophils, microglia, astrocytes, and macrophages, and mediate the occurrence and development of inflammation after injury. (2) The effects of traditional Chinese medicine monomers such as baicalin on the degradation of nuclear transcription factor kappa B inhibitory protein, the inhibition of phosphorylation process by safflowerin on nuclear transcription factor kappa B signaling pathway, and the inhibition of kaempferol on nuclear transcription factor kappa B signaling pathway p65 nuclear translocation can reduce the impact of inflammatory response on the body, thereby promoting the recovery of neurological function. (3) The nuclear transcription factor kappa B signaling pathway can promote inflammation and immune cell migration and activation in the early stage of injury, and can promote the repair of injury site and the occurrence of fibrosis in the middle and late stages of injury. Appropriate activation of the nuclear transcription factor kappa B signaling pathway can promote the release of inflammatory factors, improve the antioxidant capacity of cells, and promote the activation of immune cells, but the over-activated nuclear transcription factor kappa B signaling pathway can easily lead to the occurrence and continuation of chronic inflammation and the inhibition of apoptosis. (4) Future research can further explore how to accurately regulate the activation level of nuclear transcription factor kappa B signaling pathway, how to achieve precise intervention for nervous system inflammation and injury, and can also focus on the preparation of traditional Chinese medicine monomers and the mechanism of action of traditional Chinese medicine monomers on signaling pathways, in order to provide more effective treatment strategies for the rehabilitation and functional recovery of neurological diseases. [ABSTRACT FROM AUTHOR]

卒中后中枢性疼痛（central post-stroke pain，CPSP）是常见的卒中并发的神经病理性疼痛综合征，严重影响卒中患者的后期康复和生活质量。近年来，CPSP的病理机制研究逐渐受到重视，而小胶质细胞作为颅内常驻的巨噬细胞，被认为在CPSP发生发展中起重要调节作用。本篇综述从生物活性因子、细胞受体和信号通路等角度总结了近年来小胶质细胞调节CPSP的研究进展，描述了多个化合物对CPSP的临床前治疗作用，以期促进CPSP靶向治疗策略的发展。 Abstract: Central post-stroke pain (CPSP) is a common neuropathic pain syndrome associated with stroke, which severely affects the outcome and life quality of stroke patients. In recent years, more and more attention has been paid to the study of the pathological mechanism of CPSP. Microglia, the resident macrophage within the central nervous system, is considered to play a critical role in the development of CPSP. The present review summarized recent research progress of microglia in mediating CPSP from the perspective of bioactive factors, cellular receptors, and signaling pathways, and described the preclinical therapeutic effects of several compounds on CPSP, hoping to promote the development of targeted therapeutic strategies for CPSP.

To optimize the processing technology of Gastrodia elata by water in which millet had been cooked and investigate the effects of LPS-induced microglia (BV2) inflammatory responses. Determination of gastrodin, p-hydroxybenzyl alcohol, parishin A, parishin B, parishin C, parishin E in the extract of Gastrodia elata by high-performance liquid chromatography (HPLC), and the content of six components were used as evaluation index, the volume ratio of water in which millet had been cooked to water, cooking time and drying temperature were selected as single factor variables. The designation of orthogonal test was based on single factor on three indicators, then optimization of the preparation technology. Comparison of the content of six components in different processed product. The neuroinflammatory cell model was induced by LPS and the cell viability was evaluated after treatment with the extract of processed products by a Cell Counting kit 8 (CCK-8) assay. The levels of TNF-α, IL-6, IL-1β in the cell culture medium were measured with ELISA kits. The protein expressions of TLR4, MYD88, P65, INOS, COX-2, IL-1β in LPS-induced BV2 cells were detected by Western blot. The results showed that the cooking time and the volume ratio of water in which millet had been cooked to water had a significant effect on the test results. The water in which millet had been cooked of Gastrodia elata processing technology: The ratio of the volume water in which millet had been cooked to water was 1:3, the boiling time was 25 min and the temperature of drying was 75 ℃. The comprehensive score of the six components in processing with water in which millet had been cooked products was higher than that of steamed products. The extract of Gastrodia elata had exhibited varying degrees of protective activity on LPS-induced BV2 cells. The results showed that the secretion of TNF-α, IL-6, IL-1β was significantly increased in BV2 microglial cells induced by LPS compared with the normal control group (P

Post-stroke cognitive impairment, characterized by cognitive dysfunction, is a common complication of stroke and has a direct impact on the quality of life of ischemic stroke patients. Previous studies have found that astrocytes play an important role in the pathogenesis of PSCI. In addition, extracellular vesicles (EVs) have been recognized as an important medium for intercellular communication and are involved in various pathophysiological processes by carrying and transporting various cargoes. Astrocyte-derived extracellular vesicles (ADEVs) may communicate with other brain cells to improve PSCI by enhancing synaptic plasticity, modulating neuroinflammation, regulating angiogenesis and autophagy. This review clarifies the multiple effects of ADEVs on the development of PSCI, offers new strategies for studying the underlying mechanisms of PSCI, and further explores the potential uses of ADEVs as novel drugs and biomarkers in the diagnosis and treatment of PSCI.

Neurodevelopmental disorders (NDDs) are chronic developmental brain disorders that can affect cognition, motor, social adaptation, behavior and so on due to multiple genetic or acquired causes. Natural polysaccharides are synthesized by living organisms, located in the cell wall, inside and between cells, and outside the cells, and are essential components of life activities. Previous studies have found that natural polysaccharides play an important role in neurological diseases, which mainly ameliorate the behavioral abnormalities and clinical symptoms caused by anti-oxidative stress, anti-neuronal apoptosis, anti-neuroinflammation, anti-excitatory amino acid toxicity, and regulation of the brain-gut axis. This review summarizes the intervention role of 17 bioactive polysaccharides from plants and fungi in neurological diseases, aiming to provide new ideas for the research and treatment of NDDs.

Stroke is the disease with high morbidity, disability and mortality worldwide. The bloodbrain barrier (BBB) is an important functional structure that maintains the stability of the microenvironment in the brain and is disrupted in the early stages of stroke, which is a major complication of stroke and exacerbates the damage to brain tissue caused by stroke. At the same time, the degree of structural and functional integrity of the BBB is a key predictor of the risk of hemorrhagic transformation after thrombolytic therapy and thrombectomy after stroke, and an important therapeutic target for preventing further brain damage in acute stroke. This article reviews the relevant studies on BBB structure, function, ischemic injury changes, and potential therapeutic targets in recent years to provide ideas for further knowledge and understanding of ischemic stroke BBB changes and protective drug development. This article reviews the relevant studies on BBB structure, function, ischemic injury changes and potential therapeutic targets in recent years to provide ideas for further knowledge and understanding of BBB changes in ischemic stroke and protective drugs development. [ABSTRACT FROM AUTHOR]

