Neuroprotective effects of neuregulin-1 in rat models of focal cerebral ischemia.
The purpose of this study was to investigate the therapeutic efficacy and mechanism of recombinant human NRG-1 to attenuate ischemia/reperfusion brain injury. NRG-1(3.0 ng/kg) was applied intravascularly 10 min before middle cerebral artery occlusion (MCAO) and then focal cerebral ischemia for 90 min and reperfusion for 24 h. The rats were scored post-reperfusion for neurological deficits and infarct volume in the brain was assessed by 2,3,5-triphenyltetrazolium chloride(TTC). Apoptosis was evaluated by TUNEL staining. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure changes of caspase-3 mRNA. The level of TNF-alpha was determined using enzyme-linked immunosorbent assay (ELISA). Our results demonstrated that recombinant human NRG-1 could reduce cerebral infarct volume by about 71% (P < 0.05) and TUNEL positive cells when given immediately before MCAO, and improved behavior of animals. Furthermore, we also showed that NRG-1 could also decrease the expression of caspase-3 mRNA and production of TNF-alpha protein. These data suggest that pre-administration of NRG-1 attenuates cerebral ischemia and reperfusion injury. This protective effect may be involved in the inhibition of caspase-3 and TNF-alpha.
Guo
Wen-Ping
WP
Department of Anatomy, Shanghai Medical College, Fudan University, 138 YiXue Yuan Road, Shanghai 200032, PR China. gyowenping68@163.com
Wang
Jie
J
Li
Rui-Xi
RX
Peng
Yu-Wen
YW
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002544:Cerebral Infarction / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D020890:Neuregulin-1 / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D015424:Reperfusion / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013778:Tetrazolium Salts; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020890:Neuregulin-1; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D013778:Tetrazolium Salts; D014409:Tumor Necrosis Factor-alpha; C009591:triphenyltetrazolium; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases