Effect of LncRNA MEG3 on blood-brain barrier in neonatal mice with hypoxic-ischemic brain injury by targeting miR-17-5p / 临床神经病学杂志

Objective To analyze the effect of LncRNA MEG3 on the blood-brain barrier in neonatal mice with hypoxic-ischemic brain injury(HIBD)by regulating miR-17-5p.Methods A total of 90 C57BL mice were randomly grouped into control group,model group,si-NC group,si-LncRNA MEG3 group,si-LncRNA MEG3+anti-miR-NC group and si-LncRNA MEG3+anti-miR-17-5p group,with 15 mice in each group.Except for the control group,the rest of the mice were constructed with HIBD model,and the Longa score was used to evaluate the nerve damage of mice.The ultrastructure of vascular endothelial cells around brain tissue was observed by electron microscope.The permeability of blood-brain barrier in mice was measured by EB method.The levels of LncRNA MEG3 and miR-17-5p in the brain tissue of mice in each group were determined by qRT-PCR.The levels of ZO-1 and Occludin protein in the brain tissue of mice were determined by Western blotting.Results Compared with control group,the vascular endothelium of mice in model group was unevenly thin and thick,and showed edema in many places.Compared with model group,the vascular endothelial cells in the si-LncRNA MEG3 group were gradually tightly connected,the thickness was more uniform,and the edema was reduced.Compared with the si-LncRNA MEG3 group,vascular endothelial cell damage was intensified in the si-LncRNA MEG3+anti-miR-17-5p group.Compared with those in the control group,the neurological deficit score,brain water content,EB content,and LncRNA MEG 3 level in the model group were significantly increased,miR-1 7-5 p level,ZO-1 and Occludin expression were significantly decreased(all P＜0.05).Compared with those in model group,there were no significant differences in neural function deficit score,brain water content,EB content,lncRNA MEG3 level,miR-17-5p level,ZO-1 and Occludin expression in si-NC group(all P＞0.05);the neurological deficit score,brain water content,EB content and LncRNA MEG3 level in si-LncRNA MEG3 group were significantly decreased,miR-17-5p level,ZO-1,and Occludin expression were significantly increased(all P＜0.05).Compared with those in si-LncRNA MEG3 group,there were no significant differences in neural function deficit score,brain water content,EB content,LncRNA MEG3 level,miR-17-5p level,ZO-1 and Occludin expression in si-LncRNA MEG3+anti-miR-NC group(all P＞0.05);the neurological deficit score,brain water content and EB content in si-LncRNA MEG3+anti-miR-17-5p group were significantly increased,miR-17-5p level,ZO-1 and Occludin expression were significantly decreased(all P＜0.05).Conclusion LncRNA MEG3 silencing may reduce the permeability of the blood-brain barrier in neonatal mice with HIBD by up-regulating miR-17-5p,maintaining the protective effect of the blood-brain barrier on the brain,and protecting brain tissue.

Effects of Shujin Jiannao Prescription on cell apoptosis in rats with hypoxic-ischemic brain injury / 中国组织工程研究