To optimize the processing technology of Gastrodia elata by water in which millet had been cooked and investigate the effects of LPS-induced microglia (BV2) inflammatory responses. Determination of gastrodin, p-hydroxybenzyl alcohol, parishin A, parishin B, parishin C, parishin E in the extract of Gastrodia elata by high-performance liquid chromatography (HPLC), and the content of six components were used as evaluation index, the volume ratio of water in which millet had been cooked to water, cooking time and drying temperature were selected as single factor variables. The designation of orthogonal test was based on single factor on three indicators, then optimization of the preparation technology. Comparison of the content of six components in different processed product. The neuroinflammatory cell model was induced by LPS and the cell viability was evaluated after treatment with the extract of processed products by a Cell Counting kit 8 (CCK-8) assay. The levels of TNF-α, IL-6, IL-1β in the cell culture medium were measured with ELISA kits. The protein expressions of TLR4, MYD88, P65, INOS, COX-2, IL-1β in LPS-induced BV2 cells were detected by Western blot. The results showed that the cooking time and the volume ratio of water in which millet had been cooked to water had a significant effect on the test results. The water in which millet had been cooked of Gastrodia elata processing technology: The ratio of the volume water in which millet had been cooked to water was 1:3, the boiling time was 25 min and the temperature of drying was 75 °C. The comprehensive score of the six components in processing with water in which millet had been cooked products was higher than that of steamed products. The extract of Gastrodia elata had exhibited varying degrees of protective activity on LPS-induced BV2 cells. The results showed that the secretion of TNF-α, IL-6, IL-1β was significantly increased in BV2 microglial cells induced by LPS compared with the normal control group (P<0.001). Compared with the LPS group, the two extract of Gastrodia elata significantly decreased the expression level of TNF-α (P<0.05), IL-6 (P<0.05, P<0.001), IL-1β (P<0.05, P<0.001) in LPS-induced BV2 microglial cells. The result of Western blot showed that PZH significantly inhibited the LPS-induced TLR4/MYD88/NF-κ B signaling pathway activation, and decreased the protein expressions of TLR4 (P<0.01), MYD88 (P<0.01, P<0.05), P65 (P<0.01), INOS (P<0.05), COX-2 (P<0.05, P<0.001), IL-1β (P<0.001). The optimized processing technique is simple, stable and feasible. The mechanism of processed drugs of Gastrodia elata may reduce inflammatory factor expression by inhibiting the TLR4/MYD88/NF-κ signaling pathway. [ABSTRACT FROM AUTHOR]

As a kind of gas signaling molecules, nitric oxide (NO) is involved in the regulation of diverse physiological functions. In the central nervous system, physiological concentrations of NO participate in maintaining physiological neuropsychiatric functions, whereas high concentrations of NO are neurotoxic, which promote several neuropsychiatric diseases through a wide variety of pathological processes. This review discusses the metabolism and functions of NO in the central nervous system. Taking Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, depression and autism spectrum disorder as examples, the relationship and pathogenic mechanism of NO with neurodegenerative diseases, neuroinflammatory diseases, mental disorders and neurodevelopmental disorders are described, which provides ideas and impetus for further development of pathogenic mechanism and therapeutic drugs. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Stroke is the property of Chinese Journal of Stroke Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: Long non-coding RNAs (lncRNAs), as important regulators of the inflammatory response, are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE: To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways, pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS: PubMed was searched using the search terms of “ischemic stroke, long non-coding RNA, neuroinflammation, immune function, signal pathway, microglia, astrocytes, oligodendrocyte, mechanism,” and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION: In the early stage of ischemic stroke, the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain, promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses. As an important pathogenesis factor in ischemic stroke, the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke, and it needs to be suppressed promptly in the early stage. Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia, astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects. LncRNAs, as important regulatory factors of the inflammatory response, inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB, lncRNA-miRNA-mRNA axis, Rho-ROCK, MAPK, AKT, ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke. Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model, but no clinical trials have been conducted. Therefore, it remains to be further explored about whether lncRNAs can be safely applied in clinical practice. At present, there are many therapeutic drugs for the treatment of ischemic stroke, but there are relatively few studies on the application of lncRNAs, exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology, which need to be further explored. lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity. In future studies, more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored, in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke. [ABSTRACT FROM AUTHOR]

Vascular dementia is a cognitive impairment caused by cerebrovascular disease. Its pathogenesis is derived from a series of pathological processes such as low cerebral blood perfusion caused by cerebrovascular damage. Microglia is an important part of the human innate immune system. Under the stimulation of different microenvironmental signals, microglia can differentiate into M1 type with pro-inflammatory effects and M2 type with anti-inflammatory effects, and produce a variety of cytokines with neurotoxic or neuroprotective effects. In recent years, regulating the polarization of microglia and reducing excessive inflammatory response have become important strategies for the treatment of neurodegenerative diseases. By introducing the main signaling pathways related to microglia polarization and the role of microglia polarization-mediated neuroinflammation in vascular dementia, this paper clarified the important role of microglia polarization balance in the treatment of vascular dementia and provided new ideas for related clinical research. [ABSTRACT FROM AUTHOR]

It has been found that overactivation of Poly(ADP-ribose) Polymerase-1 (PARP-1) after radiotherapy is closely related to the neuroinflammatory response, which is the main pathogenesis of radiation- induced cognitive decline (RICD). This article analyzed the pathogenic mechanisms of neuroinflammatory responses in RICD, including Microglia activation, astrocyte proliferation, oligodendrocyte destruction, hippocampal microenvironmental alterations, and blood-brain barrier damage, and reviewed the research progress on the exacerbation of RICD by PARP-1 mediating neuroinflammatory response through these common mechanisms. Finally, the potential protective effects of PARP-1 inhibitors against RICD are discussed, aiming to provide a new direction for the development RICD prevention and treatment drugs. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Suhexiang Pill on regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway on neuroinflammation and neuronal apoptosis in rats with acute cerebral infarction. Methods: SD rats were divided into model group, sham surgery group, low-dose Suhexiang pill group (2.5 mL/kg), medium dose Suhexiang pill group (5 mL/kg), high-dose Suhexiang pill group (10 mL/kg), nimodipine group (2 mg/kg), SQ22536 (cAMP inhibitor) group (2.13 mg/kg), and high-dose Suhexiang pill+SQ22536 group (10 mL/kg+2.13 mg/kg), with 24 rats in each group. Except for the sham operated group where only the arteries were isolated, all other groups of rats were required to construct acute cerebral infarction models. After successful modeling, medication treatment was performed once a day for 2 weeks. Zea Longa scoring method was used to detect neural function; Dry wet weight method was used to detect the water content of rat brain tissue; Measure the volume of cerebral infarction with 2,3,5-triph-enyltetrazole chloride (TTC) staining; Enzyme-linked immunosorbent assay (ELISA) was used to detect tumor necrosis factor-a (TNF-α), Interleukin(IL)-6, IL-1B, CAMP level in rat brain tissue; Hematoxylin eosin (HE) staining was used to detect pathological changes in rat neurons; TUNEL staining was used to detect neuronal apoptosis; Western blot was used to detect the expression of cleaved aspartate specific cysteine protease-3 (Cleaved Caspase-3), Bcl-2 related X protein (Bax), and p-PKA protein in rat brain tissue. Results: Compared with the sham surgery group, neurological function score, neuronal apoptosis rate, TNF-a, IL-1 β, IL-6 levels, cerebral infarction volume, Bax, Cleaved Caspase-3 protein expression, and brain tissue water content increased in model group, the expression of cAMP and p-PKA proteins was reduced (P<0.05), and the pathological damage to the CAl region of the hippocampus in brain tissue was severe. Compared with the model group, the low-dose Suhexiang pill group, medium dose Suhexiang pill group, high-dose Suhexiang pill group, nimodipine group of rat neurological function score, TNF-α, IL-1β, IL-6 level, brain tissue water content, neuronal apoptosis rate, cerebral infarction volume, Bax, Cleaved Caspase-3 protein expression decreased, CAMP and p-PKA protein expression increased (P<0.05), alleviation of pathological damage in hippocampal CA1 region of brain tissue, the trend of changes in corresponding indicators in the SQ22536 group was opposite to the above (P<0.05); SQ22536 weakened the inhibitory effect of high-dose Suhexiang Pill on neuroinflammation and neuronal apoptosis in rats with acute cerebral infarction. Conclusion: Suhexiang Pill may inhibit neuroinflammation and neuronal apoptosis in rats with acute cerebral infarction by activating the cAMP/PKA pathway. [ABSTRACT FROM AUTHOR]

