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Background: Artificial intelligence (AI) technology is a promising diagnostic adjunct in fracture detection. However, few studies describe the improvement of clinicians' diagnostic accuracy for nasal bone fractures with the aid of AI technology.Objective: This study aims to determine the value of the AI model in improving the diagnostic accuracy for nasal bone fractures compared with manual reading.Methods: A total of 252 consecutive patients who had undergone facial computed tomography (CT) between January 2020 and January 2021 were enrolled in this study. The presence or absence of a nasal bone fracture was determined by two experienced radiologists. An AI algorithm based on the deep-learning algorithm was engineered, trained and validated to detect fractures on CT images. Twenty readers with various experience were invited to read CT images with or without AI. The accuracy, sensitivity and specificity with the aid of the AI model were calculated by the readers.Results: The deep-learning AI model had 84.78% sensitivity, 86.67% specificity, 0.857 area under the curve (AUC) and a 0.714 Youden index in identifying nasal bone fractures. For all readers, regardless of experience, AI-aided reading had higher sensitivity ([94.00 ± 3.17]% vs [83.52 ± 10.16]%, P< 0.001), specificity ([89.75 ± 6.15]% vs [77.55 ± 11.38]%, P< 0.001) and AUC (0.92 ± 0.04 vs 0.81 ± 0.10, P< 0.001) compared with reading without AI. With the aid of AI, the sensitivity, specificity and AUC were significantly improved in readers with 1-5 years or 6-10 years of experience (all P< 0.05, Table 4). For readers with 11-15 years of experience, no evidence suggested that AI could improve sensitivity and AUC (P= 0.124 and 0.152, respectively).Conclusion: The AI model might aid less experienced physicians and radiologists in improving their diagnostic performance for the localisation of nasal bone fractures on CT images. [ABSTRACT FROM AUTHOR]

Abstract: Tumor necrosis factor alpha (TNF-α) is implicated in the development of persistent pain. Its expression increases both spinally and supraspinally after peripheral inflammation. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Prefrontal synaptic transmission is potentiated in mice with chronic pain through an enhancement of presynaptic transmitter release. However, it is not known if TNF-α expression is altered in the ACC in response to persistent pain and if synaptic transmission within this region is modulated by TNF-α. In the present study, we examined TNF-α expression in the mouse ACC following hind-paw administration of complete Freund''s adjuvant (CFA) and examined the role of TNF-α in ACC synaptic transmission. Quantification of TNF-α at the protein level (by ELISA) revealed enhanced expression following CFA-induced peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that TNF-α significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC. Our findings provide evidence that presynaptic alterations caused by peripheral inflammation is partly attributable to the up-regulation of TNF-α in the ACC. [Copyright &y& Elsevier]

Background: The use of nonintubated video-assisted thoracoscopic surgery (NI-VATS) has been increasingly reported to yield favourable outcomes. However, this technology has not been routinely used because its advantages and safety have not been fully confirmed. The aim of this study was to assess the safety and feasibility of nonintubated spontaneous ventilation (NI-SV) anesthesia compared to intubated mechanical ventilation (I-MV) anesthesia in VATS by evaluating of perioperative complications and practitioners' workloads. Methods: Patients who underwent uniportal VATS were randomly assigned at a 1:1 ratio to receive NI-SV or I-MV anesthesia. The primary outcome was the occurrence of intraoperative airway intervention events, including transient MV, conversion to intubation and repositioning of the double-lumen tube. The secondary outcomes included perioperative complications and modified National Aeronautics and Space Administration Task Load Index (NASA-TLX) scores from anesthesiologists and surgeons. Results: Thirty-five patients in each group were enrolled in the intention-to-treat analysis. The incidence of intraoperative airway intervention events was greater in the NI-SV group than in the I-MV group (12 [34.3%] vs. 3 [8.6%]; OR = 0.180; 95% CI = 0.045–0.710; p = 0.009). No significant difference was found in the postoperative pulmonary complications between the groups (p > 0.05). The median of the anesthesiologists' overall NASA-TLX score was 37.5 (29–52) when administering the NI-SV, which was greater than the 25 (19-34.5) when the I-MV was administered (p < 0.001). The surgeons' overall NASA-TLX score was comparable between the two ventilation strategies (28 [21-38.5] vs. 27 [20.5–38.5], p = 0.814). Conclusion: The NI-SV anesthesia was feasible for VATS in the selected patients, with a greater incidence of intraoperative airway intervention events than I-MV anesthesia, and with more surgical effort required by anesthesiologists. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200055427. https://www.chictr.org.cn/showproj.html?proj=147872 was registered on January 09, 2022. [ABSTRACT FROM AUTHOR]

Puerarin 6″‐O‐xyloside is a tumor suppressive derivate of Puerarin that is recently characterized as a lysine‐specific demethylase 6B inhibitor. Here we investigated the effects of Puerarin 6″‐O‐xyloside in hepatocellular carcinoma (HCC) cell lines SMMC‐7721 and HepG2. Cell viability, proliferation, stemness, protein expression, and autophagy were tested by CCK‐8, colony formation, sphere formation, western blotting, and LC3B GFP puncta per cell, respectively. Apoptosis, CD133‐positive cells, and JC‐1‐labeled mitochondrial membrane potential were measured by flow cytometry. The effects of Puerarin 6″‐O‐xyloside in vivo were explored in HepG2 xenograft mice. Puerarin 6″‐O‐xyloside inhibited cell viability, proliferation, and stemness, and promoted apoptosis in both SMMC‐7721 and HepG2 cells. Further experiments showed promoted autophagy and decreased mitochondrial membrane potential, and decreased expression of p‐PI3K, p‐AKT, and p‐mTOR in HepG2 cells. Co‐administration of 3‐MA with Puerarin 6″‐O‐xyloside obviously augmented these effects including inhibited protein expression of p‐PI3K, p‐AKT, and p‐mTOR, and inhibited proliferation, promoted apoptosis, and decreased stemness. In HepG2 xenograft mice, 100 mg/kg/d Puerarin 6″‐O‐xyloside significantly suppressed tumor growth, stemness, and apoptosis. In conclusion, our study indicated that Puerarin 6″‐O‐xyloside decreased cell viability, proliferation, and stemness, and promoted autophagy and mitochondria‐dependent apoptosis of HCC, at least partly through inhibiting PI3K/AKT/mTOR. These results highlighted Puerarin 6″‐O‐xyloside as a promising prodrug that could inhibit both PI3K/AKT/mTOR and epigenetic demethylation. [ABSTRACT FROM AUTHOR]