BACKGROUND:Perinatal hypoxic-ischemic brain injury is one of the most common causes of cerebral palsy.Shujin Jiannao Prescription is an experienced formula for treating cerebral palsy and improving blood supply to the brain developed by the Dongzhimen Hospital,Beijing University of Chinese Medicine. OBJECTIVE:To explore the possible mechanism of Shujin Jiannao Prescription in treating hypoxic-ischemic cerebral palsy. METHODS:Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into six groups.There were 12 rats in each of the control and model groups as well as 10 animals in each of the minocycline group,and the low-,medium-,and high-dose groups of Shujin Jiannao Prescription.The neonatal rat ischemic-hypoxic cerebral palsy model was established in all groups except for the control group.After successful modeling,rats in each drug group were respectively gavaged with minocycline and Shujin Jiannao Prescription at a dose of 4,8,and 16 g/kg per day for 1 week.Body mass of rats was measured and behavioral changes were detected before and after drug administration.Hematoxylin-eosin staining was used to observe the histomorphology of hippocampal CA1 region of rat brain tissue,and immunohistochemistry and western blot were used to detect the expression levels of Bcl-2,Bax,and Caspase-3 in the brain tissue of rats. RESULTS AND CONCLUSION:Compared with the model group,medium-and high-dose Shujin Jiannao Prescription significantly increased the body mass of rats(P<0.05).Compared with the model group,minocycline effectively prolonged the suspension time of ischemic-hypoxic cerebral palsy rats(P<0.05),while medium-and high-dose Shujin Jiannao Prescription significantly prolonged the suspension time,shortened the inclined plane test time,and increased the Longa score of rats(P<0.05).The pathological results showed that after drug intervention,only a small number of neuronal cells in the brain tissue of rats were necrotic,the cells were more neatly arranged,the cell structure was more complete,and only part of the cell nuclei became smaller.Compared with the model group,minocycline and medium-and high-dose Shujin Jiannao Prescription reduced the expression of Bax Caspase-3(P<0.05),medium-and high-dose Shujin Jiannao Prescription increased the expression of Bcl-2(P<0.05),and Bcl-2/Bax protein expression was increased in minocycline and three Shujin Jiannao Prescription groups(P<0.05).In addition,the protein expression was increased in a dose-dependent manner after intervention with Shujin Jiannao Prescription,and there was no significant difference between the minocycline and three Shujin Jiannao Prescription groups(P>0.05).To conclude,the mechanism by which Shujin Jiannao Prescription treats ischemic-hypoxic cerebral palsy in rats may be to enhance the expression of anti-apoptotic protein Bcl-2,inhibit the expression of pro-apoptotic protein Bax,and reduce the expression of Caspase-3,ultimately inhibiting the apoptosis of hippocampal neuronal cells in rats with cerebral palsy.Within a certain range,the higher dose of Shujin Jiannao Prescription indicates the better therapeutic effect,and the high-dose Shujin Jiannao Prescription is as effective as minocycline.

The changing levels of GluR2 phosphorylation in oligodendrocyte precursor cells in mice model of ischaemic hypoxia / 神经解剖学杂志

Objective:To investigate the expression of phosphorylated glutamate receptor 2[p-GluR2(S880)]in oligodendrocyte precursor cells(OPCs)of mice model of hypoxic ischemic brain injury(HIBI).Methods:The HIBI model of C57BL/6 neonatal mice was established by right common carotid artery ligation and hypoxia for 90 min.The anxiety-like behavior of the mice was evaluated by elevated plus maze(EPM)and open field test(OFT).The expres-sion of p-GluR2(S880),oligodendrocyte marker 4(O4)and myelin basic protein(MBP)in brain tissue of HIBI model mice was detected by immunofluorescence staining.What's more,the expression levels of p-GluR2(S880)and MBP were detected by Western Blot.Results:Compared with sham operation group,there were significant anxiety-like behaviors 90 days after HIBI operation(P＜0.05).The expression of MBP protein decreased significantly in 14 and 28 days after HIBI operation.The expression of p-GluR2(S880)protein was up-regulated at all time points after HIBI op-eration(P＜0.05),and the number of O4 and p-GluR2(S880)double positive cells in brain tissue of HIBI group was significantly increased(P＜0.05).Conclusion:The up-regulation of p-GluR2(S880)expression in OPCs may lead to myelination disorder in HIBI model mice.

Effect and mechanism of 6-gingerol on neonatal hypoxic-ischemic encephalopathy and cognitive behavior in neonatal mice / 解剖学报

