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Abstract The objective of this study was to examine whether ultrasound can examine the development of cerebral vascular structure and cerebral blood flow in Sprague–Dawley (SD) rats by ultrasound in a noninvasive manner, which provides a reference for ultrasound research of SD rats. Thirty‐nine SD rats (7–16 days old) were divided into seven groups according to age, and the number of SD rats in each group was, respectively, 7, 17, 1, 3, 2, 8, and 1. Ultrasound was used to detect cerebral blood vessels, cerebrovascular flow velocity, and heart rate in SD rats in the sagittal and coronal positions, and images were obtained in B‐mode ultrasound. The cerebral vascular structure of 39 SD rats (7–16 days) was dynamically observed under B‐ultrasound. We found that the cerebral vascular structure of the rats aged 7–10 days was clear and detectable. Rats aged 11–16 days of cerebral vascular structures became thinner and undetectable. Quantitative analysis of cerebrovascular flow rate and heart rate in rats found that there was no significant difference in cerebrovascular blood flow rate and heart rate between 7 and 8 days. Ultrasound can also be used in rat animal studies, that is, the cerebral blood flow in rats of different ages can be monitored in real‐time by ultrasound in a noninvasive way.

Abstract The objective of the study is to investigate the brain development and atrophy of Diannan small‐ear pigs in different ages using magnetic resonance imaging (MRI). A total of 12 Diannan small‐ear pigs were included and divided into the young group, adult group, and middle‐and‐old age (M&O) group according to their age. The brain structure of pigs was scanned using MRI, and the brain data obtained were statistically analyzed by signal conversion and image reconstruction. Compared with the young group, the signals of most brain structures in the adult group and M&O group were significantly decreased (p

Abstract Neonatal hypoxic‐ischemic encephalopathy (NHIE) causes devastating cerebral damage and neurological deficits that seldom have effective therapies. This study aimed to explore the mechanisms underlying the therapeutic efficacy of Scutellarin in NHIE. NHIE models were successfully established. Zea‐longa score and triphenyte‐trazoliumchloride (TTC) staining demonstrated that hypoxia and ischemia (HI) insult induced prominent neurological dysfunctions and brain infarction. Protein microarray was applied to detect the differentially expressed genes in the cortex, hippocampus, and lung tissues of HI rats, which revealed the downregulation of vascular endothelial growth factor (VEGF) in these tissues. Additionally, double immunostaining uncovered VEGF expression was localized in the neurons. Besides, VEGF was decreasingly expressed in oxygen‐glucose deprivation (OGD) neurons, which was intriguingly reversed by Scutellarin treatment. Moreover, VEGF silencing increased OGD‐induced neuronal apoptosis and attenuated neurite outgrowth, which was enhanced by Scutellarin administration. GeneMANIA predicted a close correlation of VEGF with caspase 3, caspase 7, and interleukin (IL)‐1β, and qRT‐PCR revealed that Scutellarin treatment depressed the expression levels of them elevated in OGD neurons, but the Scutellarin‐depressed levels of these factors were prominently increased after VEGF silencing. Our findings suggested that Scutellarin exerted neuroprotective effects in NHIE potentially through mediating VEGF‐targeted inactivation of caspase 3, caspase 7, and IL‐1β.

ObjectiveThis study aimed to investigate the feasibility of Transcranial Doppler Ultrasonography (TCD) in evaluating neonatal hypoxic-ischemic encephalopathy (NHIE) modeling through monitoring the alteration of cerebrovascular flow in neonatal hypoxic-ischemic (HI) rats.MethodsPostnatal 7-day-old Sprague Dawley (SD) rats were divided into the control group, HI group, and hypoxia (H) group. TCD was applied to assess the changes of cerebral blood vessels, cerebrovascular flow velocity, and heart rate (HR) in sagittal and coronal sections at 1, 2, 3, and 7 days after the operation. For accuracy, cerebral infarct of rats was examined by 2,3,5-Triphenyl tetrazolium chloride (TTC) staining and Nissl staining to simultaneously verify the establishment of NHIE modeling.ResultsCoronal and sagittal TCD scans revealed obvious alteration of cerebrovascular flow in main cerebral vessels. Obvious cerebrovascular back-flow was observed in anterior cerebral artery (ACA), basilar artery (BA), middle cerebral artery (MCA) of HI rats, along with accelerated cerebrovascular flows in the left internal carotid artery (ICA-L) and BA, decreased flows in right internal carotid artery (ICA-R) relative to those in the H and control groups. The alterations of cerebral blood flows in neonatal HI rats indicated successful ligation of right common carotid artery. Besides, TTC staining further validated the cerebral infarct was indeed caused due to ligation-induced insufficient blood supply. Damage to nervous tissues was also revealed by Nissl staining.ConclusionCerebral blood flow assessment by TCD in neonatal HI rats contributed to cerebrovascular abnormalities observed in a real-time and non-invasive way. The present study elicits the potentials to utilize TCD as an effective means for monitoring the progression of injury as well as NHIE modeling. The abnormal appearance of cerebral blood flow is also beneficial to the early warning and effective detection in clinical practice.

Abstract Glioma is one of the most common primary brain tumors, and mortality due to this disease is second only to cardiovascular and cerebrovascular diseases. In traditional surgery, it is difficult to eradicate glioma; often recurrence increases its malignant degree, leading to a large number of patients killed by this disease. It is one of the most important subjects to study its pathogenesis and explore effective treatment methods. Research on glioma mechanisms mainly focuses on the effect of DNA methylation in epigenetics. Although there are many studies on protein phosphorylation, there is no overall regulatory mechanism. Protein phosphorylation regulates a variety of cell functions, such as cell growth, division and differentiation, and apoptosis. As a consequence, protein phosphorylation plays a leading part in various activities of glioma, and can also be used as a target to regulate the development of glioma. This review is aimed at studying the effect of protein phosphorylation on glioma, understanding the pathological mechanism, and an in‐depth analysis of it. The following is a discussion on glioma growth, migration and invasion, resistance and death in phosphorylation, and the possibility of treating glioma by phosphorylation.

Abstract Alzheimer's disease (AD) is a degenerative brain disease with complex clinical manifestations and pathogeneses such as abnormal deposition of beta‐amyloid protein and inflammation caused by the excessive activation of microglia. CXC motif chemokine receptor type 4 (CXCR4) is a type of G protein‐coupled receptor that binds to CXC motif ligand 12 (CXCL12) to activate downstream signaling pathways, such as the Janus kinase/signal transducer and activator of transcription and the renin–angiotensin system (Ras)/RAF proto‐oncogene serine (Raf)/mitogen‐activated protein kinase/extracellular‐regulated protein kinase; most of these signaling pathways are involved in inflammatory responses. CXCR4 is highly expressed in the microglia and astrocytes; this might be one of the important causes of inflammation caused by microglia and astrocytes. In this review, we summarize the mechanism and therapeutics of AD, the structures of CXCR4 and the CXCL12 ligand, and the mechanisms of CXCR4/CXCL12 that are involved in the occurrence and development of AD. The possible treatment of AD through microglia and astrocytes is also discussed, with the aim of providing a new method for the treatment of AD.

Abstract This study aimed to explore the possible target and mechanism of the wheel treadmill (WTM) test for motor function recovery of spinal cord injury (SCI). Rats were divided into sham, control and WTM groups to establish an SCI mode. Rats in the WTM group were trained on the WTM test, and Basso–Beattie–Bresnahan (BBB) scores were determined. The samples were collected, and mRNA sequencing was conducted to determine the changes in gene expression. The coexpressed genes were screened to construct a protein–protein interaction (PPI), followed by the Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology function enrichment analysis, and the differentially expressed genes (DEGs) volcano map and hub gene expression heat map were constructed using R language. The BBB scores in the control and WTM groups increased with time, with the WTM group scoring higher than the control group. The results of rat spinal cord tissue sequencing showed that a total of 1679 DEGs were screened in the sham and control groups; 928 DEGs and 731 overlapping genes were screened in the WTM and control groups. The key genes were identified by PPI analysis. One hundred and thirty‐three genes were found to be overlapping by combined analysis of spinal cord sequencing data and BBB scores of rats at Week 7. The top 10 DEGs from high to low were Tyrobp, Rac2, Cd68, C1qb, Aif1, Cd74, Spi1, Fcer1g, RT1‐DA, and Ccl4. The terms with the highest enrichment scores were microglia‐mediated positive regulation of cytotoxicity and major histocompatibility complex class II protein complexes. Treatment with the WTM test promotes recovery of motor function after SCI in rats by modulating intercellular communication and immune function.

