Wang Silun, Li Yonggang, Paudyal Ramesh, Ford Byron D, Zhang Xiaodong
Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
J Neurol Sci. 2015 Oct 15;357(1-2):28-34. doi: 10.1016/j.jns.2015.06.055. Epub 2015 Jun 27.
The neuroprotective effects of neuregulin-1 (NRG-1) on stroke lesions were assessed longitudinally in rats with middle cerebral artery occlusion (MCAo) using MRI. Sprague-Dawley rats (n=16, 250±20g) underwent permanent MCAo surgery with cerebral blood flow (CBF) monitored by laser doppler flowmetry at ipsilateral side of bregma for 20min post-occlusion. A single 50μl bolus dose of NRG-1 or vehicle was administered into the left internal carotid artery immediately prior to MCAo. The expansion of the ischemic lesion into the cortex was attenuated by NRG-1 over a 48-hour (h) time span as measured by diffusion weighted imaging (DWI). The final infarct volumes of NRG-1 treated rats were significantly smaller than those of the vehicle treated rats at 48h (264.8±192.1 vs. 533.4±175.5mm(3), p<0.05). The NRG-1 treated rats were further subdivided into 2 subgroups according to their CBF reduction during stroke surgery: mild ischemia (<70% CBF reduction) or severe ischemia (>70% CBF reduction). In particular, ischemic infarction was not usually observed in the cortex of NRG-1 treated rats with mild ischemia at 3 and 48h post-occlusion. Histological results validated the imaging findings and demonstrated that NRG-1 treated rats had fewer injured neurons in peri-infarct areas 48h post-ischemia. In summary, the neuroprotective effect of NRG-1 in the pMCAo stroke model was demonstrated by prevention of ischemic lesion expansion, reduced infarct volume and protection of neurons from ischemic damage.
使用磁共振成像（MRI）对大脑中动脉闭塞（MCAo）大鼠的神经损伤进行纵向评估，以研究神经调节蛋白-1（NRG-1）对中风损伤的神经保护作用。将16只体重250±20g的Sprague-Dawley大鼠进行永久性MCAo手术，闭塞后20分钟通过激光多普勒血流仪监测同侧前囟处的脑血流量（CBF）。在MCAo之前，立即经左颈内动脉给予50μl单剂量的NRG-1或赋形剂。通过扩散加权成像（DWI）测量，在48小时的时间跨度内，NRG-1减轻了缺血性病变向皮质的扩展。在48小时时，NRG-1治疗组大鼠的最终梗死体积显著小于赋形剂治疗组大鼠（264.8±192.1 vs. 533.4±175.5mm³，p<0.05）。根据中风手术期间CBF降低的程度，将NRG-1治疗组大鼠进一步分为2个亚组：轻度缺血（CBF降低<70%）或重度缺血（CBF降低>70%）。特别是，在闭塞后3小时和48小时，轻度缺血的NRG-1治疗组大鼠的皮质中通常未观察到缺血性梗死。组织学结果证实了影像学发现，并表明在缺血后48小时，NRG-1治疗组大鼠梗死周围区域的受损神经元较少。总之，在pMCAo中风模型中，NRG-1的神经保护作用表现为预防缺血性病变扩展、减少梗死体积以及保护神经元免受缺血损伤。