[Abstract] Objective To investigate the effect of 6-gingerol treatment on cognitive behavior after hypoxic-ischemic brain injury (HIE) in neonatal mice, and to explore the protective mechanism of 6-gingerol on HIE brain injury in neonatal mice by observing the effects on neuronal survival and neural stem cell proliferation. Methods The right common carotid artery was ligated in Kunming mice (78) on the 7th day after birth and HIE model was established after 90 minutes of hypoxic treatment. 6-gingerol was injected intraperitoneally. The cognitive behavior was detected by Morris water maze test; 2,3,5-triphenyl tetrazolium chloride (TTC) staining was used to observe the changes of brain injury; The changes of synaptic structure and number were obseved by transmission electron microscopy; HE staining, Nissl staining and dihydroethidium(DHE) staining were used to observe the pathomorphological changes of hippocampus in each group; The proliferation of neural stem cells and the expression of related transcription factors were detected by immunofluorescence and Real-time PCR; The changes of Akt signal pathway were detected by Western blotting. Results 6-gingerol treatment could improve the long-term learning and memory ability, reduce the brain injury and brain edema of neonatal mice after HIE, and improve synaptic plasticity of mice after HIE. In the 6-gingerol treatment group, the disorder of hippocampal cells in the diseased side of HIE was improved, the number of necrotic cells decreased, the proliferation ability of hippocampal neural stem cells and the expression levels of nestin and sex determining region box transcription factor 2 (Sox2) related transcription factors increased significantly, and the level of phosphorylated Akt (p-Akt) increased. Conclusion It is found that 6-gingerol can improve the learning and memory ability of HIE mice in adulthood and reduce brain tissue injury after HIE. 6-gingerol may play a role in inhibiting the production of reactive oxygen species(ROS), reducing neuronal injury and upregulating the expression of Akt signal pathway, promoting the proliferation of hippocampal neural stem cells, so as to provide potential drugs for the treatment of neonatal HIE.

Preparation and evaluation of experimental animal models of ischemic brain injury / 中国药理学通报

Aim Ischemic brain injury ( IBI) is one of the main causes of death and disability worldwide.Faced with this serious disease, human beings still laek effective treatment methods.With the advancement of science and the improvement of medi¬cal standards, the basic and clinieal research of cerebrovaseular diseases continues to develop to a higher and more in-depth lev¬el.Due to the limitations of clinical researeh, animal models of eerebral ischemia have beeome an indispensable tool for studying the mechanism of cerebrovascular disease damage and prevention and treatment measures.It is necessary to construct scientific, standard and standardized experimental methods and proee- dures..Methods This artiele combines our laboratory s long-tenn praetieal experienee in preparing animal models of cerebral is¬chemia.comprehensive literature data, comparison and evalua¬tion of the characteristics of commonly used animal models.Re¬sults Standardized preparation methods and discusses the com¬mon criteria for preparing experimental animal models of cerebral Ischemia, which is the occurrence of cerebral ischemia injury.Conclusions 'Hie researeh of mechanism and the researeh and de¬velopment of prevention and treatment drugs provide reliable ex¬perimental animal models.

Preparation of drug loading system of black phosphorus nanosheets and its anti-ischemic brain injury / 药学学报

In this study, black phosphorus nanosheets (BP) were prepared by the ordinary liquid phase method, and resveratrol was loaded on the BP after being modified by polyethylene glycol. The brain targeting of BP was investigated by fluorescent protein labeling, and the effects of black phosphorus on cerebral ischemia/reperfusion injury were studied by 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurobehavioral evaluation, and brain edema. Protein immunoblotting analysis was used to explore the molecular mechanism of the BP drug delivery system on ischemic brain injury. Hemolysis test and hematoxylin-eosin (H&E) staining were used to evaluate its biocompatibility. The results showed that BP had excellent drug loading capacity, uniform drug loading system structure and particle size, stable drug release curve, and excellent photothermal effect. Through the analysis and comparison of fluorescence intensity, it was found that BP can increase the permeability of blood-brain barrier (BBB) under the condition of near-infrared light assisted irradiation, and make drugs more pass through the BBB. In addition, the black phosphorus nano tablet drug delivery system can significantly improve the neurobehavioral disorder of mice after modeling, and the cerebral infarction area and brain edema degree are significantly decreased. Western blot experiments showed that the drug delivery system could play an anti-ischemic brain injury role by activating the expression of antioxidant signaling pathway proteins nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). The hemolysis test and H&E test results of the BP drug carrier system showed that it had no obvious toxicity and high safety. In conclusion, the BP prepared in this study had high drug loading, good photothermal performance, and high safety. Under the near-infrared condition, they also have certain brain targeting ability, which can improve the therapeutic effect of drugs in the brain. Animal welfare and experimental procedures were following the regulations of the Animal Ethics Committee of the First Affiliated Hospital of Shihezi University.

