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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.
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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.
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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.
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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.
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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.
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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.
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AIM To investigate the anti-neuroinflammation effects of 4-hydroxybenzyl aldehyde (4-HBAL) from Gastrodia elata Blume on acute cerebral ischemic injury in rats and its nechanism of action.METHODS The rat model of acute cerebral ischemic injury was induced by injecting arachidonic acid via intracarotid artery.Brain tissue samples were taken from the animals 3 h after the model of acute cerebral ischemic injury.Tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were detected in brain tissue to evaluate the effects of 4-HBAL in vivo.Lipopolysaccharid (LPS)-induced activation of BV-2 microglia cells model was used to explore the anti-neuroinflammation mechanism of 4-HBAL.RESULTS The experimental results showed that 4-HBAL had a significant protective effect on acute cerebral ischemic injury.It could significandy decrease the contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β),and obviously inhibit the production of nitric oxide (NO),prostaglandin E2 (PGE2) and TNF-α in LPS-stimulated BV-2 cell,and increase the production of interleukin-10 (IL-10) and transforming growth factors-β (TGF-β) in BV-2 cell.CONCLUSION The mechanism of 4-HBAL may be related to the suppression of the excessive activation of microglia after cerebral ischemia and the promotion of the transformation of microglia into anti-inflammatory phenotype.
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Objective To investigate the preventive effects of Buyang Huanwu Decoction (BYHWD) and its recipe composition (BYJJF) in focal ischemic brain injury condition in vivo/in vitro. Methods In vivo studies, SD rats were divided into sham-operation group, MCAO group, BYHWD group and BYJJF group based on rat weight, 10 rats in each group. The body weight, infarct area and brain water contents were determined. In vitro studies, H2O2 was used to damage PC12 cells, and the vitro oxidative stress cell model was established. PC12 cells were divided into normal group, blank control group, BYHWD and BYJJF groups with different concentrations (0.1, 0.2, 0.5, 1.0, 2.0, 3.5 mg/mL). MTT method was employed to determine the protective effects of BYHWD and BYJJF on model cells.Results Vivo studies showed that after 7 days of treatment with BYHWD and BYJJF, those determinated quotas were all significantly improved compared with MCAO model rats (P0.05).Vtiro studies showed that the protective effects of BYHWD and BYJJF took place 2 hours later, and it was obvious in oxidative stress injury caused by H2O2, with statistical differences with model group (P0.05).Conclusion The research confirmed that BYJJF plays a significant role in improving the cerebral ischemia injury, which is the same performance as BYHWD, and BYJJF can save TCM resources under the precondition of TCM efficacy.
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@#Neural stem cells are a category of cells with self-renewal and differentiation potential. Proliferation and differentiation of neural stem cells have closely relation with growth factor, cell factor, environmental signal, and so on. In recent years, evidence indicates that neural stem cells possessing multipotency naturally occur in adult brain. The found of adult neural stem cells have changed the theory that central nervous system cannot regenerative. Chinese Traditional Medicine can effectively induce adult neural stem cells to proliferate and differentiate, opening up unprecedented direction in the research for the treatment of nerve regeneration, and showing great potency for curing cerebral ischemic injury.
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Objective: To determine if naloxone has reverse effect on cerebral ischemic injury following cardiac arrest. Method:Ten dogs underwent 15-min cardiac arrest and then were divided into two groups during 3-hour cardiopulmonary resuscitation (CPR). Group A(n=5): the animals were administered with conventional CPR;group B(n=5): in addition,at onset of CPR,an I. V. bolus of 0.2mg?kg~(-1) of naloxone,followed by infusion of 0.02mg?kg~(-1)?h~(-1). Result: Cerebral blood flow, Cerebral perfusion pressure in group B were significantly higher than those in group A (P
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AIM To study the role of nitric oxide (NO) and nitric oxide synthase (NOS) inhibitors during the early stage of focal cerebral ischemic injury in rats. METHODS The rat models of middle cerebral artery occlusion were established with the intraluminal suture method. The nonselective NOS inhibitor and selective inducible NOS inhibitor were used for investigating the effects of NO and NOS changes in the focal ischemic brain tissue and their respective roles during the early stage of focal cerebral ischemic injury. RESULTS This study showed that nonselective NOS inhibitors(N G nitro L arginine) aggravated brain damage in the early stage of focal cerebral ischemia and selective iNOS inhibitors (Aminoguanidine )did not significantly improve the brain damage , but could decrease markedly the deterioration of brain damage. CONCLUSION It may be concluded that the NO from defferent cells and types of NOS play unlike roles in the early stage of focal cerebral ischemic injury.