Focal Cerebral Ischaemia (focal + cerebral_ischaemia)

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Selected Abstracts


MODULATION OF SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STAT) FACTOR PATHWAYS DURING FOCAL CEREBRAL ISCHAEMIA: A GENE EXPRESSION ARRAY STUDY IN RAT HIPPOCAMPUS AFTER MIDDLE CEREBRAL ARTERY OCCLUSION

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2007
Sheng-Li Sun
SUMMARY 1Signal transducers and activators of transcription (STAT) factors are a family of transcription factors that mediate intracellular signalling initiated at cytokine cell surface receptors and transmitted to the nucleus. In the present study, we determined the global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion using microarray analysis. 2The present study used middle cerebral artery occlusion (MCAO) to induce ischaemia and reperfusion in Sprague-Dawley rats. Using superarray Q series Janus tyrosine kinases (Jak)/STAT signalling pathway gene array, a total of 96 genes was screened in adult male rat hippocampus after transient focal cerebral ischaemia. 3The results showed that 23 genes were upregulated at least twofold by ischaemia treatment and that 12 genes were downregulated at least threefold by ischaemia treatment compared with controls. 4After confirmation by quantitative real-time polymerase chain reaction, the data suggest that the gene expression of STAT2, 5a, 5b, 6 and suppressor of cytokine signalling (SOCS) 4 was increased by ischaemia, probably due to a compensatory response of the brain, which may play a protective role in damaged brain tissue. 5The results of the present study provide evidence on global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion, in which STAT2, 5a, 5b, 6 and SOCS4 were confirmed to be significantly modulated during focal cerebral ischaemia. [source]


Effect of continuous infusion of asialoerythropoietin on short-term changes in infarct volume, penumbra apoptosis and behaviour following middle cerebral artery occlusion in rats

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2 2010
Chrystal D Price
Summary 1. Asialoerythropoietin (aEPO), a derivative of cytokine erythropoietin, has been shown to have neuroprotective effects without haematological complications when administered in single or repeated doses. The present study examines our hypothesis that aEPO may provide neuroprotection against programmed apoptotic cell death when administered in a continuous low dose. 2. Focal cerebral ischaemia was introduced by occlusion of the middle cerebral artery using a surgically placed intraluminal filament in young male Sprague Dawley rats (9 weeks old). After 90 min ischaemia, reperfusion was established by filament removal. Both study and control groups had implanted osmotic minipumps through which they received either aEPO (1 ,L/h; 20 ,g/kg per 24 h) or normal saline (1 ,L/h) for 4 days. On Day 4, infarct volume, the number of apoptotic cells and concentrations of activated caspase 3 and 9 were evaluated in the penumbra region. 3. Asialoerythropoietin was detected in the cerebrospinal fluid of the study group, whereas none was detected in the control group. Although there were no significant changes in haematocrit levels or behaviour scores (on Days 1 and 4) between the study and control groups, aEPO administration significantly reduced infarct volume in the study group compared with the control group (168 ± 19 vs 249 ± 28 mm3, respectively; P < 0.05). 4. The number of terminal deoxyribonucleotidyl transferase-mediated dUTP,digoxigenin nick end-labelling (TUNEL)-positive cells and the concentration of activated caspase 3 and 9 in the penumbra region were significantly lower in the study group compared with the control group. 5. In conclusion, our data suggest that aEPO provides a short-term, possibly histological, protection in young adult male rats when administered immediately after reperfusion. [source]


Pretreatment with the ciclosporin derivative NIM811 reduces delayed neuronal death in the hippocampus after transient forebrain ischaemia