Background Hypoxic‐ischemic encephalopathy (HIE) could induce exacerbated changes and unpredictable effects in brain cells, and the mechanism remains unclear. Methods HIE model was established in neonatal rats, Zea‐Longa score and TTC staining were used to observe the neurobehavior and brain infarct volume in rats subjected to cerebral hypoxia‐ischemia (HI). Primary cortical neurons were then cultured in vitro to establish an oxygen and glucose deprivation model. To determine the role of synaptosomal‐associated protein‐25 (SNAP25) in HIE, PC12 cells were cultured and effective siRNA fragments were screened, and SNAP25 was transfected into primary neurons. Then, quantitative real‐time polymerase chain reaction was used to detect the mRNA expression level and immunofluorescence staining was used to observe the morphological changes of neurons before and after the injury. Finally, the abundance values of SNAP25 and its associated genes were filtered using the NCBI and GeneMANIA, respectively. Results HI leads to a decrease in neuronal number and an increase in SNAP25 expression. Whereas, the interference of SNAP25 caused marked decrease in neuronal number and the length of neurite. Moreover, the expression levels of CREB and SYP were significantly decreased after interference of SNAP25. Conclusion SNAP25 exhibited several neuroprotective effects to neuronal protection in neonatal cerebral HI by regulating CREB and SYP.

Objective To explore the role of Neurotropfin‐3 (NT‐3) in hypoxic‐ischemic encephalopathy (HIE) and determine its relative molecular mechanism. Methods The expression of NT‐3 was determined by qRT‐PCR in the cortex after HIE and immunofluorescence staining was used to detect the distribution of NT‐3. Then, the NT‐3 siRNA was used to validate the effect of NT‐3 for the neuroprotection by the measurement of cell apoptosis after oxygen‐glucose deprivation (OGD). Lastly, the molecular network mechanism was studied by NT‐3 interference experiment combined with bioinformatics technology. Results The expression of NT‐3 was significantly upregulated after HIE, and NT‐3 was co‐localized in the neurons of the cortex. Furthermore, the inhibition of NT‐3 increased neuronal apoptosis after OGD and elicited the down‐regulation of BDNF and NGF. Conclusion NT‐3 is a vital neurotrophic factor that can maintain neonatal survival in cortical neurons, and the underlying mechanism is associated with BDNF and NGF regulation.

Interleukin 10 (IL-10) is a synthetic inhibitor of human cytokines with immunomodulatory and anti-inflammatory effects. This study was designed to investigate the expression variation of IL-10 in the multiple sites including cortex, hippocampus, and lung tissues of neonatal hypoxic-ischemic (HI) rats and explore the crucial role of IL-10 in alleviating HI brain damage. In this study, neonatal Sprague-Dawley rats were subjected to the right common carotid artery ligation, followed by 2 h of hypoxia. The expression of IL-10 in the cortex, hippocampus, and lung tissues was measured with immunohistochemistry, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot (WB). Immunofluorescence double staining was performed to observe the localization of IL-10 in neurons and astrocytes. Moreover, not-targeting and targeting IL-10 siRNA lentivirus vectors were injected into the rats of the negative control (NC) and IL-10 group, respectively, and the mRNA levels of B-cell lymphoma 2 (Bcl-2) and endoplasmic reticulum protein 29 (ERp29) were detected by RT-qPCR following IL-10 silence. The results demonstrated that the IL-10 expression was markedly increased after HI and IL-10 were colocalized with neurons and astrocytes which were badly injured by HI insult. In addition, Bcl-2 and ERp29 were remarkably decreased following IL-10 mRNA interference compared with the NC group. Our findings revealed that IL-10 exerted its antiapoptotic and neuroprotective effects by regulating the expression of Bcl-2 and ERp29, indicating that IL-10 may be a promising molecule target for HIE treatment.

The properties of graphene oxide (GO)-based cement paste can be significantly affected by the state of GO dispersion. In this study, the effects of uniformly dispersed and re-agglomerated GO on the rheological, mechanical properties and microstructure of cement paste were systematically investigated. Two distinct dispersion states can be achieved by altering the mixing sequence: Polycarboxylate-ether (PCE) mixed with GO-cement or cement mixed with GO-PCE. The experimental results showed that the yield stress and plastic viscosity increased with the uniformly dispersed GO when compared to those of re-agglomerated GO cement paste. Moreover, the 3-day compressive and flexural strengths of uniformly dispersed GO paste were 8% and 27%, respectively, higher than those of re-agglomerated GO pastes. The results of X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy analyses demonstrated that uniformly dispersed GO more effectively promotes the formation of hydration products in hardened cement paste. Furthermore, a porosity analysis using mercury intrusion porosimetry revealed that the homogeneous dispersion of GO can better inhibit the formation of large-size pores and optimize the pore size distribution at 3 and 7 days than the re-agglomerated GO.