The anterior clinoid process (ACP) is surrounded by nerves and vessels that, together, constitute an intricate anatomical structure with variations that challenges the performance of individualized anterior clinoidectomy in treating lesions with different extents of invasion. In the present study, we established a 6-surface system for the ACP based on anatomical landmarks and analyzed its value in guiding ACP drilling and resection of paraclinoid meningiomas. Using the anatomical characteristics of 10 dry skull specimens, we set 9 anatomical landmarks to delineate the ACP into 6 surfaces. Guided by our 6-surface system and eggshell technique, 5 colored silicone-injected anatomical specimens were dissected via a frontotemporal craniotomy to perform anterior clinoidectomy. Next, 3 typical cases of paraclinoid meningioma were selected to determine the value of using our 6-surface system in tumor resection. Nine points (A–H and T) were proposed to delineate the ACP surface into frontal, temporal, optic nerve, internal carotid artery, cranial nerve III, and optic strut surfaces according to the adjacent tissues. Either intradurally or extradurally, the frontal and temporal surfaces could be identified and drilled into depth, followed by skeletonization of the optic nerve, cranial nerve III, internal carotid artery, and optic strut surfaces. After the residual bone was removed, the ACP was drilled off. In surgery of paraclinoid meningiomas, our 6-surface system provided great benefit in locating the dura, nerves, and vessels, thus, increasing the safety of opening the optic canal and relaxing the oculomotor or optic nerves and allowing for individualized ACP drilling for meningioma removal. Our 6-surface system adds much anatomical information to the classic Dolenc triangle and can help neurosurgeons, especially junior ones, to increase their understanding of the paraclinoid spatial structure and accomplish individualized surgical procedures with high safety and minimal invasiveness. [ABSTRACT FROM AUTHOR]

Abstract: The recently developed induced pluripotent stem cell (iPSC) technique provides new direction for vaccination: somatic cells can be induced into iPSCs and expanded, then the cells are genetically or chemically promoted to a immune cell fate, followed with in vitro antigen presenting and processing processes to produce memory B cells that can secret functional antibodies to different pathogens; finally these cells are transplanted back to human. [Copyright &y& Elsevier]

Background and Purpose: The endocannabinoid (eCB) system is involved in pathways that regulate drug addiction and eCB-mediated synaptic plasticity has been linked with addictive behaviours. Here, we investigated the molecular mechanisms underlying the changes in eCB-dependent synaptic plasticity in the nucleus accumbens core (NAcc) following short-term withdrawal from repeated morphine treatment.Experimental Approach: Conditioned place preference (CPP) was used to evaluate the rewarding effects of morphine in rats. Evoked inhibitory postsynaptic currents of medium spiny neurons in NAcc were measured using whole-cell patch-clamp recordings. Changes in depolarization-induced suppression of inhibition (DSI) in the NAcc were assessed to determine the effect of short-term morphine withdrawal on the eCB system. To identify the potential modulation mechanism of short-term morphine withdrawal on the eCB system, the expression of diacylglycerol lipase α (DGL-α) and monoacylglycerol lipase was detected by Western blot analysis.Key Results: Repeated morphine administration for 7 days induced stable CPP. Compared with the saline group, the level of DSI in the NAcc was significantly increased in rats after short-term morphine withdrawal. Furthermore, this increase in DSI coincided with a significant increase in the expression of DGL-α.Conclusions and Implications: Short-term morphine withdrawal potentiates eCB modulation of inhibitory synaptic transmission in the NAcc. We also found that DGL-α expression was elevated after short-term morphine withdrawal, suggesting that the eCB 2-arachidonyl-glycerol but not anandamide mediates the increase in DSI. These findings provide useful insights into the mechanisms underlying eCB-mediated plasticity in the NAcc during drug addiction.Linked Articles: This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc. [ABSTRACT FROM AUTHOR]

Purpose: Endometriosis is a common chronic gynecological disease greatly affecting women health. Prior studies have implicated that dysferlin (DYSF) aberration might be involved in the pathogenesis of ovarian endometriosis. In the present study, we explore the potential presence of DYSF mutations in a total of 152 Han Chinese samples with ovarian endometriosis. Methods: We analyze the potential presence of DYSF mutations by direct DNA sequencing. Results: A total of seven rare variants/mutations in the DYSF gene in 10 out of 152 samples (6.6%) were identified, including 5 rare variants and 2 novel mutations. For the 5 rare variants, p.R334W and p.G941S existed in 2 samples, p.R865W, p.R1173H and p.G1531S existed in single sample, respectively; for the two novel mutations, p.W352* and p.I1642F, they were identified in three patients. These rare variants/mutations were absent or existed at extremely low frequency either in our 1006 local control women without endometriosis, or in the China Metabolic Analytics Project (ChinaMAP) and Genome Aggregation Database (gnomAD) databases. Evolutionary conservation analysis results suggested that all of these rare variants/mutations were evolutionarily conserved among 11 vertebrate species from Human to Fox. Furthermore, in silico analysis results suggested these rare variants/mutations were disease-causing. Nevertheless, we find no significant association between DYSF rare variants/mutations and the clinical features in our patients. To our knowledge, this is the first report revealing frequent DYSF mutations in ovarian endometriosis. Conclusion: We identified a high frequency of DYSF rare variants/mutations in ovarian endometriosis for the first time. This study suggests a new correlation between DYSF rare variants/mutations and ovarian endometriosis, implicating DYSF rare variants/mutations might be positively involved in the pathogenesis of ovarian endometriosis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the efficacy of Fluoro Jade-C staining (FJC) in the assessment of brain injury after deep hypothermia circulatory arrest (DHCA). Methods: Six healthy adult miniature male pigs underwent DHCA, the rectal temperature was down to 18°C, circulation was stopped , circulatory arrest was maintained for 60 minutes. On postoperative day 1, perfusion-fixation was performed on brain tissue. Cerebral cortex, hippocampus, cerebellum were taken for sampling. FJC, hematoxylin–eosin staining (HE), nissl staining (NISSL), terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) were performed to detect the histological and pathological changes. Histological scores of all slices were ranked. Comparison between the FJC and other techniques was done by analysis of variance (ANOVA) according to histological scores. Results: All animals survived the operation. On the cerebral cortex, in comparison of FJC between HE, NISSL and TUNEL, the p value was 0.90, 0.40, 0.16 respectively (p >0.05). On the hippocampus, the comparison of FJC with HE, NISSL and TUNEL had a p value of 0.12, 0.23, 0.62 respectively (p >0.05). On the cerebellum, in comparing FJC with HE, NISSL and TUNEL, the p value was 0.96, 0.77, 0.96 respectively (p >0.05). On representative regions, the results of FJC were in accordance with that of TUNEL, NISSL and HE. Furthermore, ascertainment of brain injury is easier with FJC. Conclusion: FJC is a reliable and convenient method to assess brain injury after DHCA. [ABSTRACT FROM AUTHOR]