The loss of dopaminergic neurons in the substantia nigra compacta and the aggregation of α- synuclein are the hallmark symptoms of Parkinson's disease (PD), a prevalent neurodegenerative condition. The pathological mechanisms of PD are very complex, and microglia activation-mediated neuroinflammation has recently been found to be an important factor in dopaminergic neuronal loss in PD. Current pharmacological treatments can only alleviate the symptoms of dyskinesia but cannot slow down the pathological process. Exercise, as a non-pharmacological physical intervention, has been shown to be helpful in preventing and delaying the onset of neurodegenerative pathologies, and moderate exercise produces some anti-inflammatory effects and reduces dopaminergic neuron loss. However, the regulatory mechanisms of exercise in ameliorating microglia-mediated neuroinflammation and preventing the pathological process of PD are not well understood. Some studies have found that exercise can ameliorate factors associated with PD, such as abnormally aggregated α-synuclein, brain-derived neurotrophic factor levels, autophagy, and oxidative stress. Therefore, this paper describes the molecular mechanism of exercise to improve microglia-mediated neuroinflammation in the prevention of Parkinson's disease from the above aspects and provides new therapeutic targets for the prevention and treatment of PD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a common neurodegenerative disease, which is mainly caused by brain lesions. The activation of complement system plays an important role in the process of AD lesions. The activated complement can bind to cell membrane receptors and regulate downstream signals. Therefore, inhibiting complement activation provides a new idea for AD treatment. This article reviews the progress in the mechanism and drug development of complement activation in AD, which may provide a new perspective for the diagnosis, treatment and drug development of AD. [ABSTRACT FROM AUTHOR]

To explore the role and mechanism of NF-κB / HIF-1α signaling pathway in the neuroinflammation caused by chronic cerebral hypoperfusion. The chronic cerebral hypoperfusion mouse model was established by unilateral common carotid artery ligation (Unilateral Common Carotid Artery Occlusion UCCAO), randomly divided into 3 large groups of 50 mice, normal control group, sham group and UCCAO group. Each large group was divided into 5 groups according to 1 d, 3 d, 7 d, 14 d and 21 d. Learning and memory abilities were assessed using the Morris water maze. The relative expression levels of HIF-1α mRNA and NF-κB p65 mRNA in mouse brain tissues were determined by RT-PCR. TNF-α and IL-1β were detected by ElISA. Compared with the sham group, learning and memory was significantly decreased in the UCCAO group (P<0.01). Compared with the sham group, the relative expression levels of HIF-1α mRNA and NF-KBp65 mRNA in UCCAO mice increased significantly (P<0.01), while the relative expression levels of HIF-1α mRNA and NF-κB p65 mRNA increased significantly from 3 d and peaked at 7 d, and the relative expression level still increased significantly after 21d (P<0.01). Compared with the sham group, TNF-α and IL-1β were significantly increased in the UCCAO group (P<0.01). 1. Chronic persistent cerebral hypoperfusion can lead to progressive cognitive dysfunction in mice. 2. Ischia and hypoxia after CCH can not only activate HIF-1α signaling pathway, but also be a stimulating factor of NF-κB signal transduction pathway. These two signaling pathways have many intersections, and NF-κB activation provides positive feedback on the regulation of HIF-1α and the formation of inflammatory response. [ABSTRACT FROM AUTHOR]

Objective To construct a model of Fat-1/APPPS1 transgenic mice and a cellular model of microglia and explore the improvement effect and underlying mechanism of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the learning and memory abilities of APPPS1 mice by regulating microglial activation and polarization. Methods After the male mice with heterozygous Fat-1 genotype were mated with the female ones with heterozygous APPPS1 genotype, genetic identification was used to screen the male offspring with Fat-1/APPPS1 genotype. Then after the male wild-type (WT) mice and those with Fat-1, Fat-1/APPPS1, and APPPS1 genotypes were bred until 9 months old, their learning and memory abilities were evaluated with Morris water maze (MWM) test. In addition, gas chromatography-mass spectrometry (GC-MS) was performed to detect the concentration of PUFAs in the brain, and immunohistochemistry (IHC) was applied to detect the deposition of β-amyloid protein (Aβ) in the hippocampal regions. Moreover, immunofluorescence assay, qRT-PCR, and enzyme-linked immunosorbent assays (ELISA) were conducted to measure inflammation, and transcription and expression of Iba-1 (indicating the microglial activation) and CD86 and CD206 (indicating microglial polarization) in central nervous system (CNS). After pretreated with DHA+EPA (25 μmol/mL ∶25 μmol/mL), microglial model of inflammatory injury was established in immortalized mouse BV2 cells induced by LPS (1 μg/mL). Afterwards, immunofluorescence assay, qRT-PCR and Western blotting were used to detect inflammation and microglial activation and polarization. Results Compared with the APPPS1 mice, endogenous n-3 PUFAs effectively improved the learning and memory disorders in Fat-1/APPPS1 ones (P < 0.05), remarkably alleviated Aβ deposition in the hippocampal regions (P < 0.05), evidently reduced CNS inflammation and microglial activation (P < 0.05) and transformed the activated microglia from M1 to M2 (P < 0.05). Furthermore, BV2 cells with DHA+EPA pretreatment obviously resisted LPS-induced cellular inflammation and induced activated ones from M1 to M2 (P < 0.05). Conclusion n-3 PUFAs inhibit the microglial activation, regulate the microglial polarization from M1 to M2, reduce CNS inflammation, and thus alleviate learning and memory disorders in APPPS1 mice.

