Prefrontal Ischemia in the Rat Leads to Secondary Damage and Inflammation in Remote Gray and White Matter Regions.
Prefrontal Ischemia in the Rat Leads to Secondary Damage and Inflammation in Remote Gray and White Matter Regions.
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DOI：
10.3389/fnins.2016.00081
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发表时间：
2016
影响因子：
4.3
通讯作者：
Whitehead SN
中科院分区：
文献类型：
--
作者：
Weishaupt N;Zhang A;Deziel RA;Tasker RA;Whitehead SN
继发性损伤过程，如炎症和氧化应激，可加重缺血性病变并扩散到邻近的脑区。然而，很少有研究调查远离梗死的区域如何在中风后也会发生变性和炎症。为了了解中风后远距离脑区受到影响的程度，我们使用了双侧内皮素-1诱导的前额叶梗死大鼠模型。卒中后28天，使用FluoroJadeB（FJB）分析前额皮质梗死后的脑区域是否存在持续的神经变性，并使用Iba 1和OX-6免疫组织化学分析神经炎症。FJB阳性的丘脑背内侧核（DMN）和压后区（RSA）的皮质显示大量的神经炎症。仅在皮质内观察到显著的神经元损失。FJB阳性内囊中显著的小胶质细胞募集和激活表明远处白色物质病理学。这些发现表明，即使是远离梗死的区域也会根据解剖学连接性受到可预测的影响，并且白色物质炎症是远程病理学的组成部分。这种病理学的延迟性质使其成为预防性治疗的有效靶点，可能具有使用抗炎剂进行治疗干预的延长的时间窗。
Secondary damage processes, such as inflammation and oxidative stress, can exacerbate an ischemic lesion and spread to adjacent brain regions. Yet, few studies investigate how regions remote from the infarct could also suffer from degeneration and inflammation in the aftermath of a stroke. To find out to what extent far-remote brain regions are affected after stroke, we used a bilateral endothelin-1-induced prefrontal infarct rat model. Brain regions posterior to the prefrontal cortical infarct were analyzed for ongoing neurodegeneration using FluoroJadeB (FJB) and for neuroinflammation using Iba1 and OX-6 immunohistochemistry 28 days post-stroke. The FJB-positive dorsomedial nucleus of the thalamus (DMN) and retrosplenial area (RSA) of the cortex displayed substantial neuroinflammation. Significant neuronal loss was only observed within the cortex. Significant microglia recruitment and activation in the FJB-positive internal capsule indicates remote white matter pathology. These findings demonstrate that even regions far remote from an infarct are affected predictably based on anatomical connectivity, and that white matter inflammation is an integral part of remote pathology. The delayed nature of this pathology makes it a valid target for preventative treatment, potentially with an extended time window of opportunity for therapeutic intervention using anti-inflammatory agents.