Abnormal oscillation in the cortical-basal ganglia loop is involved in the pathophysiology of parkinsonism. High-voltage spindles (HVSs), one of the main type abnormal oscillations in Parkinson’s disease, are regulated by dopamine D2-like receptors but not D1-like receptors. However, little is known about how dopamine D2-like receptors regulate HVSs and the role of hyperpolarization-activated cyclic nucleotide-gated2 (HCN2) in HVSs regulation. We simultaneously recorded the local field potential (LFP) in globus pallidus (GP) and electrocorticogram (ECoG) in primary motor cortex (M1) in freely moving 6-hydroxydopamine (6-OHDA) lesioned or control rats. The expression of HCN2 and dopamine D2 receptor in the subthalamic nucleus (STN) was examined by immunochemical staining and Western blotting. We also tested the role of HCN2 in HVSs regulation by using pharmacological and shRNA methodology. We found that dopamine D2-like receptor agonists suppressed the increased HVSs in 6-OHDA lesioned rats. HCN2 was co-expressed with dopamine D2 receptor in the STN, and dopamine depletion decreased the expression of HCN2 as well as dopamine D2 receptor which contribute to the regulation of HVSs. HCN2 was down regulated by HCN2 shRNA, which thereby led to an increase in the HVSs in naïve rats while HCN2 agonist reduced the HVSs in 6-OHDA lesioned rats. These results suggest that HCN2 in the STN is involved in abnormal oscillation regulation between M1 cortex and GP. [ABSTRACT FROM AUTHOR]

Many studies showed that abnormal oscillations in the cortical-basal ganglia loop is involved in the pathophysiology of Parkinson’s disease (PD). In contrast to the well-studied beta synchronization, high-voltage spindles (HVSs), another type of abnormal oscillation observed in PD, are neglected. To explore the role of subthalamic nucleus-deep brain stimulation (STN-DBS) in HVSs regulation, we simultaneously recorded the local field potential (LFP) in the globus pallidus (GP) and electrocorticogram (ECoG) in the primary motor cortex(M1) in freely moving 6-hydroxydopamine (6-OHDA) lesioned or control rats before, during, and after STN-DBS. Consistent with our previous study, HVSs occurrence, duration, and relative power and coherence between the M1 cortex and GP increased in 6-OHDA lesioned rats. We found that high but not low frequency stimulation restored the abnormal HVSs activity and motor deficit. These results suggest that the STN is involved in the abnormal oscillation between the M1 cortex and GP. [ABSTRACT FROM AUTHOR]

Purpose: Non-human primate models of deep brain stimulation (DBS) play an increasingly important role in the exploration of DBS mechanisms. The establishment and recognized usefulness of such models depend on the precise positioning of the stimulating targets and electrode implants. The optimal method of targeting remains controversial. Materials and methods: This paper described an improved stereotactic procedure that uses a self-developed adaptor to improve accuracy. This involved: (1) connecting clinical stereotactic devices with the skull of primates using a self-developed adaptor; (2) pre-operation targeting via magnetic resonance imaging (MRI); (3) target re-checking by microelectrode recording (MER); (4) DBS electrode implantation; (5) post-operative MRI verification of electrode placement and (6) positioning confirmation by DBS programming. Results: Use of the adaptor enabled clinical stereotactic surgery, pre-operative MRI targeting, microelectrode mapping and post-operative verification in primate DBS operations. Discrepancies between achieved and predetermined electrode position were around 0.6 mm. DBS programming improved the motor function of the hemiparkinsonism animals and decreased the numbers of rotation induced by apomorphine, indicating the precise positioning of the stimulating target and successful implanting of electrode using this method. Conclusions: An improved stereotactic procedure was performed during a non-human primate DBS operation using a self-developed adaptor. The accuracy of DBS electrode implantation in non-human primates was improved with this method. [ABSTRACT FROM AUTHOR]

Astrocytoma is the most common primary brain tumor and it is associated with poor prognosis. Accumulating evidences suggest that certain molecular abnormalities or genetic mutations are associated with its progression and prognosis. Human transcriptional coactivator 4 (PC4), originally identified as a transcriptional coactivator then as a DNA replication and repair factor has been shown to be involved in chromatin organization. Recently, it is reported to function both as tumor suppressor and promoter depending on the cellular settings. In the present study, we for the first time demonstrated that the expression of PC4 in astrocytoma was upregulated as assessed by western blot and immunohistochemical staining. Moreover, elevated PC4 expression was strongly correlated with the progression of astrocytoma. Furthermore, high PC4 expression was also associated with poor overall survival. Finally, in vitro study demonstrated that siRNA mediated PC4 downregulation significantly inhibited the proliferation and invasiveness of human glioma cells. These results suggested that PC4 might play a role in human astrocytoma progression and may be used as a novel indicator for the prognosis of astrocytoma patient. [ABSTRACT FROM AUTHOR]

