Protective effect of Shenmajing formula on ischemic brain injury in mice / 药学实践杂志

Objective To observe the protective effect of Shenmajing formula on brain tissue of mice with cerebral ischemic injury and explore the possible mechanism. Methods Thirty SPF-grade C57 BL/6 male mice were randomly divided into model control group, Shenmajing group and nimodipine group, and the animal models of cerebral ischemic injury in mice were prepared by electrocoagulation. The protein expression level in endothelial progenitor cells were detected by Western blot. Results Compared with the model control group, the infarct volume of mice in the Shenmajing group was significantly reduced, and the migration, adhesion and tubule formation ability of endothelial progenitor cells were significantly improved, and the expression level of BDNF protein in endothelial progenitor cells was significantly increased. Conclusion The protective effect of Shenmajing granules on brain tissue of mice with cerebral ischemic injury could be closely related to the regulation of BDNF expression in endothelial progenitor cells and improvement of endothelial progenitor cell function of bone marrow origin.

Investigation on endoplasmic reticulum stress mech-anism of ischemic stroke based on network pharma-cology / 中国药理学与毒理学杂志

OBJECTIVE To investigate the mecha-nism of endoplasmic reticulum stress in cerebral isch-emic stroke from a theoretical perspective based on net-work pharmacology.METHODS GeneCards and OMIM databases were used to screen out the related targets of cerebral ischemic stroke and endoplasmic reticulum stress.And Venny2.1.0 was used to draw Venn's diagram to get the intersecting genes between cerebral ischemic stroke and endoplasmic reticulum stress.String data-base was used to get the protein-protein interaction(PPI)diagram and cytoscape was used for visualization analy-sis.The key genes were screened out by cytohubba plug-in,and enrichment analysis was performed.RESULTS Network pharmacology showed that there were 3744 cerebral ischemic stroke-related targets and 8675 endo-plasmic reticulum stress-related targets.After screening,41 common targets were got.There were 37 nodes,390 edges in the PPI network,namely,there were 37 interact-ing proteins and 390 interacting relationships.The key genes identified by cytohubba plug-in were IL-6,ALB,INS,TNF,AKT1,CASP3,MAPK3,TP53,SIRT1 and VEGF.The biological process involves reaction to oxida-tive stress,the regulation of neuron death,and negative regulation of cell differentiation,etc.;cellular components were related to the membrane raft,smooth endoplasmic reticulum,endoplasmic reticulum lumen and other com-ponents;molecular function aspects were related to sig-naling receptor activator activity,chaperone binding and protease binding.Enrichment analysis of pathway revealed that the intersecting targets were involved in PI3K/Akt pathway and protein processing in endoplasmic reticulum,etc.CONCLUSION The endoplasmic reticu-lum stress in cerebral ischemic stroke is related to the bi-ological processes of reaction to oxidative stress,the reg-ulation of neuron death,and negative regulation of cell differentiation,the mechanism may be related to neuroin-flammation and apoptosis.

Role of free radicals in cerebral ischemic tolerance of rats induced by limb ischemic preconditioning / 中国病理生理杂志

AIM: To explore whether free radicals participate in cerebral ischemic tolerance and the up-regula-tion of p38 MAPK and ERK signaling pathways in rats induced by limb ischemic preconditioning (LIP). METHODS: A total of 128 Wistar rats with permanent occlusion of bilateral vertebral arteries were randomly divided into sham group (n=16), cerebral ischemia (CI) group (n=16), LIP+CI group (n=16), DMTU (a free radical scavenger)+LIP+CI group (n=64) and DMTU+sham group (n=16). Six rats in each group were used to observe the delayed neuronal death (DND) in hippocampal CA1 region by thionin staining at 7 d after the end of operation. Other 10 rats in each group were used to de-tect the expression of p38 MAPK and ERK in hippocampal CA1 region by immunohistochemistry and Western blot. RE-SULTS: Lethal CI resulted in obvious DND in hippocampal CA1 region. However, LIP reversed the above injurious changes, represented by the decrease in histological grade and the increase in neuronal density compared with CI group (P<0. 01). Moreover, LIP significantly up-regulated the expression of p38 MAPK and ERK in hippocampal CA1 region com-pared with CI group (P<0. 01). Administration of free radical scavenger DMTU via femoral vein before LIP partially re-versed the neuroprotective effect of LIP, and blocked the up-regulation of p38 MAPK and ERK expression in hippocampal CA1 region in rats compared with LIP+CI group (P<0. 01). CONCLUSION: Free radicals are involved in the neuropro-tection and up-regulation of p38 MAPK and ERK expression induced by LIP in rats.