Objective To investigate the neuroprotective effects and mechanisms of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Parkinson's Disease (PD) animal models. Methods SD rats were divided into five groups: sham-operated group (Sham group), PD group (Parkinson's modeling group), PD + PACAP_low concentration group (modeling + 5 μg / kg of PACAP intranasal administration according to body weight), PD+ PACAP_medium concentration group (modeling + 10 μg / kg of PACAP intranasal administration according to body weight), PD+ PACAP_high concentration group (modeling + 20 μg / kg of PACAP intranasal administration according to body weight). Each group included 10 animals. The four PD models were established by injecting lipopolysaccharide solution into the substantia nigra of SD rats. The Sham group was operated in the same way but injected with saline. The behavioral performance of the rats was assessed using the rotarod test. The concentration of glutamate (Glu) and the levels of α-synuclein (α-syn) in the substantia nigra were detected using ELISA. The expression levels of α-syn in the substantia nigra, as well as those of κ-light chain of nuclear factoractivated B-cells (NF- κB) and inhibitor of nuclear factor κB (IκBα) were detected using WB analysis. Quantitative Polymerase Chain Reaction (qPCR) was used to detect the mRNA expression levels of the rat nigral inflammatory factors Tumor Necrosis Factor α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6). WB and immunofluorescence methods were used to detect the levels of nuclear transcription factor Glial Fibrillary Acidic Protein (GFAP) to observe the activation level of astrocytes, and the TUNEL method was used to detect apoptosis in nigrostriatal neurons. Results (1) Behavioral results from the rotarod test indicated that compared to the Sham group, the PD group had a shorter latency and an increased number of falls (37.20±5.27 falls /min). In comparison to the PD group, the PACAP group showed a prolonged latency and a decreased number of falls (14.50±2.32 falls/min). As the concentration of PACAP increased, the latency in the PACAP group was prolonged, and the number of falls decreased (P

Objective To investigate the role of transient receptor potential melatonin 2 （TRPM2） ion channels in microglia and astrocytes in temporal lobe epilepsy （TLE） -associated neuroinflammation. Methods Rats were randomly divided into the control group and epilepsy group. Seizure models were induced by lithium chloride-pilocarpine in the epilepsy group， and those in the control group were injected with the same dose of saline. The TLE rats were randomly divided into 7 subgroups according to the observation time after model establishment： acute phase （3 h group， 6 h group， 1 d group， 2 d group）， latent phase （14 d group） and chronic phase （30 d group， 90 d group） subgroups （n = 5）. The expression level of TRPM2 in the hippocampus of TLE rats at different stages were detected， and the cellular localization of TRPM2 in the brain of TLE rats was investigated. BV2 and C8 cell lines were induced by hydrogen peroxide （H2O2）. The levels of IL1-β， IL-6 and TNF-α released by BV2 and C8 cells were observed by ELISA. The levels of TRPM2， poly （ADP-ribose） polymerase 1 （PARP-1）， glycogen synthase kinase-3β （GSK-3β） and phosphorylated nuclear factor-κb p65 （p-NF-κb p65） were measured in H2O2-induced BV2 and C8 cells. Meantime， the activity of Calcineurin （CaN） in H2O2-induced BV2 was observed. Results The TRPM2 expression in 2d epileptic rat hippocampus was increased （P < 0.05）. The expression of TRPM2 and the release of inflammatory cytokines were increased in H2O2 induced-BV2 and C8 cells （both P < 0.05）. H2O2 could up-regulate the expression of PARP-1 and p-NF-κB p65 and enhance the activity of CaN in BV2 cells （all P < 0.05）. Conclusions Oxidative stress can up-regulate the expression levels of TRPM2 and pro-inflammatory cytokines in microglia and astrocytes. Oxidative stress caused by recurrent epilepsy may mediate the occurrence of TLE-associated neuroinflammation through the TRPM2/ CaN/p-NF-κB p65 pathway in microglia.

BACKGROUND: Patients with Alzheimer’s disease mainly show cognitive and memory dysfunctions. Aerobic exercise can inhibit endoplasmic reticulum stress and improve cognitive function of the patients. However, whether aerobic exercise can inhibit endoplasmic reticulum stress dependent neuroinflammation is still unclear. OBJECTIVE: To explore the effect of aerobic exercise on neuroinflammation and cognitive impairment in a mouse model of Alzheimer’s disease. METHODS: Fifty C57BL/6J wild-type male mouse mice were randomly divided into wild-type control and wild-type exercise groups, while another 50 APP/ PS1 double transgenic male mice were randomly divided into Alzheimer’s disease group and Alzheimer's disease exercise group, with 25 mice in each group. Mice in the wild-type exercise and Alzheimer's disease exercise groups received aerobic exercise training (treadmill training, 45 min/d, 12 m/min, 5 d/wk, 8 weeks in total). Mice in the wild-type control and Alzheimer’s disease groups were placed on the quiet running platform. Morris water maze test was used to detect the cognitive ability of mice. Hematoxylin-eosin staining and Nissl staining were used to detect hippocampal tissue damage in mice. Thioflavin-S staining was used to detect β-amyloid content in hippocampal tissue. Immunohistochemistry was used to detect β-amyloid and p-Tau levels in hippocampal tissue. Immunofluorescence staining was used to detect the number of positive cells for neuroinflammation-related factors in hippocampal tissue. Western blot was used to detect p-IRE1, IRE1, p-PERK, PERK, ATF6, GRP78, Bip, Caspase-12, Iba-1, and GFAP protein levels. RESULTS AND CONCLUSION: Compared with the wild-type control group, escape latency was increased, the number of times they reached the previous platform and the time they stayed on the platform were decreased, β-amyloid and Tau levels, p-IRE1/IRE1, p-PERK/PERK, ATF6, GRP78, Bip, Caspase-12, Iba-1, and GFAP protein levels, Iba-1+, Iba-1+ TNF-α+, Iba-1+ IL-6+, Iba-1+ IL-1β+, GFAP+, GFAP+ TNF-α+, GFAP+ IL-6+, GFAP+ IL-1β+ positive cells in hippocampal tissue were increased, and Iba-1+ IL-4+, Iba-1+ IL-10+, GFAP+ IL-4+, GFAP+ IL-10+ positive cells were decreased in the Alzheimer’s disease group (P < 0.05). Compared with Alzheimer’s disease group, escape latency was decreased, the number of times they reached the previous platform and the time they stayed on the platform were increased, β-amyloid and Tau levels, p-IRE1/IRE1, p-PERK/PERK, ATF6, GRP78, Bip, Caspase-12, Iba-1, GFAP protein levels, Iba-1+, Iba-1+ TNF-α+, Iba-1+ IL-6+, Iba-1+ IL-1β+, GFAP+, GFAP+ TNF-α+, GFAP+ IL-6+, and GFAP+ IL-1β+ positive cells in hippocampal tissue were decreased, and Iba-1+ IL-4+, Iba-1+ IL-10+, GFAP+ IL-4+, GFAP+ IL-10+ positive cells were increased in the Alzheimer’s disease exercise group (P < 0.05). To conclude, aerobic exercise can reduce cognitive impairment in Alzheimer’s disease mice by inhibiting endoplasmic reticulum stress and neuroinflammation in hippocampal tissue. [ABSTRACT FROM AUTHOR]