Expression of costimulatory molecule OX40 in peripheral regulatory T cells and its clinical significance in patients with acute cerebral infarction / 中华神经医学杂志

Objective:To investigate the expression of costimulatory molecule OX40 in peripheral CD4 +CD25 +CD127 low regulatory T (Treg) cells and its clinical significance in patients with acute cerebral infarction (ACI). Methods:Seventy-five patients with first-onset ACI, admitted to our hospital from April 2019 to December 2019, and 36 age- and gender-matched volunteers (control group) were selected in this study. OX40 expression on CD4 +CD25 +CD127 low Treg cells in peripheral blood samples in the two groups were analyzed by immunofluorescent labeling and flow cytometry. Correlations of OX40 +Treg cell percentage with National Institute of Health stroke scale (NIHSS) scores, ischemic penumbra volume, core infarct volume, and infarct volume in the patient group were analyzed. The changes of OX40 +Treg cell percentage in the patient group before and after endovascular treatment or intravenous thrombolysis were compared. Results:As compared with that in the control group, the Treg cell percentage in peripheral blood samples of the patient group was significantly decreased, while OX40 +Treg cell percentage was significantly increased ( P<0.05). OX40 +Treg cell percentage was positively correlated with NIHSS scores in ACI patients ( r s=0.271, P=0.018). Meanwhile, OX40 +Treg percentage was significantly correlated with ischemic penumbra volume, core infarct volume, and infarct volume in the patient group ( r s=0.435, P=0.000; r s=0.343, P=0.003; r s=0.245, P=0.034). OX40 +Treg cell percentage in ACI patients 7 d after endovascular treatment was significantly decreased as compared with that before treatment ( P<0.05); OX40 +Treg percentage in ACI patients 3 and 7 d after intravenous thrombolysis was significantly decreased as compared with that before treatment ( P<0.05). Conclusion:OX40 is abnormally expressed on peripheral Treg cells in ACI patients, and is closely correlated with neurological deficits, imaging features and reperfusion therapy.

The expression of MFGE8 in ischemic brain injury and its regulation of macrophage polarization / 中风与神经疾病杂志

@#Objective　To investigate the expression of protein tyrosine kinase 2 (MFGE8) in patients with ischemic brain injury (IBI) and its regulation on macrophage polarization.Methods　ELISA was used to detect the expression of MFGE8 protein in peripheral blood of patients with ischemic stroke and middle cerebral artery occlusion (MCAO) rat models;IF was used to detect the localization and expression of MFGE8 in brain;BV-2 microglia was treated with the culture supernatant of N2a neuronal cells (Mfge8CA) stably transformed with Mfge8.The polarization ratio of macrophages was detected by flow cytometry.Western blot detection Mfge8,αv/β 3-integrin,FAK,NF-κB.ERK1/2,JNK1/2,P38,PI3K,AKT,mTOR protein expression.Results　The relative content of MFGE8 in peripheral blood of IBI patients and MCAO model rats was significantly lower than that of the control group (Ctrl,P=0.0446,P=0.0259).MFGE8 was highly co-localized with neuron cell marker (NeuN);the proportion of M1 type (CD45+F4/80+iNOS+Arginase1-) macrophages in the brain tissue of MCAO model was significantly higher than that in the Ctrl (P=0.0004).The proportion of M2 type (CD45+F4/80+iNOS-Arginase1+) macrophages was significantly lower than that of the Ctrl (P<0.0001).The proportion of M1 macrophages of BV-2 microglia after supernatant of N2a (mfge8CA) treatment was significantly lower than that of Wild type (WT,P=0.0230).The proportion of M2 macrophages was significantly higher (P<0.0001).The protein expressions of α v/β3-integrin,FAK,p-P85,P85,p-AKT (Ser473),p-mTOR (Ser2481) and p-mTOR (Ser2488) in BV-2 microglia after supernatant of N2a (mfge8CA) treatment were significantly higher than those in WT group.The expression of p-P65 protein was significantly lower than that in WT group.Conclusion　MFGE8 is highly expressed in peripheral blood of patients with IBI.MFGE8 derived from neuronal cells may promote BV-2 microglia M2 macrophages polarization by activating PI3K/AKT/mTOR signals,and inhibit the polarization of M1 macrophages.

Study on neuroprotective mechanism of salidroside after ischemic stroke based on TGF-β1/Smad3 signaling pathway / 中草药

Objective: To investigate the neuroprotective mechanism of salidroside after ischemic stroke and its regulation mechanism in TGF-β1/Smad3 signaling pathway. Methods: A total of 48 SPF SD male rats aged 12-15 weeks were randomly divided into four groups (n = 12): Sham-operated group (sham group), model group, salidroside group (treatment group), and signaling pathway-enhanced intervention group (TGF-β1 group). In the model group, treatment group, and TGF-β1 group, a permanent focal cerebral ischemia rat model was established by suture method, and the sham group was not inserted with nylon thread. 48 h before the modeling operation, the treatment group and the TGF-β1 group were given drug intervention at a fixed time every morning: the treatment group was administered with 10 mg/kg salidroside ventricle, and the TGF-β1 group was treated with 20 mg/kg TGF-β1. The intraventricular injection was administered, and the sham group and the model group were given an equal volume of physiological saline. After 14 d of continuous administration, each group of rats was sacrificed by decapitation. TTC staining, Nissl staining, TUNEL staining, immunofluorescence, and Western blot were used to determine the infarct volume, the number of intact neurons, the cell apoptosis, the expression of Bax and Bcl-2 expression, the expression levels of Bax, Bcl-2, TGF-β1, and p-Smad3. The ultrastructural changes of brain tissue were observed by electron microscopy. Results: Compared with the sham group, the cerebral infarction volume of the model group was significantly increased, the number of intact neurons in the brain tissue was significantly reduced, the apoptosis rate of nerve cells was significantly increased, and the expression of Bax was significantly increased, the expression of Bax was significantly decreased. The expression of TGF-β1 and p-Smad3 was significantly increased, and the difference was statistically significant (P 0.05). Conclusion: Salidroside can activate the TGF-β1/Smad3 signaling pathway after ischemic stroke, thereby alleviating neurological damage and exerting protective effects on nerve cells.

Advances in the measures to reduce ischemic brain injury after carotid artery stenting / 中国脑血管病杂志

Ischemic brain injury after carotid artery stenting (CAS) is a predictor of cognitive decline and clinical events of cerebral ischemia. Nowadays, the methods to reduce the incidence of ischemic brain injury after CAS include choosing the eligible patients, controlling the risk factors, using the antiplatelet aggregation drugs and statins, combining neuroprotective drugs, or non-pharmaceutical therapies, and selecting the appropriate type of stents and embolic protection devices individually. The standardized training of the operator is also important for reducing procedure-related complications. However, ischemic brain injury after CAS is still a common phenomenon. Further study is needed to develop a safe, economical and effective treatment to reduce the prevalence of CAS complications.

Identification of active components in Longxue Tongluo Capsules against ischemic brain injury based on component-activity relationship / 中国中药杂志

Ten fractions(A-J) were prepared by separation of Longxue Tongluo Capsules(LTC) by using silica gel column chromatography and orthogonal experimental design,showing similar chemical profiles with different abundances of peaks.These ten samples were assessed with UHPLC-QE OrbitrapHRMS for 97 common peaks.For the pharmacological activity experiment,three kinds of in vitro cell models including lipopolysaccharide(LPS)-induced BV-2 microglial cells NO release model,oxygen-glucose deprivation/reoxygenation(OGD/R)-treated HUVEC vascular endothelial cells injury model,and OGD/R-treated PC-12 nerve cells injury model were employed to evaluated the bioactivity of each fraction.Based on the contribution of each identified component,grey relation analysis and partial least squares(PLS) analysis were performed to establish component-activity relationship of LTC,identify the potential active components.After that,validation of the potential active components in LTC was carried out by using the same models.The results indicated that 4 phenolic compounds including 7,4'-dihydroxyhomoisoflavanone,loureirin C,4,4'-dihydroxy-2,6-dimethoxydihydrochalcone,and homoisosocotrin-4'-ol,might be the active components for anti-neuroinflammation effect;five phenolic compounds such as 3,5,7,4'-tetrahydroxyhomoisoflavanone,loureirin D,7,4'-dihydroxyhomoisoflavane,and 5,7-dihydroxy-4'-methoxy-8-methyflavane,might have positive effects on the vascular endothelial injury;three phenolic compounds including 5,7,4'-trihydroxyflavanone,7,4'-dihydroxy-5-methoxyhomoisoflavane,and loureirin D,might be the active components in LTC against neuronal injury.

