Neuregulin-1 is neuroprotective and attenuates inflammatory responses induced by ischemic stroke.
Recent work from our laboratory demonstrated that the expression neuregulin-1 in neurons was induced in the ischemic penumbra by focal stroke in the rat. Here, we show that a single intravascular injection of neuregulin-1beta (approximately 2.5 ng/kg) reduced cortical infarct volume by >98% when given immediately before middle cereral artery occlusion. Subcortical infarct volume was reduced by approximately 40%. Analysis of DNA fragmentation in brain tissues indicated that neuregulin-1 blocked apoptosis in cortical neurons in the penumbra. Neuregulin-1 prevented macrophage/microglial infiltration and astrocytic activation following focal ischemia. The neuroprotective effect of neuregulin-1 was also associated with a suppression of interleukin-1beta mRNA levels. These data suggest that neuregulin-1 protects neurons from delayed, ischemia-induced apoptotic cell death in the cortex by inhibiting pro-inflammatory responses. Neuregulins represent a novel, potent neuroprotective strategy that has potential therapeutic value in treating individuals after acute ischemic stroke.
Department of Anatomy and Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Zhenfeng
Z
Xu
Ju
J
Jiang
Gregory
G
Ford
Byron D
BD
Ford
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D020890:Neuregulin-1 / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
D007375:Interleukin-1; D020890:Neuregulin-1; D012333:RNA, Messenger