Objective: To investigate the neuroprotective mechanism of berberine on chronic hypoperfusion brain injury in mice.Methods: Unilateral common carotid artery occlusion (UCCAO) was used to establish chronic cerebral hypoperfusion model in mice.The mice were randomly divided into 6 groups (n=10) : sham operation group, model group, According to the different doses of berberine, they were divided into low-dose group, medium-dose group and high-dose group, intragastric administration for 21 days. The fine motor ability and learning memory ability of mice were evaluated by horizontal crossbar test and Morris water maze. IL-1β, NLRP3 and TNF-α were detected by ELISA. Results: Compared with the model group, the fine motor ability of middle dose and high dose berberine groups was significantly improved (P＜0.01), while low dose berberine had no significant change (P＜0.05) . Compared with model group, cognitive ability of middle dose and high dose berberine groups was significantly improved (P＜0.01), while low dose berberine had no significant change (P＜0.05) . Compared with the model group, the expression of TNF-α, IL-1β, NLRP3 in hippocampus and cortex of mice in middle and high dose berberine groups decreased significantly, significantly, while low dose berberine IL-1β of berberine had no significant change (P＜0.05) . Conclusion: Berberine can improve the fine motor ability and cognitive dysfunction of mice with chronic hypoperfusion brain injury, and reduce neuroinflammatory reaction, which has neuroprotective effect. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Food Safety & Quality is the property of Journal of Food Safety & Quality Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

AIM： To investigate the molecular mechanism of long noncoding RNA (lncRNA) SNHG1 in regulating ferroptosis to alleviate inflammation in CHME-5 human microglia induced by HIV-1 gp120 V3 loop. METHODS： CHME-5 human microglia were cultured in vitro, and were divided into 7 groups： blank group, random peptide group，gp120 V3 loop group (HIV-1 gp120 group), HIV-1 gp120+shCon group, HIV-1 gp120+SNHG1 sh2 group, HIV-1 gp120+SNHG1 sh2+ferrostatin-1(Fer-1； ferroptosis inhibitor) group, and HIV-1 gp120+SNHG1 sh2+EX527(Sirt1 inhibitor) group. Normal CHME-5 cells were treated with random peptide or gp120 V3 loop for 24 h. After pretreatment of SNHG1 sh2 cells with inhibitors for 2 h, the cells were then treated with gp120 V3 loop for 24 h. The levels of inflammatory cytokines in the cell supernatants were detected by ELISA. Western blot was used to detect the protein expression levels of solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), Sirt1 and p53. Microplate reader was used to detect the levels of intracellular ferrous ion (Fe2+ ) and malondialdehyde (MDA). RESULTS：(1) The results of ELISA showed that the expression levels of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and IL-1β in HIV-1 gp120 group were significantly higher than those in blank group (P<0. 05). Compared with HIV-1 gp120 group, the expression levels of inflammatory cytokines in HIV-1 gp120+SNHG1 sh2 group were significantly decreased (P<0. 05). Compared with HIV-1 gp120+SNHG1 sh2 group, the expression levels of inflammatory factors in HIV-1 gp120+SNHG1 sh2+Fer-1 were significantly decreased (P<0. 05), but those in HIV-1 gp120+SNHG1 sh2+EX527 group were significantly increased (P<0. 01). (2) The results of Western blot showed that compared with blank group, the expression levels of ferroptosis-related proteins SLC7A11 and GPX4 in HIV-1 gp120 group were significantly down-regulated (P<0. 01). Compared with HIV-1 gp120 group, the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2 group were significantly up-regulated (P<0. 01). Compared with HIV-1 gp120+SNHG1 sh2 group, the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly up-regulated (P<0. 05), but the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+EX527 group were significantly down-regulated (P<0. 01), and the expression level of p53 was significantly up-regulated (P<0. 05). (3) Compared with blank group, the levels of Fe2+ and MDA in HIV-1 gp120 group were significantly increased (P<0. 05). Compared with HIV-1 gp120 group, the levels of Fe2+ and MDA in HIV-1 gp120+SNHG1 sh2 group were significantly decreased (P<0. 01). Compared with HIV-1 gp120+SNHG1 sh2 group, Fe2+ and MDA in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly decreased (P<0. 05), but those in HIV-1 gp120+SNHG1 sh2+EX527 group was significantly increased (P<0. 05). CONCLUSION： Knockdown of SNHG1 can attenuate the inflammation in microglia induced by HIV-1 gp120 V3 loop, which may be achieved by regulating ferroptosis-related signaling molecules through the Sirt1/p53 signaling pathway. [ABSTRACT FROM AUTHOR]

AIM: To evaluate the effect of astaxanthin (AST) on cognitive function of intestinal ischemia/reperfusion (I/R) injury in rats and the role of autophagy. METHODS: Eight-week-old SPF-grade male Sprague-Dawley (SD) rats were randomly divided into sham group, I/R group, AST group and AST+3-methyladenine (3-MA) group, with 12 animals in each group. The superior mesenteric artery (SMA) of the rats in sham group was only exposed without clamping. The SMA in other 3 groups was clamped for 90 min, and then the arterial clamp was released to restore blood supply and perform reperfusion, thus establishing the intestinal I/R model. The rats in AST group were intraperitoneally injected with AST (45 mg·kg−1 ·d−1 )3 d before modeling, and those in AST+3-MA group were intraperitoneally injected with AST (45 mg·kg−1 ·d−1 )+3-MA (1. 5 mg·kg−1 ·d−1 )3 d before modeling. Morris water maze was used to evaluate the cognitive function of rats 48 h after surgery. Hematoxylin-eosin (HE) staining was used to evaluate intestinal tissue damage. Nissl staining of the frontal cortex was used to evaluate neuronal damage. The levels of interleukin-6(IL-6), IL-1β and tumor necrosis factor-α(TNF-α) in the frontal cortex and hippocampus were measured by ELISA kits. The protein levels of beclin-1, microtubule-associated protein 1 light chain 3(LC3) and P62 in the frontal cortex and hippocampus were detected by Western blot. RESULTS: Compared with sham group, the swimming distance of rats in I/R group was increased, with prolonged latency, elevated Chiu's score and decreased number of neurons (P<0. 01), while the levels of IL-6, IL-1β and TNF-α in the frontal cortex and hippocampus were increased (P<0. 01). Beclin-1 expression and LC3-II/LC3-I ratio in the frontal cortex and hippocampus were increased (P<0. 05 or P<0. 01). Compared with I/R group, the swimming distance and latency of rats in AST group were shortened, with decreased Chiu's score, increased neuronal number (P<0. 01), decreased IL-6, IL-1β and TNF-α levels in the frontal cortex and hippocampus (P<0. 01), and increased beclin-1 expression and decreased of P62 expression in the frontal cortex and hippocampus (P<0. 05 or P<0. 01). Compared with AST group, the swimming distance of rats in AST+3-MA group was increased, with prolonged latency, elevated Chiu's score, decreased number of neurons (P<0. 05), increased levels of IL-6, IL-1β and TNF-α in the frontal cortex and hippocampus, and decreased beclin-1 expression and LC3-II/LC3-I ratio and increased P62 expression in the frontal cortex and hippocampus (P<0. 01). CONCLUSION: Astaxanthin alleviates intestinal I/R-induced cognitive impairment in rats by promoting autophagy and inhibiting neuroinflammation. [ABSTRACT FROM AUTHOR]

