PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) is the main regulatory enzyme for homocysteine metabolism. In the present study, we evaluated whether the MTHFR 677C>T and 1298A>C gene polymorphisms are associated with SBI and plasma homocysteine concentration in a Korean population. MATERIALS AND METHODS: We enrolled 264 patients with SBI and 234 healthy controls in South Korea. Fasting plasma total homocysteine (tHcy) concentrations were measured, and genotype analysis of the MTHFR gene was carried out. RESULTS: The plasma tHcy levels were significantly higher in patients with SBI than in healthy controls. Despite a significant association between the MTHFR 677TT genotype and hyperhomocysteinemia, the MTHFR 677C>T genotypes did not appear to influence susceptibility to SBI. However, odds ratios of the 1298AC and 1298AC + CC genotypes for the 1298AA genotype were significantly different between SBI patients and normal controls. The frequencies of 677C-1298A and 677C-1298C haplotypes were significantly higher in the SBI group than in the control group. CONCLUSION: This study demonstrates that the MTHFR 1298A>C polymorphism is a risk factor for SBI in a Korean population. The genotypes of 677C>T and 1298A>C polymorphisms interact additively, and increase the risk of SBI in Korean subjects.
Aged ; Asian Continental Ancestry Group ; Brain Infarction/*genetics/*metabolism ; Female ; Genotype ; Haplotypes ; Homocysteine/*metabolism ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Middle Aged ; Polymorphism, Genetic/*genetics

OBJECTIVE: To explore the influence of hyperbaric oxygen (HBO) treatment on neural plasticity and it's mechanism in experimental rats with cerebral ischemia. METHODS: Ninety-healthy male adult Sprague-Dawley rats (3 to approximately 4 month old) were randomly divided into a pseudo-operative group, a model group, and an HBO therapy group. The middle cerebral artery occlusion model was duplicated with suture methods, then we used beam walking test (BWT) to determine the motor skill of the rats and immunohistochemistry method to detect the distribution and location of microtubule-associated protein-2 (MAP-2) and glial fibrillary acidic protein (GFAP). Quantitative real-time PCR was used to detect the expression of Map-2 mRNA and GFAP mRNA. RESULTS: Immunohistochemistry showed that the fluorescence gray scale value of Map-2 in the HBO group was the highest in 3 groups at 1st week and 2nd week (P<0.05).The value of GFAP was lower than that of the model group but higher than that of the sham operated group (P<0.05). Real-time fluorescence-quantitative PCR indicated that the Map-2 mRNA of HBO group was the highest in 3 groups at 1st week and 2nd week (P<0.05); but the value of GFAP mRNA in the HBO group is lower than that of the model group,but higher than that of the sham operated group at 1st week and 2nd week (P<0.05). CONCLUSION After cerebral infarction, giving hyperbaric oxygenation treatment can improve the limbs motor function, and hyperbaric oxygenation treatment can increase the expression of Map-2 and decrease the expression of GFAP, which promote neural plasticity.
Animals ; Brain Infarction ; physiopathology ; therapy ; Glial Fibrillary Acidic Protein ; genetics ; metabolism ; Hyperbaric Oxygenation ; Infarction, Middle Cerebral Artery ; physiopathology ; therapy ; Male ; Microtubule-Associated Proteins ; genetics ; metabolism ; Neuronal Plasticity ; drug effects ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

In order to provide a complete picture of pathogenesis in cerebral ischemia, cerebral cortex in MCAO rats were analysed for alteration in their proteomes. Comparative proteome analysis was used to compare signal corresponding to individual cerebral cortex proteins on a two-dimensional gel between MCAO rats and the normal control (NC) group. After sample preparation, two-dimensional electroghoresis separated proteins were stained with Commassie Brilliant Blue. The image data were analyzed on a Dell computer using Image Master v 3.01 software. In cerebral cortex, 30 proteins were differentially expressed in MCAO rats compared with NC. There were 11 spots significantly increased, 15 spots significantly decreased and Adenylate kinase isoenzyme 1 was detected only in NC group, biliverdin reductase B, small inducible cytokine A4 [Precursor] only in MCAO group. Peroxiredoxin 2 divided into two points in MCAO6h group. In the end, this approach may lay a foundation for the further investigation of pathogenic mechanisms in cerebral ischmic injury.
Animals ; Brain Ischemia ; genetics ; metabolism ; Cerebral Cortex ; metabolism ; Electrophoresis, Gel, Two-Dimensional ; Gene Expression Profiling ; Infarction, Middle Cerebral Artery ; genetics ; metabolism ; Nerve Tissue Proteins ; chemistry ; genetics ; metabolism ; Proteome ; Proteomics ; methods ; Random Allocation ; Rats ; Rats, Wistar

Vascular endothelial growth factor is a potent inducer of angiogenesis identified in recent years, and its relationship with ischemic cerebral vascular diseases is a hotspot for many investigators at present. In this review, we focus on the recent evidence for VEGF expression, biological effect and its role in the treatment and prognostication of ischemic cerebral vascular disease.
Angiogenesis Inducing Agents ; therapeutic use ; Brain Ischemia ; drug therapy ; metabolism ; Cerebral Infarction ; drug therapy ; metabolism ; Humans ; Neovascularization, Physiologic ; drug effects ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics ; therapeutic use

OBJECTIVETo discuss the protective effect of Mailuoning injection on ischemia/reperfusion (I/R) injury in rats and its mechanism.

