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.