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.
Xu
Zhenfeng
Z
Department of Anatomy and Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Jiang
Ju
J
Ford
Gregory
G
Ford
Byron D
BD
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