Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia

作者：Li Yonggang; Xu Zhenfeng; Ford Gregory D^*; Croslan DaJoie R; Cairobe Tariq; Li Zhenzhong; Ford Byron D

来源：Brain Research, 2007, 1184: 277-283.

DOI：10.1016/j.brainres.2007.09.037

• apoptosis
• acetylcholine receptor
• inducing activity (ARIA)
• ErbB, excitotoxicity
• glial growth factor (GGF)
• heregulin
• inflammation
• ischemia
• Neu differentiation factor (NDF)
• stroke

Neuregulin-1 (NRG-1) is a growth factor with potent neuroprotective capacity in ischemic stroke. We recently showed that NRG-1 reduced neuronal death following transient middle cerebral artery occlusion (tMCAO) by up to 90% with an extended therapeutic Here, we examined the neuroprotective potential of NRG-1 using a permanent MCAO ischemia (pMCAO) rat model. NRG-1 reduced infarction in pMCAO by 50% when administered prior to ischemia. We previously demonstrated using gene expression profiling that pMCAO was associated with an exaggerated excitotoxicity response compared to tMCAO. Therefore, we examined whether co-treatment with an inhibitor of excitotoxicity would augment the effect of NRG-1 following pMCAO. Both NRG-1 and the N-methyl-D-aspartate (NMDA) antagonist MK-801 similarly reduced infarct size following pMCAO. However, combination treatment with both NRG-1 and MK-801 resulted in greater neuroprotection than either compound alone, including a 75% reduction in cortical infarction compared to control. Consistent with these findings, NRG-1 reduced neuronal death using an in vitro ischemia model and this effect was augmented by MK-801. These results demonstrate the efficacy of NRG-1 in pMCAO rat focal ischemia model. Our findings further indicate the potential clinically relevance of NRG-1 alone or as a combination strategy for treating ischemic stroke.

• 出版日期2007-12-12
• 单位山东大学