Effects of Resveratrol on Cognitive Function and SIRT 1/NF-κB Signaling Pathway in Neonatal Rats with Hypoxic-ischemic Brain Injury / 中国药房

OBJECTIVE： To study the effects of resveratrol （Res） on cognitive function and SIRT1/NF-κB signaling pathway in neonatal rats with hypoxic-ischemic brain injury. METHODS： SD neonatal rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， Res low-dose and high-dose groups （30， 60 mg/kg）， with 12 rats in each group. Except that sham operation group received sham operation， hypoxic-ischemic brain injury model was established by Rice method in other groups. After modeling， the rats were given relevant medicine intraperitoneally each day， for consecutive 6 weeks. Water maze test was used to analyze spatial learning and memory function of rats in each group. The escape latency after 1， 3 and 6 weeks of administration and the times of crossing platform after 6 weeks of administration were recorded. TTC staining was used to detect cerebral infraction area of rats after 6 weeks of medication. Western blot was used to detect the expression of Bcl-2， Bax， Caspase-3， SIRT1， SIRT1/NF-κB pathway related protein SIRT1 and p-NF-κB in hippocampal CA1 region. RESULTS： Compared with sham operation group， escape latency of rats was prolonged significantly in model group after 1， 3， 6 weeks of medication （P＜0.05）， the times of crossing platform was decreased significantly after 6 weeks of medication （P＜0.05）； the area of cerebral infarction was increased significantly （P＜0.05）； the protein expression of Bax， Caspase-3 and p-NF-κB in hippocampus CA1 region were increased significantly， while the protein expression of Bcl-2 and SIRT1 were decreased significantly （P＜0.05）. Compared with model group， the escape latency of Res low-dose and high-dose groups were shortened significantly after 1， 3， 6 weeks of medication （P＜0.05）， while the times of crossing platform was increased significantly after 6 weeks of medication （P＜0.05）； the area of cerebral infarction was decreased significantly （P＜0.05）， and the protein expression of Bax， Caspase-3 and p-NF-κB protein in hippocampal CA1 area were decreased significantly， while the protein expression of Bcl-2 and SIRT1 were increased significantly （P＜0.05）. The improvement of above indexes in high-dose group were significantly better than low-dose group （P＜0.05）. CONCLUSIONS： Res can improve cognitive dysfunction in neonatal rats with hypoxic-ischemic brain injury， which is related with SIRT1/NF-κB signaling pathway.

Effect of Obesity Induced by High-fat Diet on Ischemic Brain Injury in Mice / 中国康复理论与实践

@#Objective To investigate the effect of diet-induced obesity on ischemia brain injury in mice.Methods A total of 60 male C57/Bl6 mice were treated with high-fat (high-fat group, n=30) or normal diet (control group, n=30) for three months, and each group was further divided into sham group and model group, with 15 mice in each subgroup. The model group was established the middle cerebral artery occlusion model. The nerve injury was evaluated with Neurologic Severity Score (NSS), the infarct volume was evaluated by 2,3,5- chlorinated three phenyl tetrazolium chloride (TTC) staining, the expression of sirtuin (Sirt1), Wnt and apoptosis inducing factor (AIF) were detected with Western blotting seven days after modeling.Results Seven days after modeling, the NSS was higher in the high-fat group than in the control group (t=10.053, P<; 0.05), and no significant difference was found in the infarct volume between two groups (t=6.872, P>; 0.05). The expression of Sirt1 (t=8.462, P<; 0.05) and AIF (t=8.471, P<; 0.05) was higher, and the expression of Wnt (t=17.752, P<; 0.01) was lower in the high-fat group than in the control group.Conclusion Obesity could affect the recovery of mice with MCAO, which may related with impaired Wnt signaling.

Autophagy and neuronal diseases / 中华危重病急救医学

Autophagy is a dynamic process that allows recycling of long-lived proteins and damaged organelles into biosynthetic materials for maintaining the normal cellular homeostasis. Recently, accumulating evidence has indicated that autophagy played important roles in the pathogenesis of neuronal diseases. In this article, the research progress of autophagy in the pathogenesis and regulation mechanism of common nervous system diseases were reviewed to deepen the understanding of autophagy, and arouse researchers' attention on dynamic regulation of autophagy and alleviating autophagic flow injury.