The function of TRPV1 (transient receptor potential vanilloid subfamily, member 1) in the central nervous system is gradually elucidated. It has been recently proved to be expressed in nucleus accumbens (NAc), a region playing an essential role in mediating opioid craving and taking behaviors. Based on the general role of TRPV1 antagonist in blocking neural over-excitability by both pre- and post-synaptic mechanisms, TRPV1 antagonist capsazepine (CPZ) was tested for its ability to prohibit persistent opioid craving in rats. In the present study, we assessed the expression of TRPV1 in nucleus accumbens and investigated the effect of CPZ in bilateral nucleus accumbens on persistent morphine conditioned place preference (mCPP) in rats. We also evaluated the side-effect of CPZ on activity by comparing cross-beam times between groups. We found that morphine conditioned place preference increased the TRPV1 expression and CPZ attenuated morphine conditioned place preference in a dose-dependent and target–specific manner after both short- and long-term spontaneous withdrawal, reflected by the reduction of the increased time in morphine-paired side. CPZ (10 nM) could induce prolonged and stable inhibition of morphine conditioned place preference expression. More importantly, CPZ did not cause dysfunction of activity in the subjects tested, which indicates the inhibitory effect was not obtained at the sacrifice of regular movement. Collectively, these results indicated that injection of TRPV1 antagonist in nucleus accumbens is capable of attenuating persistent morphine conditioned place preference without affecting normal activity. Thus, TRPV1 antagonist is one of the promising therapeutic drugs for the treatment of opioid addiction. [ABSTRACT FROM AUTHOR]

Highlights: [•] 6-OHDA could alter membrane properties in SNc DA neurons. [•] Cav2.2 may be involved in the 6-OHDA-induced oxidative stress. [•] PKA plays a key role on 6-OHDA-induced Ca2+ entry. [Copyright &y& Elsevier]

The vesicular glutamate transporters, VGLUT1 and VGLUT2, reportedly display complementary distribution in the rat brain. However, co-expression of them in single neurons has been reported in some brain areas. We previously found co-expression of VGLUT1 and VGLUT2 mRNAs in a number of single neurons in the principal sensory trigeminal nucleus (Vp) of the adult rat; the majority of these neurons sent their axons to the thalamic regions around the posteromedial ventral nucleus (VPM) and the posterior nuclei (Po). It is well known that trigeminothalamic (T-T) projection fibers arise not only from the Vp but also from the spinal trigeminal nucleus (Vsp), and that trigeminocerebellar (T-C) projection fibers take their origins from both of the Vp and Vsp. Thus, in the present study, we examined the expression of VGLUT1 and VGLUT2 in Vp and Vsp neurons that sent their axons to the VPM/Po regions or the cortical regions of the cerebellum. For this purpose, we combined fluorescence in situ hybridization (FISH) histochemistry with retrograde tract-tracing; immunofluorescence histochemistry was also combined with anterograde tract-tracing. The results indicate that glutamatergic Vsp neurons sending their axons to the cerebellar cortical regions mainly express VGLUT1, whereas glutamatergic Vsp neurons sending their axons to the thalamic regions express VGLUT2. The present data, in combination with those of our previous study, indicate that glutamatergic Vp neurons projecting to the cerebellar cortical regions express mainly VGLUT1, whereas the majority of glutamatergic Vp neurons projecting to the thalamus co-express VGLUT1 and VGLUT2. [ABSTRACT FROM AUTHOR]

Abstract: Relapse is a major clinical problem and remains a major challenge in the treatment of drug addiction. There is strong evidence that the endocannabinoid system of the nucleus accumben core (NAcc) is involved in drug-seeking behavior, as well as in the mechanisms that underlie relapse to drug use. To reveal the mechanism that underlies this finding, we examined the expression pattern of the cannabinoid receptor 1 (CB1-R) in the NAcc of SD rats that had been undergoing morphine withdrawal (MW) for 1 day, 3 days and 3 weeks (acute, latent and chronic phases, respectively). Morphine exposure induced conditioned place preference (CPP) in rats. Significant increase of CB1-R expression in NAcc was observed in animals in the 1 day, 3 days and 3 weeks morphine withdrawal compare to the control group. Immunofluorescence labeling showed axonal fibers or terminals by fluorescence microscope observation. Immunoelectron microscopy detection showed silver-gold particles located in the presynaptic membranes that mainly give rise to symmetrical synapses. Quantitative electron microscopy showed an increase in number of CB1-R-positive terminals in the morphine withdrawal groups and the number of immunogold particles was significantly increased at these inhibitory terminals. We also confirmed that infusions of the CB1-R antagonist rimonabant into the NAcc attenuated the CPP during morphine withdrawal. Our present data have thus indicated that increasing pattern of CB1-R expression in the NAcc during above morphine withdrawal phases, which might underlie the relapse associated drug seeking behavior after morphine withdrawal. [Copyright &y& Elsevier]

Abstract: Cerebral edema is a critical complication after intravascular thrombolysis post-acute stroke. However, clinical options remained limited for treating cerebral edema after cerebral ischemia/reperfusion (I/R) injury. In the present study, astragaloside IV, a purified extract from astragalus membranaceus, was used in the focal I/R rat model, aimed to investigate its effect on the cerebral edema. We found that astragaloside IV (10 and 20mg/kg) significantly attenuated the cerebral water content (P<0.05) and improved neurological outcomes (P<0.05) in comparison with vehicle group. Moreover, we investigate the effect of astragaloside IV on the (blood–brain barrier) BBB since cerebral edema was closely related to the permeability of the BBB. We found that the permeability of BBB was improved significantly in astragaloside IV groups compared with vehicle group via Evans blue leakage (P<0.05). This was further confirmed under the electron microscope, using lanthanum as a tracer of blood vessel permeability. Lanthanum was usually found within the blood vessel in sham group, rather than in perivascular tissues as shown in vehicle group. In drug groups, lanthanum stain was mainly restricted within the cerebral capillary, indicating the potential BBB-protective effect of astragaloside IV. Furthermore, we found that expressions of Matrix metalloproteinase-9 (MMP-9) and aquaporin 4 (AQP4) were increased in vehicle group, which were related to cerebral vasogenic edema or cytotoxic edema. The up-regulations of MMP-9 and AQP4 were inhibited significantly by astragaloside IV administration. We propose that the anti-edema potential of astragaloside IV was correlated with its regulation of MMP-9 and AQP4. [Copyright &y& Elsevier]