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2010
Masaaki Hokari Dr
Abstract Objectives There have been several previous studies showing that ciclosporin, a ligand for cyclophilin D (CypD), reduces mitochondrial permeability transition (mPT) and ameliorates delayed neuronal death. NIM811 is a non-immunosuppressive ciclosporin derivative that also inhibits mPT, but has significantly less cytotoxicity than ciclosporin. Actually, in animal experiments, several investigators have reported that NIM811 ameliorates central nervous system disorders, such as traumatic brain injury, transient focal cerebral ischaemia and spinal cord injury. Therefore, we evaluated whether the ciclosporin derivative, NIM811 reduces mPT and ameliorates delayed neuronal death in the hippocampal CA1 sectors in mice when subjected to transient forebrain ischaemia. Methods Male C57BL/6 mice were treated with 50 mg/kg ciclosporin, 10, 50 or 100 mg/kg NIM811 or phosphate-buffered saline. At 30 min post-injection, all mice were subjected to 20 min bilateral common carotid artery occlusion (BCCAO). To estimate delayed neuronal death, the sections were prepared for HE staining and terminal deoxynucleotidyl transferase-mediated dUTP end-labelling (TUNEL) staining at 72 h after 20 min BCCAO. Furthermore, using 5,5,,6,6,-tetrachloro-1,1,,3,3,-tetraethylbenzimidazolocarbocyanine iodide (JC-1) staining technique, we evaluated whether NIM811 (1, 10, 100 or 1000 ,m) inhibited mPT in the neurons exposed to 100 ,m glutamate. Results Both delayed neuronal injury and apoptosis in the hippocampal CA1 sectors were significantly ameliorated at 72 h after transient forebrain ischaemia in the mice treated with 100 mg/kg NIM811 or 50 mg/kg ciclosporin. The treatments with 100 ,m and 1000 ,m NIM811 significantly inhibited the reduction of mitochondrial membrane potential in the neurons exposed to 100 ,m glutamate. Conclusions These findings strongly suggest that NIM811 inhibits mPT and ameliorates delayed neuronal death in mice subjected to transient forebrain ischaemia. [source]


Siberian ginseng reduces infarct volume in transient focal cerebral ischaemia in Sprague-Dawley rats

PHYTOTHERAPY RESEARCH, Issue 2 2005
Yungmin Bu
Abstract Siberian ginseng, the root and stem bark of Acanthopanax senticosus Harms, has been used as a tonic and adaptogen to strengthen qi in traditional Korean medicine. The neuroprotective effects of water extracts of A. senticosus (ASW) were investigated in transient middle cerebral artery occlusion (MCAo, 90 min occlusion, 24 h reperfusion) of Sprague-Dawley rats. The infarct volume was significantly reduced by 36.6% after the peritoneal injection of ASW (100 mg[sol ]kg) compared with the control. In the immunohistochemical study, ASW markedly inhibited both cyclooxygenase-2 and OX-42 expressions in the penumbral region at 24 h after MCAo. These results suggest that A. senticosus has a neuroprotective effect by inhibiting inflammation and microglial activation in brain ischaemia. Copyright © 2005 John Wiley & Sons, Ltd. [source]


MODULATION OF SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STAT) FACTOR PATHWAYS DURING FOCAL CEREBRAL ISCHAEMIA: A GENE EXPRESSION ARRAY STUDY IN RAT HIPPOCAMPUS AFTER MIDDLE CEREBRAL ARTERY OCCLUSION

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2007
Sheng-Li Sun
SUMMARY 1Signal transducers and activators of transcription (STAT) factors are a family of transcription factors that mediate intracellular signalling initiated at cytokine cell surface receptors and transmitted to the nucleus. In the present study, we determined the global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion using microarray analysis. 2The present study used middle cerebral artery occlusion (MCAO) to induce ischaemia and reperfusion in Sprague-Dawley rats. Using superarray Q series Janus tyrosine kinases (Jak)/STAT signalling pathway gene array, a total of 96 genes was screened in adult male rat hippocampus after transient focal cerebral ischaemia. 3The results showed that 23 genes were upregulated at least twofold by ischaemia treatment and that 12 genes were downregulated at least threefold by ischaemia treatment compared with controls. 4After confirmation by quantitative real-time polymerase chain reaction, the data suggest that the gene expression of STAT2, 5a, 5b, 6 and suppressor of cytokine signalling (SOCS) 4 was increased by ischaemia, probably due to a compensatory response of the brain, which may play a protective role in damaged brain tissue. 5The results of the present study provide evidence on global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion, in which STAT2, 5a, 5b, 6 and SOCS4 were confirmed to be significantly modulated during focal cerebral ischaemia. [source]