Research progress concerning miRNAs regulating autophagy in ischemic brain injury / 中华神经医学杂志

miRNAs,as a class of endogenous small noncoding RNAs,have come to be a new treatment target for ischemic brain injury as many of them have been discovered to participate in multiple links of the injury.Autophagy,a catalysis process based on lysosomes,has become a current research hotspot because it has been found to participate in and regulate the pathological process of ischemic brain injury.As regulation of autophagy by miRNAs represents a new post-transcriptional regulatory mechanism,autophagy miRNAs after ischemic brain injury have attracted growing interest trom researchers worldwide.It is expected that the role of miRNAs in autophagy regulation can be clarified with the research progress and new therapeutic targets and directions can be found for the treatment of ischemic brain injury.This review gives a brief summary of the research progress conceming the role of miRNAs in regulating autophagy after ischemic brain injury,hoping the information may promote understanding of the important effects and potential therapeutic values of miRNAs-regulated autophagy in ischemic brain injury.

Circular RNA and ischemia brain damage related to circular RNA / 国际儿科学杂志

Circular RNAs (circRNAs) are a class of highly stable,long non-coding RNAs (lncRNAs),which shows greater conserved across species and highly specific in different tissue and development stage.There are numerous circRNAs in the central nervous system,which are not only closely related to development,differentiation and biological function of neuronal cells,also play a crucial role in nerve lesions and dysfunction after brain injury.Specific circular RNA could contribute to the regulation of gene expression by acting as miRNA sponges,involving in the protection against apoptosis in neurons and regeneration after brain injury.A comprehensive understanding of the specific circular RNA function and its underlying mechanism in the brain can provide a new strategy for the prevention,diagnosis,and treatment of brain injury at gene level.

Effects of ginkgobalide B on neurocyte apoptosis and the expression of protein kinase B after experimental hypoxic-ischemic brain injury / 中华物理医学与康复杂志

Objective To observe the effect of ginkgobalide B (GB) on neurocyte apoptosis and protein kinase B expression in neonatal rats after hypoxic-ischemic brain damage (HIBD).Methods Ninety seven-day-old Sprague-Dawley rats were randomly divided into a sham group,an HIBD group and a GB group,each of 30.HIBD was induced in the HIBD and GB groups using the classical Rice method,while the sham group was given a sham operation.GB (10 mg/kg) was injected intraperitoneally to the rats in the GB group at 0 h and 24 h after the modeling.Then 6 rats were killed 6 h,12 h,24 h and 48 h after the modeling,and the expression of caspase-3 mRNA was detected using a real-time PCR to find the time point of maximum effectiveness.Then to further explore the role of the PI3K-AKT pathway in the anti-apoptosis effect of ginkgolide B,a a GB+LY294002 group of 6 rats,which was injected with PI3K-AKT pathway inhibitor LY294002 (1.8 mg/kg) intraperitoneally at 30 min before the modeling and with GB(10 mg/kg) at 0 h and 24 h after the modeling,was added to the experiment.Hematoxylin-eosin staining,terminal-deoxynucleotidyl transferase-mediated nick end labeling and immunohistochemical staining were then used to observe any morphological changes in the cortex,to detect neuronal apoptosis and to quantify the expression of P-AKT protein.Results The expression of caspase-3 in the HI and GB groups began to increase 6 hours after the HIBD and reached a peak after 24 hours,followed by a gradual decline.The expression of caspase-3 in the GB group was significantly lower than in the HI group throughout,while that of both of those groups was significantly higher than in the sham group.Apoptosis-positive cells and the expression of caspase-3increased had significantly in the HI,GB and GB+LY294002 groups 24 hours after the HIBD compared with the sham group,while the expression of P-AKT protein had decreased significantly.Moreover,the apoptosis-positive cells and the expression of caspase-3 of the HI and GB+LY294002 groups were significantly high-er than those of the GB group,while their expression of P-AKT protein was significantly lower after 24 hours.Conclusion Ginkgobalide B can decrease neurocyte apoptosis caused by hypoxic-ischemic brain damage,especially at 24 h after the damage.The PI3K-AKT signaling pathway plays an important role in this effect.