Tonic Traditional Chinese Medicine Injections Against Cerebral Ischemic Stroke： An Overview of Systematic Reviews/Meta-analyses / 中国实验方剂学杂志

ObjectiveTo re-evaluate the systematic reviews/Meta-analyses （SRs/MAs） of tonic traditional Chinese medicine （TCM） injections against cerebral ischemic stroke （CIS） and provide evidence support for clinical practice and decision-making. MethodTCM injections of different varieties were obtained after searching the three major drug catalogues. Seven Chinese and English databases were searched from database inception to March 13，2022，for the relevant SRs/MAs. The methodological quality，risk of bias，reporting quality，and quality of evidence were assessed by Assessment of Multiple Systematic Reviews-2 （AMSTAR-2），the Risk of Bias in Systematic Review （ROBIS），the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 （PRISMA 2020），and the Grading of Recommendations Assessment，Development，and Evaluation （GRADE）. In addition，the literature overlap matrix was established to calculate the corrected covered area （CCA） and evaluate the rate of overlaps of the original literature. ResultFive types of TCM injections and 18 SRs/MAs were included. AMSTAR 2 evaluation showed that the methodological quality of 18 SRs/MAs was extremely low，and 14 SRs/MAs had a high risk of bias assessed by ROBIS. The quality evaluation results reported by the PRISMA 2020 showed that the scores of the studies included ranged from 19.5 to 28.5，with 10 being of medium quality and eight of low quality. The evaluation with the GRADE system demonstrated that one outcome was moderate-quality evidence，15 outcomes were low-quality evidence，and 41 outcomes were very low-quality evidence. The CCA of the included SRs/MAs was 0.263，indicating a low rate of overlaps of the original literature. ConclusionTonic TCM injections are effective and safe in the treatment of CIS，but this conclusion should be treated with caution because of the low quality of methodology，reports，and evidence in published SRs/MAs. It is recommended to improve the study design，obtain clinical evidence of higher quality，and conduct systematic evaluations in strict accordance with procedures to standardize the reporting of research results.

Anemia and risk of periprocedural cerebral injury detected by diffusion-weighted magnetic resonance imaging in patients undergoing transcatheter aortic valve replacement / 世界急诊医学杂志（英文）

@#BACKGROUND: Anemia is prevalent in patients undergoing transcatheter aortic valve replacement (TAVR) and has been linked to impaired outcomes after the procedure. Few studies have evaluated the impact of anemia and new ischemic lesions post TAVR. METHODS: We prospectively enrolled 158 patients who received TAVR in our center. Anemia was defined according to the World Health Organization criteria as hemoglobin <12 g/dL in women and <13 g/dL in men. All patients underwent diffusion-weighted magnetic resonance imaging (DW-MRI) procedure before and within 4-7 days after TAVR. RESULTS: Anemia was present in 85 (53.8%) patients who underwent TAVR, and 126 (79.7%) patients had 718 new DW-MRI positive lesions with a mean of 4.54±5.26 lesions per patient. The incidence of new ischemic lesions was 81.2% in patients with anemia versus 78.1% in patients without anemia (P=0.629). Moreover, anemic patients had bigger total volume/lesions in the anterior cerebral artery/middle cerebral artery (ACA/MCA) and MCA regions compared to the non-anemic patients (31.89±55.78 mm 3 vs. 17.08±37.39 mm3, P=0.049; and 54.54±74.72 mm 3 vs. 33.75±46.03 mm3, P=0.034). Anemia was independently associated with the volume/lesion in the ACA/MCA (β=16.796, 95% confidence interval [95% CI] 2.001 to 31.591, P=0.026) and in the MCA zone (β=0.020, 95% CI 0.001 to 0.040, P=0.041). CONCLUSIONS: Patients with pre-procedural anemia may have bigger total volume/lesions in the ACA/MCA and MCA regions compared to the non-anemic patients. Whether the consequences of bigger total volume/lesions impact neurological and cognitive outcomes remains to be investigated.

