title: siRNA-mediated silence of protease-activated receptor-1 minimizes ischemic injury of cerebral cortex through HSP70 and MAP2.
abstract: Cerebral ischemic stroke is a prevalent disease in senior individuals. The anticoagulation and thrombolysis to recover blood supply as well as the diminution of neural excitotoxicity to protect brain cells have not shown to fully improve stroke patients. The comprehensive mechanisms and medication specificity remain to be addressed. The silence of specific mRNAs by RNA interference provides revenues for such goals. We examined whether the silence of protease-activated receptor-1 (PAR-1) by siRNA protects brain tissues from ischemic injury. In three groups of Wistar rats, their lateral ventricles received the injections of lentiviral vectors carrying siRNA for PAR1, small RNA in mismatching PAR1 or saline. A week after the injections, these rats were treated by one side of middle cerebral artery occlusion (MCAO). The scores of neurological deficits, the volume of ischemic infarction and the expressions of PAR-1, HSP-70 and MAP-2 were measured in 24h of MCAO. Our results show that the silence of PAR-1 significantly reduces neurological deficits and infarction volume, as well as elevates HSP-70 and MAP-2 expressions. Thus, the knock-down of PAR1 minimizes the ischemic impairments of cerebral cortex via HSP70 and MAP-2 pathways.
authors: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China.
authors: Jun
authors: J
authors: Zhang
authors: Ying
authors: Y
authors: Wang
authors: Ping
authors: P
authors: Zhu
authors: Xudong
authors: X
authors: Wang
authors: Manhua
authors: M
authors: Lv
authors: Honglin
authors: H
authors: Feng
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000627:therapeutic use; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007276:Injections, Intraventricular; D016086:Lentivirus / Q000235:genetics; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D034622:RNA Interference / Q000187:drug effects; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors
chemical_list: D018840:HSP70 Heat-Shock Proteins; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; D010975:Platelet Aggregation Inhibitors