High-voltage spindles (HVSs) have been reported to appear spontaneously and widely in the cortical–basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP) and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D1-like receptors or D2-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1) in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D2-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D2-like receptor antagonists. On the contrary, the selective dopamine D1-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D2-like receptors, but not D1-like receptors, were involved in HVS regulation. This supports the important role of dopamine D2-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion. [ABSTRACT FROM AUTHOR]

The chronic mild stress (CMS) protocol is widely used to evoke depression-like behaviors in the laboratory. Some animals exposed to CMS are resistant to the development of anhedonia, whereas the remaining are responsive, CMS-resilient and CMS-sensitive, respectively. The aim of this study was to examine the effects of chronic stress on oxidative parameters in the rat brain. The consumption of sweet food, protein and lipid oxidation levels and superoxide dismutase and catalase activities in the rat hippocampus, cortex and cerebellum were assessed. We found a significant increase in protein peroxidation (hippocampus and cortex), a significant increase in catalase activity (cortex, hippocampus and cerebellum) and a decrease in superoxide dismutase activity (cortex, hippocampus and cerebellum) in the CMS-sensitive group compared to the CMS-resilient group and normal controls as well as an increase in lipid peroxidation (cerebellum) in the CMS-sensitive and CMS-resilient groups compared to normal controls. However, there was no significant difference in protein peroxidation (cerebellum) and lipid peroxidation (cortex and hippocampus) among the three groups. In conclusion, our results indicate that the segregation into CMS-sensitive and -resilient groups based on sucrose intake is paralleled by significant differences in oxidative parameters. CMS induces oxidative damage and alterations in the activity of antioxidants which may lead to increased oxidative damage, irrespective of the anhedonia-like status of the stressed animals. [ABSTRACT FROM AUTHOR]

This study evaluated the role of gastrocnemius-derived brain-derived neurotrophic factor (BDNF) and possible mechanism in motor improvement in T10 spinal cord transection (SCT) rats. There was complete paralysis in hindlimbs immediately after SCT, followed by partial functional restoration with time going. The level of BDNF but not its mRNA gradually increased in caudal stump after SCT, whereas a significant increase in both BDNF and its mRNA was simultaneously seen in gastrocnemius. Injection of BDNF antibody into the gastrocnemius significantly decreased hindlimb locomotor function, downregulated the level of BDNF and its mRNA together with extracellular signal-regulated kinase 1/2 (Erk1/2). Moreover, ventral root ligation led to decrease both BDNF and Erk in caudal stump, indicating BDNF transportation from gastrocnemius into the spinal cord. We concluded that gastrocnemius-derived BDNF reduced motor functional deficits in SCT rats through Erk signaling pathway. These novel findings suggested the usage of BDNF in muscle for the treatment of spinal cord injury in clinic. [ABSTRACT FROM AUTHOR]

Oscillation activities are the feature of neural network and correlated to different physiological states. The theta ( θ) oscillation (2-7 Hz) has been reported in the basal ganglia, and the intrinsic resonance properties of individual neurons have provided a basis for this network oscillation. The basal ganglia neurons receive comprehensive modulation arising from dopaminergic (DA) neurons located in the substantia nigra pars compacta (SNc), but how the oscillation is regulated in SNc DA neurons remains poorly understood. In this paper, whole-cell patch-clamp recordings were performed on SNc DA neurons in rat brain slices to reveal the resonance properties and underlying mechanisms. After swept-sine-wave (ZAP protocol) current was injected into SNc DA neurons, θ resonance was induced, whose peak impedance went up with the rising of temperature, demonstrating the dependency of resonance on temperature. Voltage dependency of resonance was also observed at hyperpolarized membrane potentials. Further investigation demonstrated two individual components: (1) SK-current generated resonance at around −65 mV, which could be blocked by apamin (300 nM), a specific antagonist of the small-conductance calcium-dependent potassium channel; (2) h-current ( I) generated resonance at around −75 mV, which could be abolished by ZD7288 (10 μM), a selective blocker of HCN channels. We concluded that in SNc DA neurons, θ resonance was mediated by two distinct ionic channels at hyperpolarized potentials. Our results imply that θ frequency resonance of individual SNc DA neurons may participate in coordinating rhythmic firing activity and contribute to the physiological or pathophysiological behaviors of Parkinson's disease. [ABSTRACT FROM AUTHOR]

Abstract: The oscillatory activity in the basal ganglia is believed to have an important function, but little is known about its actual mechanisms. We studied the resonance characteristics of subthalamic nucleus (STN) neurons and their ionic mechanisms using whole-cell patch-clamp recordings in rat brain slices. A swept-sine-wave current with constant amplitude and linearly increasing frequency was applied to measure the resonance frequency (f res) of STN neurons. We also used single-frequency sine wave current to evoke firing. We found that the resonance of STN neurons was temperature- and voltage-dependent. The f res of STN neurons was about 4Hz when the temperature was maintained at 38°C and holding potential was at −70mV. The f res increased with more negative holding potentials and decreased with lower temperature. Action potentials fired most readily when the input frequency was near f res. After application of drug ZD7288 (20μM), the resonance of STN neurons was blocked and the spikes evoked by both impedance amplitude profile (ZAP) current and single-frequency sine wave current arose readily at the lowest frequencies, indicating that hyperpolarization-activated cation current (I h) generated the resonance and mediated a preferential coupling at frequencies near f res between inputs and firing. In conclusion, there is a θ-frequency resonance mediated by I h in STN neurons. The resonance characteristics are temperature- and voltage-dependent. The resonance mediates a frequency-selective coupling between inputs and firing. [Copyright &y& Elsevier]