Danshen-Chuanxiongqin Injection attenuates cerebral ischemic stroke by inhibiting neuroinflammation via the TLR2/ TLR4-MyD88-NF-κB Pathway in tMCAO mice / 中国天然药物

Danshen-Chuanxiongqin Injection (DCI) is a commonly used traditional Chinese medicine for the treatment of cerebral ischemic stroke in China. However, its underlying mechanisms remain completely understood. The current study was designed to explore the protective mechanisms of DCI against cerebral ischemic stroke through integrating whole-transcriptome sequencing coupled with network pharmacology analysis. First, using a mouse model of cerebral ischemic stroke by transient middle cerebral artery occlusion (tMCAO), we found that DCI (4.10 mL·kg

Network pharmacology predicts the mechanism and related experimental research on the effective components of Salvia miltiorrhiza and Carthamus tinctorius against cerebral ischemic stroke / 西安交通大学学报(医学版)

【Objective】 To explore the effect mechanism of Salvia miltiorrhiza and safflower on combined anti-ischemic stroke and verify relevant action targets in middle cerebral artery occlusion (MCAO) rat model based on network pharmacology. 【Methods】 ①Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards databases were used to screen the active components, component targets and ischemic stroke targets of Salvia miltiorrhiza and safflower respectively. The above data were imported into STRING database for protein interaction network analysis, and Cytoscape3.8.0 software was used to construct protein interaction network (PPI) and component target interaction network. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation analysis of target genes were performed using David online analysis tool. ② In this experiment, a rat model of ischemic stroke was prepared by using improved MCAO method, and immunohistochemical method and Real-time quantitative polymerase chain reaction (REAL-TIME PCR) to detect the positive expressions of NLRP3 inflammatory body and NF P65 protein in the brain tissue of rats in each group so as to explore the functional mechanism of anti-inflammation reaction against cerebral ischemia injury. 【Results】 ① A total of 87 effective components, corresponding to 253 targets, 1448 targets for ischemic stroke and 161 targets related to drugs and diseases, were screened from the Salvia milticorrhiza and safflower drug pairs. We obtained 730 biological processes, 81 cell components and 128 molecular functions through GO analysis, and 127 signal pathways through KEGG analysis. ②Immunohistochemical method and Real-time PCR determination results showed that compared with control group rats, model group rats had significantly increased tissue NLRP3 inflammatory body and NFkBp65 protein expressions (P<0.01). Compared with those in the model group, NLRP3 inflammatory body and NFkBp65 protein expressions significantly decreased in Dan red compatibility groups and nim horizon groups (P<0.01). 【Conclusion】 Compatibility of effective components in salvia miltiorrhiza, and carthamus tinctorius can further downregulate the release of inflammatory corpuscle NLRP3 through NFkB signaling pathway by blocking inflammatory lesions and thus plays the role of fighting against inflammatory damage.

Influence of acupuncture combined with rehabilitation therapy on limb motor function and serum cAMP and cGMP in patients with hemiplegia of cerebral ischemic stroke / 中国针灸

OBJECTIVE@#To evaluate the therapeutic effect of the combined treatment with balance acupuncture therapy and exercise re-learning rehabilitation therapy and the impact on serum cAMP and cGMP in the patients with hemiplegia of cerebral ischemic stroke.@*METHODS@#A total of 90 patients of hemiplegia of cerebral ischemic stroke were randomized into an observation group and a control group, 45 cases in each one. All of the patients in the two groups received health education, diet guidance, routine symptomatic treatment as well as exercise re-learning rehabilitation therapy. Additionally, in the observation group, balance acupuncture therapy was applied, in which, the acupoints on the aspect of the human body, on the governor vessel and bladder meridian were adopted in the morning and those on the aspect of the human body, on the conception vessel and kidney meridian were stimulated in the afternoon. In the control group, the regular acupuncture was given. In the two groups, both acupuncture and rehabilitation therapies were given 5 days a week, 2 week-treatment as one course and totally 2 courses were required. Separately, before and after treatment, the score of Fugl-Meyer assessment (FMA) and the score of Chinese stroke scale (CSS) were recorded, the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) detected in serum and the clinical therapeutic effect were evaluated in the two groups.@*RESULTS@#After treatment, FMA score was increased in the patients of either of the groups as compared with that before treatment (<0.01) and CSS score decreased as compared with that before treatment (<0.01). After treatment, FMA score in the observation group was higher than that in the control group (<0.01) and CSS score was lower than the control group (<0.01). After treatment, the level of serum cAMP of the patients in either of the groups was increased as compared with that before treatment (<0.01) and that of cGMP decreased as compared with that before treatment (<0.01). After treatment, the level of cAMP in the observation group was higher than that in the control group (<0.01) and that of cGMP was lower than the control group (<0.01). The total effective rate was 93.3% (42/45) in the observation group, better than 73.3% (33/45) in the control group (<0.01).@*CONCLUSION@#The balance acupuncture therapy combined with exercise re-learning rehabilitation effectively improves the motor function of the affected limb, relieves injury and regulate the levels of serum cAMP and cGMP in the patients with hemiplegia of ischemic stroke.

Mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos Component Compatibility on Inflammatory Factor in Brain Tissue of Rats with Ischemic Stroke / 中国实验方剂学杂志

Objective:This study intends to study the regulatory effect and mechanism of the effective components of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos on inflammatory factors related to cerebral ischemia-reperfusion injury in rats through multiple levels of neuropathology， molecular neurobiology and functional behavior. Method:The 32 male rats were randomly divided into four groups： sham group， model group， Danhong components compatibility group（720 mg·kg-1）， nimodipine （0.5 mg·kg-1）groups，each group of eight male rats.Cerebral ischemia was established by middle cerebral artery occlusion （MCAO） approach. The treatment was performed immediately and at 6 hour after MCAO.Hematoxylin-eosin （HE）staining was used to check the changes of brain histopathology， immunohistochemistry and Real time polymerase chain reaction （Real-time PCR） were used to check the expression of IL-1β and Nrf2 in brain tissue，Western blot was used to detect the protein expression of Nrf2 in brain tissue. The aim is to investigate the treatment mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos components in a rat model of cerebral ischemic-reperfusion injury. Result:HE staining results showed， compared with sham group， the surviving neurons amount in the model group was significantly reduced（P<0.01），compared with the MCAO group，the number of surviving neurons in the brain tissue of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos component compatibility group and nimodipine group was significantly increased（P<0.05，P<0.01）.The results of immunohistochemistry and Real-time PCR showed that，compared with normal group，IL-1β and Nrf2 expression in model group were significantly increased （P<0.01），compared with MCAO group， the expression of IL-1β and Nrf2 in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos component compatibility group and the nimodipine group was significantly decreased （P<0.05，P<0.01）. Western blot results showed that， compared with sham group， Nrf2 positive expression in model group was much more increased （P<0.01）， compared with MCAO group， the expression of Nrf2 in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos component compatibility group and the nimodipine group was significantly decreased （P<0.01）. Conclusion:The combination of effective components of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos can significantly down-regulate the expression of IL-1β and Nrf2 proteins.The mechanism is to activate the protein expression of inflammatory pathways， reduce the apoptosis of nerve cells， and finally inhibit the inflammatory response in the process of ischemic stroke injury.

The effects of bone marrow mesenchymal stem cells on the expression of nerve growth factor and caspase-3 after cardiac arrest in the rats / 中华急诊医学杂志

Objective To investigate the effects of bone marrow mesenchymal stem cells (BMSCs) transplantation on the expression of nerve growth factor (NGF) and Caspase-3 in rat hippocampus after cardiac arrest (CA). Methods Sprague-Dawley (SD) rats were randomly divided into 3 groups: sham group (n=6), CA group (n=6), and BMSCs group (n=6). CPR was performed on the groups after the induction of asphyxial cardiac arrest. Animals in the BMSCs group or the CA group were respectively injected with a dose of 1×106 BMSCs in 0.5 mL phosphate buffer solution (PBS) or 0.5 mL PBS alone via the vena caudalis 1 h after successful resuscitation. The neurological status after restoration of spontaneous circulation (ROSC) were assessed by modified neurological severity scores (mNSS); serum levels of S100B were assayed, and the expression of NGF and Caspase-3 in hippocampus was detected by immunohistochemistry. Results Compared with the CA group, mNSS and S100B levels were lower in the BMSCs group on the 7th day after ROSC [(0.9±0.3) vs (4.5±0.6), (90.12±4.62) pg/mL vs (182.30±2.58) pg/mL, both P<0.05] with higher expression of NGF and lower expression of Caspase-3 [(11.391±1.297) vs (7.744±1.334), (6.256±1.036) vs (8.506±1.742), both P< 0.05]. Conclusions BMSCs transplantation might improve rat's neurological functions after cardiac arrest, which may be related to up-regulation of NGF expression and down-regulation of Caspase-3 expression.

Effect of Yiqi Huoxue Recipe on Oxidative Stress Response in Rats with Cerebral Ischemia Injury Based on Nrf2/HO-1 Signaling Pathway / 中国实验方剂学杂志

Objective:To investigate the protective effect of Yiqi Huoxue recipe on rats with cerebral ischemia injury by using oxidative stress injury as an entry point. Method:SD rats were randomly divided into model group, sham operation group, nimodipine group (20 mg·kg-1), Yiqi Huoxue recipe high, medium and low dose group (2.916,1.458,0.729 g·kg-1). After 14 days of stomach, acute cerebral ischemic injury model was established by ligation of bilateral common carotid arteries. Ultrasound of synapse was observed by transmission electron microscopy. Total superoxide dismutase (T-SOD) and dialdehyde (MDA), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), horizontal adenine nucleoside triphosphate (ATP) levels were detected by biochemical method. Western blot and Real-time PCR was used to determine the expression of heme oxygenase-1(HO-1) and nuclear factor E2-related factor 2 (Nrf2) protein and mRNA in the ischemic cortex of rats. Result:Transmission electron microscopy showed that Yiqi Huoxue recipe had a significant improvement on the degree of cerebral ischemic injury. Compared with sham operation group, MDA levels in the brain homogenate of model group increased significantly, T-SOD and GSH-Px levels were significantly decreased (P+-K+-ATP ase, Ca2+-Mg2+-ATP ase and ATP was significantly decreased (PPPPP+-K+-ATP ase, Ca2+-Mg2+-ATP ase and total ATP activity(PPPPPPConclusion:Yiqi Huoxue recipe may protect against cerebral ischemic injury by inhibiting oxidative stress through Nrf2/HO-1 signaling pathway.