Effect of Enriched Environment on Motor and Social Function after Ischemic Brain Injury in Mice / 中国康复理论与实践

Objective To explore the role of long-term enriched environment in promoting the recovery of motor and social function in mice after ischemic brain injury. Methods Sixteen adult male ICR mice underwent permanent middle cerebral artery occlusion (MCAO). The first day after operation, they were divided into enriched environment group (n=8) and standard condition group (n=8). The mice were tested with modified Neurological Severity Score (mNSS), rotarod test and smart cage 7, 14, 21, 28 days after modeling. Results The score of mNSS and the result of rotarod test improved more in the enriched environment group than in the standard condition group 28 days after MCAO (t>2.927, P2.480, P0.05) in the social behavior test; however, the occupancy time in the middle of smart cage was longer in the enriched environment group than in the standard condition group 14 to 28 days after MCAO (t>3.472, P<0.01), and the velocity of moving was higher 14 days after MCAO (P<0.05). Conclusion Enriched environment could promote the recovery of motor function, somehow of social function, in mice af-ter ischemic brain injury.

Dual effect of microglia on ischemic stroke: a review / 中国药理学与毒理学杂志

Ischemic brain injury is the main cause of high mortality,high disability and high recurrence rates in ischemic stroke.The activation and differentiation of microglia are associated with inflammatory responses of ischemic brain injury,playing an important role in the occurrence,development and outcome of ischemic stroke.In addition,there is no effective treatment for ischemic stroke.Thus,it is of clinical significance to investigate regulatory mechanisms of microglia for ischemic stroke treatment.This review introduces the dual effect of microglia on ischemic stroke and research progress in associated treatment for ischemic stroke,hoping to provide new ideas for investigating targeted intervention therapies.

Effects of ginkgobalide B on neurocyte apoptosis and the expression of protein kinase B after experimental hypoxic-ischemic brain injury / 中华物理医学与康复杂志

Objective To observe the effect of ginkgobalide B (GB) on neurocyte apoptosis and protein kinase B expression in neonatal rats after hypoxic-ischemic brain damage (HIBD).Methods Ninety seven-day-old Sprague-Dawley rats were randomly divided into a sham group,an HIBD group and a GB group,each of 30.HIBD was induced in the HIBD and GB groups using the classical Rice method,while the sham group was given a sham operation.GB (10 mg/kg) was injected intraperitoneally to the rats in the GB group at 0 h and 24 h after the modeling.Then 6 rats were killed 6 h,12 h,24 h and 48 h after the modeling,and the expression of caspase-3 mRNA was detected using a real-time PCR to find the time point of maximum effectiveness.Then to further explore the role of the PI3K-AKT pathway in the anti-apoptosis effect of ginkgolide B,a a GB+LY294002 group of 6 rats,which was injected with PI3K-AKT pathway inhibitor LY294002 (1.8 mg/kg) intraperitoneally at 30 min before the modeling and with GB(10 mg/kg) at 0 h and 24 h after the modeling,was added to the experiment.Hematoxylin-eosin staining,terminal-deoxynucleotidyl transferase-mediated nick end labeling and immunohistochemical staining were then used to observe any morphological changes in the cortex,to detect neuronal apoptosis and to quantify the expression of P-AKT protein.Results The expression of caspase-3 in the HI and GB groups began to increase 6 hours after the HIBD and reached a peak after 24 hours,followed by a gradual decline.The expression of caspase-3 in the GB group was significantly lower than in the HI group throughout,while that of both of those groups was significantly higher than in the sham group.Apoptosis-positive cells and the expression of caspase-3increased had significantly in the HI,GB and GB+LY294002 groups 24 hours after the HIBD compared with the sham group,while the expression of P-AKT protein had decreased significantly.Moreover,the apoptosis-positive cells and the expression of caspase-3 of the HI and GB+LY294002 groups were significantly high-er than those of the GB group,while their expression of P-AKT protein was significantly lower after 24 hours.Conclusion Ginkgobalide B can decrease neurocyte apoptosis caused by hypoxic-ischemic brain damage,especially at 24 h after the damage.The PI3K-AKT signaling pathway plays an important role in this effect.