Background: Fragile X syndrome (FXS) is caused by the absence of the mRNA-binding protein Fragile X mental retardation protein (FMRP), encoded by the Fmr1 gene. Overactive signaling by group 1 metabotropic glutamate receptor (Grp1 mGluR) could contribute to slowed synaptic development and other symptoms of FXS. Our previous study has identified that facilitation of synaptic long-term potentiation (LTP) by D1 receptor is impaired in Fmr1 knockout (KO) mice. However, the contribution of Grp1 mGluR to the facilitation of synaptic plasticity by D1 receptor stimulation in the prefrontal cortex has been less extensively studied. Results: Here we demonstrated that DL-AP3, a Grp1 mGluR antagonist, rescued LTP facilitation by D1 receptor agonist SKF81297 in Fmr1KO mice. Grp1 mGluR inhibition restored the GluR1-subtype AMPA receptors surface insertion by D1 activation in the cultured Fmr1KO neurons. Simultaneous treatment of Grp1 mGluR antagonist with D1 agonist recovered the D1 receptor signaling by reversing the subcellular redistribution of G protein-coupled receptor kinase 2 (GRK2) in the Fmr1KO neurons. Treatment of SKF81297 alone failed to increase the phosphorylation of NR2B-containing N-methyl D-aspartate receptors (NMDARs) at Tyr-1472 (p-NR2B-Tyr1472) in the cultures from KO mice. However, simultaneous treatment of DL-AP3 could rescue the level of p-NR2B-Tyr1472 by SKF81297 in the cultures from KO mice. Furthermore, behavioral tests indicated that simultaneous treatment of Grp1 mGluR antagonist with D1 agonist inhibited hyperactivity and improved the learning ability in the Fmr1KO mice. Conclusion: The findings demonstrate that mGluR1 inhibition is a useful strategy to recover D1 receptor signaling in the Fmr1KO mice, and combination of Grp1 mGluR antagonist and D1 agonist is a potential drug therapy for the FXS. [ABSTRACT FROM AUTHOR]

Abstract: Major vault protein (MVP) is a vesicular drug transporter and may participate in multidrug resistance (MDR). The aim of this study was to determine the expression and cellular localization of MVP in refractory frontal lobe epilepsy (FLE). We detected MVP expression in tissue samples from the refractory frontal cortex of 30 patients who had been surgically treated for refractory epilepsy. We compared these tissues with twelve histologically normal frontal lobe samples from controls. In the control group, the expression of MVP was faint in the cortex. The expression of MVP protein increased dramatically in the refractory epilepsy group; MVP immunoreactivity (IR) was observed in the cytoplasm of neurons. Thus, MVP protein was increased in the frontal cortex of patients with refractory epilepsy. Further research is necessary to determine whether or not MVP plays a role in the mechanisms underlying drug resistance in refractory FLE. [Copyright &y& Elsevier]

Abstract: Epilepsy is a chronic neurological disorder characterized by spontaneous recurrent seizures, which also occur in demyelinating diseases of the central nervous system (CNS) with a higher prevalence. Meanwhile, demyelination occurrings have been occasionally observed in CNS of epilepsy patients, indicating an association between demyelination and epileptic seizures by an unknown mechanism. However, no confirmative experimental evidence has yet been given. Thus, by using a rat pentylenetetrazol model, electroencephalogram (EEG), Western blotting, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, the present study provided direct evidence that myelin sheath damage in rat hippocampus and cerebral cortex started in the early stage of epileptic seizures induction and lasted with no further increase in severity in the development of epileptic seizures. It was illustrated that myelin sheath damage was not the result of oligodendrocyte destruction, but the autoantibodies against myelin basic protein (MBP) produced in peripheral circulation accompanied by increased permeability of blood–brain barrier (BBB) formed in the development of epileptic seizures. This study firstly provided experimental evidence for myelin sheath damage in PTZ-induced rat''s epileptic seizures and further demonstrated that its possible cause was autoimmunoreaction. [Copyright &y& Elsevier]

Abstract: Oxidative injury has been implicated in the etiology of Parkinson''s disease (PD). Gypenosides (GPs), the saponins extract derived from the Gynostemma pentaphyllum, has various bioactivities. In this study, GPs was investigated for its neuroprotective effects on the 1-methyl-4-phenylpyridinium ion (MPP+)-induced oxidative injury of dopaminergic neurons in primary nigral culture. It was found that GPs pretreatment, cotreatment or posttreatment significantly and dose-dependently attenuated MPP+-induced oxidative damage, reduction of dopamine uptake, loss of tyrosine hydrolase (TH)-immunopositive neurons and degeneration of TH-immunopositive neurites. However, the preventive effect of GPs was more potential than its therapeutical effect. Most importantly, the neuroprotective effect of GPs may be attributed to GPs-induced strengthened antioxidation as manifested by significantly increased glutathione content and enhanced activity of glutathione peroxidase, catalyze and superoxide dismutase in nigral culture. The neuroprotective effects of GPs are specific for dopaminergic neurons and it may have therapeutic potential in the treatment of PD. [Copyright &y& Elsevier]

Abstract: We studied the effect of stereotactic surgery in cases of alcohol dependence. Twelve patients with a psychological dependence on alcohol (treated systematically with medication for detoxification 3–8 times in various rehabilitation centers before, but had relapsed within 2 weeks after withdrawal) were treated by ablating the nucleus accumbens (NAC) bilaterally using stereotactic surgery. The therapeutic effect and safety evaluation index of the surgery were analyzed. The timing of the conducted evaluations was preoperatively and in the sixth postoperative month. Currently, relapse has not occurred in 9 cases. Relapse occurred in 3 cases after surgery. The prevalence of relapse was 16.7% within 6 months, and 25% within 12 months. Non-specific complications of this type of surgery (e.g., intracranial hematoma, infection) were not observed. One case in 12 patients suffered dysosmia, but he recovered completely 4 months later after surgery. The full-scale intelligence quotient (FSIQ) and memory quotient (MQ) of these patients were significantly improved 6 months postoperatively compared with preoperatively. The severity of alcohol dependence scale and a scale measuring alcohol craving in these patients were significantly decreased. There were also significant changes over time in the Minnesota multiphasic personality inventory (MMPI) profile, suggesting a decrease in depression, irritability, and psychopathy. Ablating specified targets (NAC) using stereotactic surgery is a safe method to alleviate alcohol craving, reduce relapse rates and improve quality-of-life in patients with psychological dependence on alcohol. [Copyright &y& Elsevier]