Sepsis associated encephalopathy (SAE) is a common complication in patients with sepsis. It is characterized by brain dysfunction, and a considerable proportion of patients have long-term cognitive impairment. The central nervous system is one of earliest regions affected by peripheral inflammation caused by sepsis. As resident immune cells of central nervous system, microglia can coordinate inflammatory responses in brain and play an important role in the innate and adaptive immune responses of brain. Therefore, it plays a crucial role in the occurrence and development of SAE. In this paper, the functional phenotypes of microglia and their role in SAE are reviewed to explore the potential value of microglia in the prevention and treatment of SAE. [ABSTRACT FROM AUTHOR]

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To observe the improvement effect of intragastric administration of ursolic acid (UA) on cog⁃ nitive function in rats during the process of Alzheimer's disease (AD) induced by aluminium trichloride (AlCl3) and to ex⁃ plore its mechanism. Methods Twentyfour male Wistar rats were randomly divided into the blank group (n=6), UA group (n=6), AlCl3 group (n=6) and AlCl3+UA group (n=6), respectively. The rats in the blank group were given normal saline, the rats in the UA group were intragastrically administered AlCl3 to establish the AD models, and the rats in the Al⁃ Cl3+UA group were intragastrically given UA during the process of AD induced by AlCl3. After stopping intragastric admin⁃ istration for 5 d, the cognitive function of rats in each group was observed by Morris water maze test. The rats in each group were killed by decapitation after anesthesia, and the cerebral cortex and hippocampus were taken. The aluminum content in the cerebral cortex and hippocampus was determined by spectrophotometry, and the activity of acetylcholinase (AChE) in the cerebral cortex and hippocampus was detected by colorimetry. The activity of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) in cerebral cortex and hippocampus was measured, and the activity of thiobarbituric acid re⁃ actants (TBARS) was calculated. The relative expression levels of inflammatory factors TNFα, IL6, NFκB and COX2 mRNA in cerebral cortex and hippocampus were detected by realtime fluorescence quantitative PCR. Results Com⁃ pared with the blank group and the UA group, the escape latency was longer and the stay time in the original platform quad⁃ rant was shorter in the AlCl3 group (both P<0. 05) . Compared with the AlCl3 group, the escape latency was shorter and the stay time in the original platform quadrant was longer in the AlCl3+UA group (both P<0. 05) . The content of aluminum in cerebral cortex and hippocampus in the AlCl3 group was higher than that in the other groups (P<0. 05) . The activity of AChE in cerebral cortex and hippocampus in the AlCl3 group was higher than that in the other groups (P<0. 05) . The activ⁃ ity of TBARS in cerebral cortex and hippocampus of AlCl3 group was higher than that of the other groups, while the activity of SOD, CAT and GSH was lower than that of the other groups (all P<0. 05) . The relative expression levels of inflammato⁃ ry cytokines TNFα, IL6, NFκB and COX2 mRNA in cerebral cortex and hippocampus in the AlCl3 group were higher than those in the other groups (all P<0. 05) . Conclusion UA can improve the cognitive function of AlCl3induced AD model rats, and its mechanism may be related to the decrease of aluminum content, AChE activity, oxidative stress level and the expression of inflammatory factors in cerebral cortex and hippocampus. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of early electroacupuncture intervention on the expression of TARDNA binding protein 43 (TDP- 43) and HMGB1/RhoA signaling pathway in the cerebral cortex of amyotrophic lateral sclerosis (ALS) mice, and to explore the potential mechanism of early electroacupuncture intervention in improving motor function in ALS mice. Method: SOD1G93A gene phenotype mice were randomly divided into model group (SOD1G93A ), acupuncture intervention group (EA), riluzole group (Riluzole), and SOD1G93A negative mice in the same litter were blank control group (Control), with 15 mice in each group. The electroacupuncture group was given acupuncture of Baihui point, bilateral Tianzhu point, bilateral Tianshu point, 5 times/7 days, 7 days for a course of treatment, a total of 4 courses of treatment. The riluzole group was treated with riluzole 30 mg（/ kg·d) by gavage, once a day, five times a week for two weeks. The motor function of mice in each group was evaluated by hind limb functional neurological score and rotarod fatigue test, and the rate of TDP-43 positive cells in cerebral cortex was observed by immunofluorescence. The relative expression of Iba-1, HMGB1 or RhoA protein in cerebral cortex was detected by Western Blot. The levels of serum TNF-α and MCP-1 were detected by Elisa. The morphological changes of cerebral cortical neurons were observed by transmission electron microscopy. Result: Compared with the control group, the rotarod latency time was decreased and the neurological score was increased in the model group (P<0.01) . The contents of serum MCP-1 and TNF-α, the expression of Iba1, HMGB1 and RhoA protein in cerebral cortex and the rate of TDP-43 positive cells were increased in the model group (P<0.01) . Compared with the model group, the rotarod latency time of the electroacupuncture group and the riluzole group increased and the neurological score decreased (P<0.01, P<0.05), the serum MCP-1, TNF-α content and the cerebral cortex Iba-1, HMGB1, RhoA protein expression and TDP-43 positive cell rate decreased (P<0.01, P<0.05) . The results of electron microscopy showed that the structure of cortical neurons in the control group was normal, and the nerve cells in the model group exhibited obvious pathological changes. The damage of nerve cells in the electroacupuncture group and the riluzole group was reduced, the structure was relatively complete, and some normal organelles were detected. Conclusion: Electroacupuncture intervention can improve the motor function of ALS model mice. The mechanism may be related to the inhibition of HMGB1/RhoA signaling pathway and the reduction of microglia-induced neuroinflammation, and it is speculated that it has a positive effect on the reduction of ALS pathological substrate TDP-43 deposition. [ABSTRACT FROM AUTHOR]

