Department of Physiology, Loma Linda University, Loma Linda, CA 92354, USA.
Neuroscience. 2012 Oct 11;222:366-78. doi: 10.1016/j.neuroscience.2012.06.033. Epub 2012 Jun 21.
Traumatic brain injury (TBI) is one of the leading causes of death and disability in children and adolescents. The neuropathological sequelae that result from TBI are a complex cascade of events including edema formation, which occurs more frequently in the pediatric than the adult population. This developmental difference in the response to injury may be related to higher water content in the young brain and also to molecular mechanisms regulating water homeostasis. Aquaporins (AQPs) provide a unique opportunity to examine the mechanisms underlying water mobility, which remain poorly understood in the juvenile post-traumatic edema process. We examined the spatiotemporal expression pattern of principal brain AQPs (AQP1, AQP4, and AQP9) after juvenile TBI (jTBI) related to edema formation and resolution observed using magnetic resonance imaging (MRI). Using a controlled cortical impact in post-natal 17 day-old rats as a model of jTBI, neuroimaging analysis showed a global decrease in water mobility (apparent diffusion coefficient, ADC) and an increase in edema (T2-values) at 1 day post-injury, which normalized by 3 days. Immunohistochemical analysis of AQP4 in perivascular astrocyte endfeet was increased in the lesion at 3 and 7days post-injury as edema resolved. In contrast, AQP1 levels distant from the injury site were increased at 7, 30, and 60 days within septal neurons but did not correlate with changes in edema formation. Group differences were not observed for AQP9. Overall, our observations confirm that astrocyticAQP4 plays a more central role than AQP1 or AQP9 during the edema process in the young brain.
创伤性脑损伤（TBI）是儿童和青少年死亡和残疾的主要原因之一。TBI 引起的神经病理学后果是一系列复杂的事件，包括水肿形成，在儿科人群中比成人更常见。这种对损伤反应的发育差异可能与年轻大脑中含水量较高有关，也可能与调节水稳态的分子机制有关。水通道蛋白（AQP）为研究水流动性的机制提供了一个独特的机会，而这些机制在青少年创伤后水肿过程中仍知之甚少。我们研究了主要脑 AQP（AQP1、AQP4 和 AQP9）在与使用磁共振成像（MRI）观察到的水肿形成和消退相关的幼年创伤性脑损伤（jTBI）后的时空表达模式。使用出生后 17 天大的大鼠的皮质撞击作为 jTBI 的模型，神经影像学分析显示水流动性（表观扩散系数，ADC）在损伤后 1 天整体下降，水肿（T2 值）增加，在 3 天内恢复正常。损伤后 3 天和 7 天，血管周围星形胶质细胞足突中的 AQP4 在病变中增加，水肿消退。相比之下，在损伤部位远处的 AQP1 水平在 7、30 和 60 天内的隔神经元中升高，但与水肿形成的变化无关。AQP9 没有观察到组间差异。总的来说，我们的观察结果证实，在年轻大脑的水肿过程中，星形胶质细胞 AQP4 比 AQP1 或 AQP9 发挥更核心的作用。