Two-photon in vivo imaging of blood brain barrier injury in the ultra-early stage of cerebral ischemic stroke / 上海交通大学学报（医学版）

Objective: To evaluate the effect of two-photon in vivo imaging on detecting the blood brain barrier (BBB) injury in the ultra-early stage of cerebral ischemic stroke. Methods: Twelve clean grade C57BL/6 healthy male mice aged 8-12 weeks were randomly divided into Sham group and middle cerebral artery occlusion (MCAO) group,which were sham operated or middle cerebral artery occluded,respectively. After 60 min of ischemia,MCAO mice were treated with reperfusion for 30-60 min after the suture being removed. The vessels and the neutrophils of mice in the two groups were labeled intravenously with Alexa-Fluora-488 conjugated dextran and rhodamine 6G,respectively. The integrity of BBB was detected by intravenous injection of tetramethylrhodamine-5-maleimide (TMR). Before and after the stroke,the real-time changes of the fluorescence intensity of the inside and outside cerebral vessels of mice in the MCAO group were observed by two-photon fluorescence microscopy. Results: The fluorescence intensity of TMR in the external cerebrovascular of mice in the MACO group was significantly increased within 30-60 min after stroke (P=0.000),suggesting there existed tracer leakage. Compared with the Sham group,the movement of neutrophils in the blood vessels of mice in the MACO group was significantly slowed down (P=0.000). Conclusion: Two-photon in vivo imaging can be used to detect the BBB injury in the ultra-early stage of cerebral ischemic stroke,which provides a certain reference value for clinical application.

Tau protein expression and possible reasons in Beagle dog model of chronic ischemic cerebral white matter dysmyelination / 重庆医学

Objective To explore the expression level and possible reasons of Tau protein in Beagle dog model of ischemic cerebral white matter(WM) demylination.Methods Sixteen adult Beagle dogs were divided into the sham operation group(A) and observation group B,C and D according to the completely random mumber table method,4 cases in each group.Different.degrees of cerebral ischemia animal models were established by 4-vessel occlusion(4-VO) method.The bilateral ventricle edge white matter (WM) was selected.The oligodendrocyte precursors(OPCs) were labeled by NG2.The mature oligodendrocytes(Ols) were labeled by CNPase.Tau,NG2 and CNPase were detected by using the immunohistochemical method.The expression level was quantified by the mean optical value.The correlation among Tau,NG2 and CNGase was analyzed by adopting the Pearson linear correlation analysis.Results The HE staining showed obvious changes of WM demylination after chronic cerebral ischemic.The scores after LFB staining in the group A,B,C and D were(0.75 ± 0.71) points,(1.38 ± 0.06) points,(1.63 ± 0.52) points and (1.88 ± 0.64)points.Compared with the group A,the scores in the group B,C and D were much higher(P＜0.05).Compared with the group A,the expression levels of Tau protein and NG2 were significantly increased(P＜0.05),while the CNPase expression level was significantly decreased(P＜0.05).The Pearson correlation analysis showed that Tau expression level was positively correlated with the NG2 expression level(r=0.277,P=0.006);Tau and NG2 were negatively correlated with the CNPase level(r=-0.303,-0.402,P=0.003,0.001).Conclusion The increase of Tau expression in Beagle dog model of ischemic cerebral WM demylination may be related to the differentiation dysmaturity of OPCs.

The effects of paired associative stimulation of tibial nerve-M1 cortex on forelimb dysfunction in rats with cerebral ischemic stroke and the underlying mechanisms / 中华物理医学与康复杂志