Abstract: Background: We investigated the safety of treatment of symptomatic intracranial atherosclerotic stenoses with the Gateway-Wingspan system and its initial effect on prevention of ischemic events. Methods: Twenty-seven cases of symptomatic intracranial atherosclerotic stenoses were treated with angioplasty with a Wingspan stent. Location of stenoses, extent of stenoses before and after angioplasty, success rate of treatment, occurrence of procedural complications, and changes in recurrence of symptoms of ischemic events 30 days after treatment were recorded. Results: Twenty-nine angioplasties with the Wingspan system were successfully carried out in 29 stenoses in 27 patients. Of 29 stenoses, 17 were in the posterior circulation, and 12, in the anterior circulation. The degree of stenoses was reduced from baseline 71.8% (56%-87.8%) to 24.9% (0%-45%) after stenting. Complications were seen in four patients (14.8%), 3 of which were lesion-related infarction of a perforated artery, and 1 was a non-lesion-related infarction. Two complications led to transient neurologic dysfunction, one led to defect of the visual field, and one led to hemiplegia. The prevalence of morbidity and serious morbidity were 7.4% and 3.7%, respectively, and no death occurred. No new ischemic events happened during 30 days after stenting. Conclusion: Angioplasty with the Wingspan system to treat symptomatic intracranial atherosclerotic stenoses appears to be safe. Its initial effect on prevention of ischemic events is acceptable. [Copyright &y& Elsevier]

Abstract: Astragalus membranaceus is widely used to treat stroke and chronic debilitating diseases in China, but the mechanism has not been fully demonstrated to data. In the present study, we, using astragaloside IV, a purified extract from astragalus membranaceus, to a focal cerebral ischemia/reperfusion rat model, aimed to investigate the effect of astragaloside IV on the permeability of the blood-brain barrier since disruption of blood-brain barrier induced by ischemia/reperfusion leads to serious brain injuries. We found that astragaloside IV (10, 20 mg/kg) significantly attenuated the permeability of blood-brain barrier in comparison with vehicle group after ischemia/reperfusion assessed via Evans blue leakage (P <0.05). This was further confirmed by examination of blood-brain barrier permeability under the electron microscope, using lanthanum as a tracer of blood vessel permeability. Lanthanum was usually found within the blood vessel in sham group, rather than in perivascular tissues as shown in vehicle group. In drug groups, lanthanum stain was mainly restricted within the cerebral capillary, indicating the potential protective effect of astragaloside IV on the integrity of blood-brain barrier in ischemia/reperfusion rats. Furthermore, we found that expression of occludin and zonae occludens-1 (ZO-1), the tight junction proteins, was decreased in endothelial cells in vehicle group, which, however, could be reversed by astragaloside IV administration. We propose that regulation of tight junctional proteins in the endothelial cells may be one mechanism astragaloside IV-mediated in attribution to blood-brain barrier protection in the ischemia/reperfusion rats. [Copyright &y& Elsevier]

Abstract: Abnormalities in the signal transducer and activator of transcription 5 (STAT5) signaling are involved in the oncogenesis of several cancers. However, previous studies have not elucidated clear and distinct roles for each STAT5 gene in cancers. To investigate the role of STAT5a, -5b isoforms in human glioblastoma multiforme (GBM) progression, we depleted each STAT5 isoforms with siRNA. Our results demonstrate that STAT5b is involved in GBM cell growth, cell cycle progression, invasion and migration through regulation of gene expression, such as Bcl-2, p21waf1/cip1, p27kip1, FAK and VEGF. Moreover, immunohistochemical staining reveals that cytoplasm staining of STAT5b is markedly increased in GBM (57.1%) compared with that in normal cortex (22.2%) and diffuse astrocytoma (27.3%), suggesting that STAT5b could have important implications in astrocytoma biology. Therefore, our findings illustrate the biological significance of STAT5b in GBM progression, and provide novel evidence that STAT5b may serve as a therapeutic target in the prevention of human glioblastoma multiforme. [Copyright &y& Elsevier]

It is well known that the nucleus accumbens plays an important role in drug reinforcing effect and relapse. However, the cellular neuroadaptations that take place in accumbens neurons after repeated drug exposure are still not well understood, especially for opioids. Here, we examined how nucleus accumbens neuronal excitability becomes affected in rats exposed to morphine using whole-cell patch-clamp recordings. Medium spiny neurons recorded from brain slices of repeated morphine treated rats exhibited a significant decrease in the intrinsic excitability after 3-4 days withdrawal, compared to that of neurons from saline treated animals, which was indicated by the increase of current to evoke the first spike and the decrease of spike number induced by depolarizing current steps in the morphine group. Moreover, the excitability decrease was accompanied by related membrane property changes, such as resting membrane potential hyperpolarization, input resistance, and membrane time constant decrease, inward rectification increase, and action potential duration decrease. Taken together, repeated morphine exposure and short-term withdrawal may reduce nucleus accumbens activity and output by modulating intrinsic membrane properties of its output neurons, which could be an important neuroadaptation process that mediates morphine addictive effect. Synapse 62:775-782, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: The clinic treatment of epilepsy with epileptic foci overlapped with eloquent cortex is not satisfactory. In this study we investigated the direct effects of low- and high-frequency electric cortical stimulation (ECS) on ferric chloride-induced seizures in the experimental rats. Results showed that spontaneous seizures were observed in all rats during the EEG recording after the intracortical injection of ferric chloride solution into left sensorimotor cortex. One-hertz or 100-Hz ECS with 0.3ms duration and 0.1mA amplitude square pulses in 1h on the cortical lesioned area significantly decreased the number of seizures compared with that of the non-stimulation control group. The mean duration time of seizures in 1-Hz or 100-Hz groups was apparently shorter than that in the control group. In brief, this study showed that both low- and high-frequency ECS suppressed the seizures induced by ferric chloride in rats, indicating their potential treatment effects on epilepsy in clinic. [Copyright &y& Elsevier]

