Nguyen Tara, Mao Yilin, Sutherland Theresa, Gorrie Catherine Anne
School of Life Sciences, Faculty of Science, University of Technology Sydney, New South Wales, Australia.
Neural Regen Res. 2017 Nov;12(11):1885-1894. doi: 10.4103/1673-5374.219051.
Traumatic spinal cord injury (SCI) is a detrimental condition that causes loss of sensory and motor function in an individual. Many complex secondary injury cascades occur after SCI and they offer great potential for therapeutic targeting. In this study, we investigated the response of endogenous neural progenitor cells, astrocytes, and microglia to a localized thoracic SCI throughout the neuroaxis. Twenty-five adult female Sprague-Dawley rats underwent mild-contusion thoracic SCI (n = 9), sham surgery (n = 8), or no surgery (n = 8). Spinal cord and brain tissues were fixed and cut at six regions of the neuroaxis. Immunohistochemistry showed increased reactivity of neural progenitor cell marker nestin in the central canal at all levels of the spinal cord. Increased reactivity of astrocyte-specific marker glial fibrillary acidic protein was found only at the lesion epicenter. The number of activated microglia was significantly increased at the lesion site, and activated microglia extended to the lumbar enlargement. Phagocytic microglia and macrophages were significantly increased only at the lesion site. There were no changes in nestin, glial fibrillary acidic protein, microglia and macrophage response in the third ventricle of rats subjected to mild-contusion thoracic SCI compared to the sham surgery or no surgery. These findings indicate that neural progenitor cells, astrocytes and microglia respond differently to a localized SCI, presumably due to differences in inflammatory signaling. These different cellular responses may have implications in the way that neural progenitor cells can be manipulated for neuroregeneration after SCI. This needs to be further investigated.
创伤性脊髓损伤(SCI)是一种有害病症,会导致个体感觉和运动功能丧失。SCI后会发生许多复杂的继发性损伤级联反应,它们为治疗靶点提供了巨大潜力。在本研究中,我们研究了内源性神经祖细胞、星形胶质细胞和小胶质细胞对贯穿神经轴的局限性胸段SCI的反应。25只成年雌性Sprague-Dawley大鼠接受了轻度挫伤性胸段SCI(n = 9)、假手术(n = 8)或未手术(n = 8)。脊髓和脑组织在神经轴的六个区域进行固定和切片。免疫组织化学显示,在脊髓各水平的中央管中,神经祖细胞标志物巢蛋白的反应性增加。仅在损伤中心发现星形胶质细胞特异性标志物胶质纤维酸性蛋白的反应性增加。损伤部位活化小胶质细胞的数量显著增加,且活化的小胶质细胞延伸至腰膨大。吞噬性小胶质细胞和巨噬细胞仅在损伤部位显著增加。与假手术或未手术相比,轻度挫伤性胸段SCI大鼠第三脑室中的巢蛋白、胶质纤维酸性蛋白、小胶质细胞和巨噬细胞反应没有变化。这些发现表明,神经祖细胞、星形胶质细胞和小胶质细胞对局限性SCI的反应不同,可能是由于炎症信号的差异。这些不同的细胞反应可能对SCI后神经祖细胞用于神经再生的操控方式具有影响。这需要进一步研究。