Objective To explore the effects and the underlying mechanisms by which paired associative stimulation ( PAS) of tibial nerve electrostimulation and M1 cortex transcranial magnetic stimulation ( TMS) in pro-moting the recovery of forelimb dysfunction in rats with cerebral ischemic stroke. Methods Resting motor thresholds of left extensor carpi radialis muscle ( ECR) were determined 5 min before and 5 min, 30 min, 60 min after PAS,respectively, in 8 male Sprague-Dawley ( SD) rats. Then 48 male SD rats were divided into a sham group ( n=16) subject to sham surgery, an experimental group (n=32) which was further divided into a MCAO group (n=16) and a PAS group (n=16) after cerebral ischemic stroke model was established successfully by occluding the right middle cerebral artery. 24 hours after surgery, PAS consisting of left tibial nerve stimulation and right M1 cortex area TMS was applied to PAS group once daily for 7 consecutive days. The corner tests and grip strength tests were per-formed before and after 7 days of PAS treatment in each group. The RMTs of left ECR were determined, metabolites of the left area tissue of cervical spinal cord were measured by nuclear magnetic resonance spectrum, and expressions of Bcl-2 and Bax of left and right area tissue of cervical spinal cord enlargement were detected by Western Blot tech-nique after 7 days of intervention. Results The average RMTs of left ECR at 5 min, 30 min, 60 min after PAS were significantly lower than those at 5 min before PAS ( P<0.05) . All rats in experimental group showed significant higher turning scores and lower grip strength when compared with sham group (P<0.001 or P<0.01). After PAS interven-tion, PAS group demonstrated lower turning scores, higher grip strength and lower RMT of left ECR as compared with MCAO group ( P<0.05 or P<0.01) . The expression of GABA of left cervical enlargment was significantly decreased in MCAO group when compared with the sham group ( P<0.05) , and there was no significant difference between MCAO group and PAS group. Meanwhile, other metabolites showed no significant difference among the three groups. The av-erage expression level of Bcl-2 and Bax proteins in both sides of cervical spinal cord enlargment showed no significant difference among three groups either. Conclusions Tibial nerve-M1 cortex area PAS may increase the excitability of motor cortical representation of forelimbs in rats, by which PAS promotes the recovery of forelimb dysfunction in rats with cerebral ischemic stroke.

Oxidant stress and opoptotic effects of anisodine hydromide on rats with chronic cerebral ischemic injury / 中成药

AIM To observe the oxidant stress and opoptotic effects of anisodine hydromide (AH) on chronic cerebral hypoperfusion (CCH) rats.METHODS In vivo CCH models were established in adult male SpragueDawley rats by permanent ligation of bilateral common carotid arteries [two-vessel occlusion (2-VO)] surgery.Rats were randomly divided into six groups,sham group,model group,positive group of n-butylphthalide and sodium chloride injection,and AH groups (1.2 mg/kg high-dose group,0.6 mg/kg medium-dose group,and 0.3 mg/kg low-dose group).Antioxidant indices including the activity of SOD,CAT,LDH and iNOS and the content of GSH and NO were measured.In the in vitro trial,PC12 cells were divided into control group,model group,positive group of n-butylphthalide,and AH groups (100 μmol/L high-dose group,50 μmol/L mediumdose group,and 25 μmol/L low-dose group),and the hypoxic models were established by treating PC12 cells with CoCl2.The cells had their release of NO and LDH detected,their cellular apoptosis determined by Hochest 33342 fluorescence staining,and the expression of P53 protein identified by IF (immunofluorescence) and Western blotting method.RESULTS The in vivo trial revealed AH's enhancement in serum SOD activity and inhibition in serum iNOS activityof the CCH rats,and its power in the cerebral GSH and LDH release reduction.The in vitro trial showed the resultant lower LDH and NO release,decreased number of neuro-apoptosis,and inhibited P53 pro tein expression after AH intervention.CONCLUSION The antioxidant and antiapoptotic effects of AH on CCH rats may be associated with down regulation of P53 protein.

Protective effect of icaritin on focal cerebral ischemic–reperfusion mice / 中草药·英文版

Objective: To investigate the protective effects of icaritin (ICT), one of the active ingredients in Epimedii Folium, on mouse model of cerebral ischemia-reperfusion (I/R) in vivo. Methods: ICR mice were subjected to an 1 h transient middle cerebral artery occlusion (MCAO) and followed by 24 h of reperfusion. Neurological deficits, infarct volume, brain edema and survive rate were measured, respectively. The levels of brain IL-1β TNF-α ROS and DNA-binding activity of NF-κB p65 were measured by ELISA kits. The levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) were detected by spectrophotometry, and the release of nitric oxide (NO) were detected by Griess kit. Results: ICT markedly reduced the neurological deficit scores, brain edema, infarct volume and increased the survival rate of the cerebral I/R mice. The expression of IL-1β TNF-α NO, MDA and DNA-binding activity of NF-κB p65 were significantly inhibited by ICT, while the activity of SOD were up-regulated at the same time. Conclusion: ICT possessed significant neuroprotective effects in cerebral I/R mice, which might be related to prevent neuroinflammatory and oxidative damage.