[Objectives]The paper aimed to investigate the specific mechanism through which isoflurane attenuated inflammation induced by microglia hyperactivation. [Methods]The microglia cells were treated by lipopolysaccharide(LPS)inducing inflammatory response in vitro, and the prepared emulsified isoflurane was used to treat to the cells. The effects of isoflurane and pathway protein inhibitors on the expression of pro-inflammatory mediators(pro-inflammatory factors, pro-inflammatory enzymes)and pathway proteins were detected by fluorescence quantitative PCR and Western blot, and then the effects of different inhibitors on protein expression and the signaling pathway of isoflurane action were determined. At the same time, the effects of different treatments on the translocation of nuclear factor κB(NF-κB)in microglia cells were observed. [Results]Compared with the control group, LPS significantly increased the expressions of interleukin(IL)-1β, IL-6, nitric oxide synthase(iNOS), cyclooxygenase-2(COXⅡ)and other pro-inflammatory factors, and up-regulated the expressions of target pathway protein and the translocation of NF-κB from cytoplasm to nucleus. Isoflurane reduced the expression of pro-inflammatory media and inhibited NF-κB nuclear translocation through CaMKⅡ/ERK/NF-κB signaling pathway. [Conclusions]Isoflurane reduced the release of proinflammatory factors and alleviated the inflammatory response of microglia cells through Ca2+ signaling pathway. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of transient receptor potential melatonin 2 (TRPM2) ion channels in microglia and astrocytes in temporal lobe epilepsy (TLE)-associated neuroinflammation. Methods Rats were randomly divided into the control group and epilepsy group. Seizure models were induced by lithium chloride-pilocarpine in the epilepsy group, and those in the control group were injected with the same dose of saline. The TLE rats were randomly divided into 7 subgroups according to the observation time after model establishment: acute phase (3 h group, 6 h group, 1 d group, 2 d group), latent phase (14 d group) and chronic phase (30 d group, 90 d group) subgroups (n = 5). The expression level of TRPM2 in the hippocampus of TLE rats at different stages were detected, and the cellular localization of TRPM2 in the brain of TLE rats was investigated. BV2 and C8 cell lines were induced by hydrogen peroxide (H2O2). The levels of IL1-β, IL-6 and TNF-α released by BV2 and C8 cells were observed by ELISA. The levels of TRPM2, poly (ADP-ribose) polymerase 1 (PARP-1), glycogen synthase kinase-3β(GSK-3β) and phosphorylated nuclear factor-κb p65 (p-NF-κb p65) were measured in H2O2-induced BV2 and C8 cells. Meantime, the activity of Calcineurin (CaN) in H2O2-induced BV2 was observed. Results The TRPM2 expression in 2d epileptic rat hippocampus was increased (P < 0.05). The expression of TRPM2 and the release of inflammatory cytokines were increased in H2O2 induced-BV2 and C8 cells (both P < 0.05). H2O2 could up-regulate the expression of PARP-1 and p-NF-κB p65 and enhance the activity of CaN in BV2 cells (all P < 0.05). Conclusions Oxidative stress can up-regulate the expression levels of TRPM2 and pro-inflammatory cytokines in microglia and astrocytes. Oxidative stress caused by recurrent epilepsy may mediate the occurrence of TLE-associated neuroinflammation through the TRPM2/ CaN/p-NF-κB p65 pathway in microglia. [ABSTRACT FROM AUTHOR]

Objective: To discuss the effect of rubusoside (RUB) on the spinal cord injury (SCI) and neuroinflammation in the mice, and to clarify its mechanism. Methods: A total of 48 female Kunming mice were randomly divided into sham operation group, SCI group, SCI+low dose of RUB group, and SCI+high dose of RUB group, and there were 12 mice in each group. Spinal cord injury behavior (BBB) scoring method was used to assess the motor function of the hind limbs of the SCI mice; water content method was used to detect the spinal cord edema of the SCI mice; real-time fluorscence quantitative PCR (RT-qPCR) method was used to detect the expression levels of pro-inflammatory cytokines cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) mRNA of the mice in various groups; ELISA method was used to detect the levels of inflammatory factors in serum of the mice in various groups; HE staining was used to observe the pathomorphology of spinal cord tissue of the mice in various groups；immunofluorescence was used to detect the activation of microglia in spinal cord tissue of the mice in various groups; Western blotting method was used to detect the expression levels of related proteins in spinal cord tissue of the mice in various groups. Results: The BBB score analysis results showed that compared with sham operation group, the score of the mice in SCI group was decreased to 0; compared with SCI group, the BBB scores of the mice in SCI+low dose of RUB group and SCI+high dose of RUB group were gradually increased. The spinal cord tissue water content detection results showed that compared with sham operation group, the water content in spinal cord tissue of the mice in SCI group was significantly increased (P<0. 01) ; compared with SCI group, the water contents in spinal cord tissue of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group were significantly decreased (P<0. 01) . The RT-qPCR results showed that compared with sham operation group, the expression levels of COX-2, IL-1β, and TNF-α mRNA in spinal cord tissue of the mice in SCI group were significantly increased (P<0. 001) . Compared with SCI group, the expression levels of COX-2, IL-1, and TNF- α mRNA in spinal cord tissue of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group were significantly decreased (P<0. 001). The ELISA results showed that compared with sham operation group, the levels of IL-1β (P<0. 01) and TNF-α (P<0. 001) in serum of the mice in SCI group were increased; compared with SCI group, the levels of IL-1β and TNF-α in spinal cord tissue of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group were decreased (P<0. 001). The Western blotting results showed that compared with sham operation group, the expression levels of nuclear factor kappa B (NF-κB) inhibitor protein-α (IκB-α), phosphorylated IκB-α (p-IκB-α), phosphorylated p65 (p-p65), p65, phosphorylated p38 (p-p38), phosphorylated extracellular regulated protein kinase (p-ERK), and phosphorylated c-Jun N-terminal kinase (p-JNK) proteins in spinal cord tissue of the mice in SCI group were significantly increased (P<0. 05 or P<0. 001) ; compared with SCI group, the expression levels of IκB- α, p-IκB- α, p-p65, p65, p-p38, p-ERK, and p-JNK proteins in spinal cord tissue of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group were significantly decreased (P<0. 001). The HE staining results showed that compared with sham operation group, the spinal cord tissue of the mice in SCI group had loose organization with the formation of vacuoles, and a large necrotic cavity was present in the center of the spinal cord; compared with SCI group, the central necrotic cavity area of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group was significantly decreased (P<0. 05). The immunofluorescence results showed that compared with sham operation group, the number of positive microglia cells in spinal cord tissue of the mice in SCI group was significantly increased (P<0. 001) ; compared with SCI group, the numbers of positive microglia cells in spinal cord tissue of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group were significantly decreased (P<0. 001). Conclusion: Rubusoside can improve the motor function impairment in the SCI mice, mitigate the neuroinflammation in spinal cord tissue, and inhibit the activation of microglia. The mechanism may be related to the downregulation of expression of proteins associated with the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways in spinal cord tissue. [ABSTRACT FROM AUTHOR]

Hyperbaric oxygen therapy characterized by fewer side effects and simple operation has been explored as a potential therapy for depression. This article provides a review of researches relevant to current clinical application and mechanism of hyperbaric oxygen therapy for depression， aiming to provide valuable references for the formulation of new strategies for the treatment of depression. Hyperbaric oxygen therapy has been demonstrated to be useful as an adjunctive therapy for depression， which can effectively alleviate depression by regulating the homeostasis of hypothalamus-pituitary-adrenal axis， inhibiting inflammation and enhancing synaptic plasticity. And hyperbaric oxygen therapy as adjuvant to antidepressants for depression can contribute to increasing the treatment effectiveness to some extent.