Abstract: Lanthanum is one of rare earth cations with extremely active chemical property and has been reported to influence neuronal transmitter systems. To date, little attention has been directed towards the sacral dorsal commissural nucleus (SDCN), which serves as a relay of sensory information from the pelvic viscera in the spinal cord. Therefore, the effect of lanthanum on the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and glycine (Gly) responses in neurons acutely dissociated from the rat SDCN was investigated using the nystatin-perforated patch-recording configuration under voltage-clamp conditions. At a holding potential of −40 mV, La3+ reversibly potentiated GABA (3 μM)-activated currents (I GABA) in a concentration-dependent manner over the concentration range of 10 μM to 30 mM, with the EC50 value of 67.3±16.4 μM. Similarly, La3+ reversibly potentiated glycine (10 μM)-activated currents (I Gly) in a concentration-dependent manner over the concentration range of 1 μM to 1 mM, with the EC50 value of 52.3±10.9 μM. The effects of La3+ on I GABA and I Gly were voltage-independent. Moreover, both of the potentiations were not use-dependent and were overcome by increasing the concentration of agonist. Our results indicate that La3+ potentiates the inhibitory amino acid receptors-mediated responses in SDCN, which may reduce the transmission of the pelvic visceral information. The information provided by this work may help to elucidate the mechanisms and effects of lanthanum on brain functions. [Copyright &y& Elsevier]

Abstract: Background: Current evidence suggests that a majority of the inherited risks play a major role in glioma susceptibility, and glioma is due to the co-inheritance of multiple low-risk variants. These variants can be identified through association studies including such as genome-wide association studies (GWAS), which has led the glioma epidemiology researchers to focus on identifying potential disease-causing factors. Methods: We evaluated and validated 10 tag single nucleotide polymorphisms (tSNPs) in seven genes associated with glioma susceptibility in a Han Chinese population, including 301 glioma cases and 302 controls, using a multiplexed single nucleotide polymorphism (SNP) MassEXTEND assay. We ascertained the genotypic frequencies for each tSNP in control subjects were within Hardy–Weinberg equilibrium (HWE) using an exact test, and then compared the genotype and allele frequencies of glioma patients and control subjects using the χ2 test. We then applied three genetic models (dominant, recessive, and additive) using PLINK software to assess the association of each tSNP with glioma risk. Results: We identified two tSNPs to be associated with glioma susceptibility (rs1695, GSTP1, P =0.019; rs2853676, TERT, P =0.039), which we confirmed using dominant and additive model analyses. The genotype &ldquo;GA&rdquo; for rs1695 was recognized to be a protective genotype for glioma (OR, 0.67; 95% CI, 0.47–0.96; P =0.027), while the genotype &ldquo;AG&rdquo; for rs2853676 was shown to be a risk genotype for glioma (OR, 1.50; 95% CI, 1.05–2.15; P =0.025). Conclusion: Our results, and those from previous studies, suggest potential genetic contributes for GSTP1 and TERT in glioma development. [Copyright &y& Elsevier]

Background Symptomatic cavernous malformations involving the brainstem are difficult to access by conventional approaches, which often require dramatic brain retraction to gain adequate operative corridor. Here, we present a successful endoscopic endonasal transclival approach for resection of a hemorrhagic, symptomatic mesencephalic cavernous malformation. Case Description A 20-year-old woman presented with acute onset of headache, nausea, and vomiting. Computed tomography scan revealed a ventral midbrain hemorrhage. On day 3 of admission, the patient developed left-sided hemiparesis, restriction of medial and lateral left-eye movements, and loss of left pupillary light reflex. Subsequent magnetic resonance imaging demonstrated an increase of the midbrain lesion to 1.2 cm × 1.7 cm. Diffusion tensor imaging showed compression and lateral displacement of the right corticospinal tract near the thalamus and cerebral peduncle. Given the patient's clinical presentation and the findings on imaging, we suspected a mesencephalic cavernous malformation. Conclusions The patient underwent an endoscopic endonasal transclival resection of a ventral midline mesencephalon cavernous malformation. A dark red lesion was directly visualized under the endoscope. After a small cortiectomy, the pial and perforator vessels were dissected, and dark-brown blood was drained from the cavernoma cavity. Using a biopsy forceps and with careful attention to the cavernoma borders, the lesion was removed and hemostasis was achieved. Pathologic examination confirmed cavernous malformation. One week after the operation, magnetic resonance imaging demonstrated total resection of the lesion. A 3-month follow-up revealed improved neurologic symptoms with minimal surgical morbidity. [ABSTRACT FROM AUTHOR]

Background: Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery because of psychological dependence. Multiple studies identify a central role of the nucleus accumbens (NAc) in addiction; several studies note decreased addictive behavior after interventions in this area. Methods: Based on animal experiments, our institute started the clinical trial for the treatment of drug addicts’ psychological dependence by making lesions in the bilateral NAc with stereotactic surgery from July 2000. Results: The short-term outcomes were encouraging and triggered rapid application of this treatment in China from 2003 to 2004. However, lack of long-term outcomes and controversy eventually led to halting the surgery for addiction by the Ministry of Health of China in November 2004 and a nationwide survey about it later. Our institute had performed this surgery in 272 patients with severe heroin addiction. The follow-up study showed that the 5-year nonrelapse rate was 58% and the quality of life was significantly improved. Patients had several kinds of side effects, but the incidence rate was relatively low. The patients gradually recovered more than 5 years after the surgery. The side effects did not severely influence an individual’s life or work. Nationwide surgery showed that the nonrelapse rate was 50% in the sample of 150 cases, from 1167 patients overall who underwent stereotactic surgery in China. Conclusions: Although sometimes accompanied by neuropsychological adverse events, stereotactic ablation of NAc may effectively treat opiate addiction. Lesion location has a significant impact on treatment efficacy and requires further study. Because ablation is irreversible, the NAc surgery for addiction should be performed with cautiousness, and deep brain stimulation (DBS) is an ideal alternative. [Copyright &y& Elsevier]