Study on pharmacokinetics and pharmacodynamics of ginkgolides in rat model with cerebral ischemia injury / 中草药

Objective To study the metabolic process of ginkgolides in rats with cerebral ischemic injury based on pharmacokinetic- pharmacodynamics (PK-PD) binding model. Methods The middle cerebral artery occlusion (MCAO) model was established by the suture method. After reperfusion, rats were randomly assigned to nasal administration, ig administration, and iv administration group.The orbital blood was taken at different time points of 0.25, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 4.0, 6.0, 9.0, and 12.0 h after the administration of the ginkgolides solution. The drug-time curve of ginkgolide B in plasma were drawn according to the concentration measured by LC-MS. The time-effect curve of superoxide dismutase (SOD) and malondialdehyde (MDA) were drawn based on the value measured by the kit. The pharmacokinetic parameters were calculated by DAS 2.0 software to fit the PK-PD binding model. Results The t1/2 of ginkgolide B of the rats in the administration group was smaller than that in the MCAO model group. The area under the curve (AUC) of nasal administration was significantly higher than intragastric administration and intravenous administration. Conclusion Ginkgolide B has a good protective and mitigating effect on ischemic stroke. The pharmacokinetics of nasal administration is better than iv and ig administration, which can provide reference for the development of nasal administration of ginkgolide B.

Simulation and prediction of material foundation of Puerariae Radix for ischemic stroke based on molecular docking technology / 中草药

Objective To study the mechanism of Puerariae Radix in the treatment of ischemic stroke by using molecular docking technology. Methods The small molecules of Puerariae Radix based on molecular docking technology docked with 21 key targets protein of cerebral ischemic stroke, and multi-component protein target network was established by Cytoscape 3.1.1 software. Results Through virtual screening of molecular docking technology, 28 active small molecules of Puerariae Radix were chosen, 12 of which were novel small molecules, and it identified that 11 of those compounds had strong interactions with no less than 10 targets. Conclusion The molecular docking can be used to find the active components of Puerariae Radix in treatment of cerebral ischemic stroke, which provide a new reference of studying on the multiple ingredients and targets of Chinese materia medica compounds.

Research progress on Chinese materia medica pairs and their active components against cerebral ischemia / 中草药

The in-depth study on the law of drug pair compatibility and its mechanism has important scientific connotation for the clinical prescriptions and the improvement of curative effect. In recent years, many prevention and treatment of cerebral ischemic injury found that the rational use of Chinese materia medica pairs by optimizing the combination of Chinese medicine compound played a multi-target, multi-level role in the ischemic brain tissue of the neurovascular units, multi-channel regulation of the relevant signal pathways, which can significantly reduce the damage of ischemic penumbra brain tissue, relieve the inflammatory cascade and reperfusion injury caused by cerebral ischemia injury, promptly restore the blood flow in the brain and effectively protect the neurons, achieve “re-flow” and “brain protect” similar effects, and further promote the repair of nerve function.

Application of targeted temperature management in the treatment of cardiac arrest in adult patients / 中华危重病急救医学

Cardiac arrest (CA) is a fatal condition with low resuscitation rate and high mortality rate. Most of the survivors have neurological sequelae affecting their quality of life. Targeted temperature management (TTM) has been suggested by a number of studies to increase the survival rate and improve neurological outcome of CA. It is highly recommended by the International Liaison Committee on Resuscitation (ILCOR) for unconscious patients after resuscitation. In this review, we discuss the pathological mechanism of brain injury in CA and applications of TTM in adults with CA, with the aim of providing valuable information for clinical application.