BackgroundEnvironmental noise pollution is serious, and there are few studies on the effects of long-term noise exposure during sleep on cognitive function and possible biological clock mechanism. ObjectiveTo explore the cognitive impairment induced by noise exposure during sleep in mice and possible biological clock mechanism, and to provide a theoretical basis for the protection against noise exposure. MethodsTwenty male C57BL/6J mice were randomly divided into a control group and a noise-exposed group, 10 mice in each group. The noise-exposed group was exposed to sleep-period noise using a noise generator for 12 h (08:00–20:00) per day for a total of 30 d. The calibrated noise intensity was set at 90 dB. No intervention was imposed on the control group. At the end of the noise exposure, cognitive function of mice was examined using the new object recognition experiment and the open field test, and the hippocampal tissue damage of mice were evaluated by Nissl staining, ionized calcium binding adaptor molecule 1 (Iba1) immunofluorescence staining, and real-time fluorescence quantitative PCR for inflammatory factors and biological clock genes. Oxidative stress indicators in the hippocampus of mice were also detected by assay kit. ResultsAfter noise exposure during sleep period, the results of new object recognition experiment showed that the discrimination index of mice in the noise-exposed group was 0.06±0.04, which was significantly lower than that of the control group (0.65±0.13) (P

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents, and its etiology and pathogenesis are still unclear. Brain is the organ with the largest oxygen consumption in human body and is easily affected by oxidative imbalance. Oxidative stress has become the key research direction for the pathogenesis of ADHD, but there is still a lack of relevant studies in China. Based on the latest research findings in China and overseas, this article reviews the clinical and experimental studies on oxidative stress in ADHD and explores the association of oxidative stress with neurotransmitter imbalance, neuroinflammation, and cell apoptosis in the pathogenesis of ADHD, so as to provide new research ideas for exploring the pathogenesis of ADHD. [ABSTRACT FROM AUTHOR]

nicotine on Poly (I∶C)-induced neuroinflammation and cognitive behavioral changes in mice. Objective To investigate the therapeutic effect of α7-nicotinic acetylcholine receptor (α7nAchR) agonist Methods Sixty female C57BL/6J mice were randomly divided into the normal control group, Poly (I∶C) group, nicotine group and α7nAchR antagonist group (MLA group), with 15 mice in each group. Mice in the model group were given Poly (I∶C)12 mg/kg through intraperitoneal injection to prepare the central nervous inflammation models. Mice in the nicotine group were intraperitoneally injected with 1 mg/kg nicotine 30 min before injection of Poly (I∶C). Mice in the MLA group were intraperitoneally injected with 5 mg/kg MLA 1 h before injection of Poly (I∶C) and 1 mg/kg nicotine 30 min before injection of Poly (I∶C). Mice in the model group and the normal control group were injected with the same amount of normal saline at the same time point. Three hours after modeling, 6 mice in each group were randomly selected for water maze experiment and open field experiment. The times of crossing the original platform, escape latency, average movement speed and distance of mice were recorded, so as to evaluate the spatial learning and memory ability and autonomous motor ability of mice. Three mice in each group were randomly selected to be killed, and brain tissues were collected. The activation of microglia in hippocampus and prefrontal cortex was observed by immunohistochemical method to evaluate the degree of central nervous inflammation in mice. The mRNA levels of IL-6, TNF-α, INF-β, INF-α and IL-1β were detected by qPCR, and the protein phosphorylation level of NF-κB p65 was detected by Western blotting. Results Compared with the normal control group, water maze test in the Poly (I∶C) group showed prolonged latency and reduced frequency of crossing the platform; open field test showed decreased mean motion speed and distance, increased activation of microglia in hippocampus and prefrontal lobe, increased expression levels of IL-6, TNF-α, INF-β, INF-α and IL-1β in the brain tissues, and increased level of NF-κB p65 phosphorylation in brain tissues (all P<0. 05). Compared with the Poly (I∶C) group, the water maze test in the nicotine group showed prolonged latency and increased frequency of crossing the platform, the open field test showed increased mean movement speed and distance, decreased activation of microglia in hippocampus and prefrontal lobe, and decreased expression levels of IL-6, TNF-α, INF-β, INF-α and IL-1β in the brain tissues, and decreased level of NF-κB p65 phosphorylation in brain (all P<0. 05). Compared with the nicotine group, the water maze test in the MLA group showed prolonged latency and decreased frequency of crossing the platform, the open field test showed decreased mean motion speed and distance, increased activation of microglia in hippocampus and prefrontal lobe, and increased expression levels of IL-6, TNF-α, INF-β, INF-α and IL-1β in the brain tissues, and increased level of NF-κB p65 phosphorylation in the brain tissues (all P<0. 05). Conclusion Nicotine can improve the neuroinflammation and cognitive behavioral changes induced by Poly (I∶C) in mice, and the mechanism is related to the reduction of NF-κB p65 phosphorylation through nicotine acting on α7nAchR, thus reducing the release of inflammatory factors. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease is a common neurodegenerative disease that seriously affects the quality of life of patients. At present, there is no effective targeted treatment. The pathogenesis of AD is complex and results from the combined effects of environmental, genetic and age factors. The typical pathological features of AD are the deposition of β-amyloid (Aβ), neurofibrillary tangles formed by hyperphosphorylation of microtubule-associated protein tau, and neuronal loss. A large number of studies have demonstrated that the aggregation of Aβ and tau proteins induces nucleotide-binding oligomerization domain-like receptors containing Pyrin-domain protein-3 (NLRP3) inflammasome activation, which is the core of the inflammatory mechanism of AD. Moreover, inhibitors and compounds targeting NLRP3 inflammasome and its upstream and downstream molecules can play a neuroprotective role in cells and animal models and improve spatial memory dysfunction, but clinical efficacy and safety remain to be studied. Therefore, inhibition of NLRP3 inflammasome activation may be a potential therapeutic target for AD. In this paper, the activation mechanism and influencing factors of NLRP3 inflammasome as well as its relationship with AD are reviewed, and the therapeutic drugs targeting NLRP3 inflammasome for AD are summarized in order to provide a new direction for NLRP3 inflammasome related diseases such as AD. [ABSTRACT FROM AUTHOR]