METHODHealthy male adult Sprague-Dawley (SD) rats were randomly divided into the sham operation group, the model group, the edaravone (3 mg x kg(-1)) control group, and Mailuoning high, middle and low-dose groups (4, 2, 1 mL x kg(-1)), with 10 rats in each group, and administered with drugs through tail intravenous injection. The middle cerebral artery occlusion (MCAO) was adopted to establish the rat ischemia/reperfusion model. After the ischemia for 2 h and reperfusion for 24 h, the pathological changes in neurovascular units (NVU) of brain tissues at the ischemia side was observed by HE staining. The expressions of glialfibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Ibal) were detected by the immunohistochemical method. The expressions of tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were detected by the western blotting technique.

RESULTMailuoning injection could significantly improve the pathological changes in cortical penumbra brain tissue UVN of (I/R) rats, reduce the number of GFAP and Ibal positive cells, and significantly decrease the expressions of TNF-alpha, IL-1beta, VCAM-1 and ICAM-1 of brain tissues of I/R rats.

CONCLUSIONMailuoning injection shows an obvious protective effect on UVN of I/R rats. Its mechanism may involve the inhibition of the activation of astrocyte and microglia and the secretion and expression of various inflammatory factors.

Animals ; Brain ; drug effects ; metabolism ; Brain Ischemia ; surgery ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Infarction, Middle Cerebral Artery ; genetics ; metabolism ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Male ; Protective Agents ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; genetics ; metabolism ; prevention & control ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Vascular Cell Adhesion Molecule-1 ; genetics ; metabolism

OBJECTIVETo explore the mechanism of acupoint sticking of "Hua yutie" in improving ischemic stroke.

METHODSEighty rats were randomly divided into 5 groups, a model group, an acupoint sticking group, an acupuncture group, a Nimodipine group and a normal group. Middle cerebral artery occlusion (MCAO) was used for preparation of focal cerebral ischemic rat model. After modeling, any treatment was not given to the model group; for the acupoint sticking group, "Hua yutie" was applied at "Dazhui" (GV 14) ,"Qihai" (CV 6) and "Mingmen" (GV 4); for the acupuncture group, acupuncture was given at the same acupoints as those in the acupoint sticking group; the Nimodipine group received intragastric administration of Nimodipine. And the normal group did not receive any treatment. Their infarction volume, the cerebral water content, expression of vascular endothelial growth factor (VEGF) and the protein level were observed.

RESULTSThe infarction volume coincided with the dominative scope of the middle cerebral artery of the electric coagulation. There were significant differences in the cerebral water content as the various treatment groups compared with that of the model group (all P<0.05). The VEGF positive cell number and the protein level around the infarction area in the acupoint sticking group were increased as compared with those in the model group (P<0.01), with no significant difference as compared with the Nimodipine group and the acupuncture group (all P>0.05).

CONCLUSIONAcupoint sticking of "Hua yutie" alleviates the cerebral damage after ischemia possibly through enhancing the expression and protein level of VEGF.

Acupuncture Points ; Administration, Cutaneous ; Animals ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; Cerebral Infarction ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Gene Expression ; drug effects ; Humans ; Male ; Rats ; Rats, Wistar ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

Pretreatment with brain-derived neurotrophic factor (BDNF) reduces ischemic damage after focal cerebral ischemia, and bone marrow mesenchymal stem cells(MSCs) were reported to ameliorate functional deficits after stroke in rats. Here we investigate the synergistically therapeutic effects of BDNF gene-modified MSCs on cerebral infarction. We transfected MSCs with the BDNF gene using a lentivirus-based system and investigated whether the BDNF-modified MSCs contributed to improved functional recovery in a rat transient middle cerebral artery occlusion (MCAO) model. Compared to untreated rats, rats that received both MSCs and BDNF-MSCs showed significantly more functional recovery. The difference in modified neurological severity score(mNSS) was statistically significant (P < 0.001). Recovery was better in BDNF-MSCs than in MSCs (P < 0.001). At the second week and second month after the systemic delivery of blank vector-modified MSCs and BDNF-modified MSCs, the treated rats exhibited more significant recovery than the control, including the accumulation and living of enhanced green fluorescence protein (EGFP)-positive cells in the infarct area and surrounding areas, neuron-like changes, expression of surface markers of neural cells, and a large amount of BDNF expression in the BDNF-MSCs-treated group. Our findings suggest that BDNF-gene-modified rMSCs can migrate to surrounding areas of the cerebral infarction lesion, differentiate into neural cells, and survive for extended periods. With the synergy of BDNF, they may promote the recovery of the neurological function following cerebral infarction and represent a new strategy for stem cell-based therapy.
Animals ; Brain-Derived Neurotrophic Factor ; biosynthesis ; genetics ; Genetic Vectors ; genetics ; Infarction, Middle Cerebral Artery ; genetics ; therapy ; Lentivirus ; genetics ; metabolism ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Rats ; Rats, Inbred F344 ; Recovery of Function ; Transfection

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
Brain Ischemia/genetics* ; Drugs, Chinese Herbal ; Humans ; Infarction, Middle Cerebral Artery/genetics* ; Ischemic Stroke ; Myeloid Differentiation Factor 88/genetics* ; NF-kappa B/metabolism* ; Stroke/genetics* ; Toll-Like Receptor 2 ; Toll-Like Receptor 4/metabolism*

OBJECTIVETo observe the therapeutic angiogenesis effect of naotai recipe (NR) on local ischemia/reperfusion (I/R) injury of rats by observing signaling pathway of hypoxia-inducible factor-lα (HIF-1α) and vascular endothelial growth factor (VEGF).

METHODSTotally 120 Sprague-Dawley (SD) rats were randomly divided into 4 groups, namely, the normal control group (n =12), the sham-operation group (n =12), the I/R model group (n =48), and the NR group (n =48). Cerebral I/R injury models were established using thread suture method. Rats in the I/R model group and the NR group were sub-divided into 4 sub-groups according to the 1st, 3rd, 5th, and 7th I/R day (n =12). The phenomenon of neovasculization was observed by immunofluorescence staining. The protein and mRNA expression levels of HIF-la, VEGF-A, and VEGFR II receptor were detected by RT-PCR.

RESULTSThere were a large amount of labels for neovasculization in the ischemic area of the NR group. Double-immunofluorescence labeling [vWF (red) and BrdU (green)] was observed in the NR group. Compared with the model group, the HIF-1α protein expression was obviously enhanced on the 1 st day of I/R (P <0.01), and the VEGF protein expression started to enhance on the 3rd day in the NR group (P <0.01). The VEGFR protein expression level was the highest in the NR group on the 5th day of I/R (P <0.01). The protein expression of VEGF and HIF-1α started to decrease on the 7th day of I/R.

CONCLUSIONNR could strengthen angiogenesis after I/R by elevating the expression of HIF-lα and activating HIF-lα/VEGF signaling pathway.

Animals ; Brain Ischemia ; metabolism ; Cerebral Infarction ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Hypoxia-Ischemia, Brain ; metabolism ; Ischemia ; Neovascularization, Pathologic ; Rats, Sprague-Dawley ; Reperfusion Injury ; Signal Transduction ; Vascular Endothelial Growth Factor A ; biosynthesis

OBJECTIVETo explore the changes of endostatin (a strong anti-angiogenesis factor) and vascular endothelial growth factor (VEGF) in the brain tissues of rabbits following cerebral ischemia induced by middle cerebral artery occlusion (MCAO).

METHODSTwenty-four New Zealand white rabbits were randomly divided into 5 groups: control (n = 5), sham-operation (n = 4), 2-hour ischemia (n = 5), 24-hour ischemia (n = 5), and 48-hour ischemia (n = 5). The expression of VEGF and endostatin were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. In situ hybridization was used to characterize the expression of mRNA for the endostatin.

RESULTSBoth the protein (at least 50%, P < 0.01) and mRNA (at least 70%, P < 0.05) of endostatin increased significantly in the ischemic brain tissues after MCAO compared with the control group. VEGF increased at least 270% in the brain after cerebral ischemia (P < 0.05).

CONCLUSIONCerebral ischemia leads to an up-regulation of endostatin in the brain, which is not associated with the increase of VEGF in the brain. The increase of endostatin may serve as a deleterious mechanism for ischemic injury through blocking angiogenesis.

Animals ; Brain ; metabolism ; physiopathology ; Brain Ischemia ; genetics ; metabolism ; physiopathology ; Cerebral Arteries ; metabolism ; Endostatins ; genetics ; metabolism ; Endothelium, Vascular ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Immunohistochemistry ; In Situ Hybridization ; Infarction, Middle Cerebral Artery ; genetics ; metabolism ; physiopathology ; Male ; Neovascularization, Physiologic ; physiology ; Rabbits ; Up-Regulation ; physiology ; Vascular Endothelial Growth Factor A ; metabolism