Persistence of Hyper-Ramified Microglia in Porcine Cortical Gray Matter after Mild Traumatic Brain Injury.
Persistence of Hyper-Ramified Microglia in Porcine Cortical Gray Matter after Mild Traumatic Brain Injury.
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DOI：
10.3390/biomedicines11071960
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发表时间：
2023-07-12
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
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创伤性脑损伤 (TBI) 是美国发病率和死亡率的主要原因，每年有数百万人因暴露于 TBI 而去急诊室就诊。不幸的是，对于轻度 TBI（TBI 最常见的严重亚型）的病理学尚未达成共识。先前的临床前和尸检人类研究详细说明了 TBI 后弥漫性轴突损伤的存在，表明白质病理学是弥漫性脑损伤的主要病理学。然而，TBI 产生的惯性载荷会在灰质和白质中产生应变场。为了进一步表征轻度 TBI 中的灰质病理学特征，我们的实验室使用闭头旋转加速诱导 TBI 的猪模型 (n = 25) 来评估受伤后 1 年内大脑皮层的血脑屏障破坏、神经变性、星形胶质细胞增生和小胶质细胞反应性。免疫组织化学染色显示，扣带回损伤后 30 天到损伤后 1 年（p < 0.05）以及颞下回急性和亚急性时间点（p < 0.05）存在超分支小胶质细胞表型，即更多分支、连接点、终点和更长的总突长度。有趣的是，我们没有发现神经元丢失或星形胶质细胞反应性与这些慢性小胶质细胞变化相伴。然而，我们观察到纤维蛋白原反应性（血脑屏障破坏的衡量标准）在 3 DPI 时主要出现在灰质中（p = 0.0003），在 7 DPI 到慢性时间点时解析为假水平。未来的研究应该采用基因表达测定、神经影像学和行为测定来阐明这些超分支小胶质细胞的影响，特别是与神经可塑性和对潜在后续损伤的反应有关。进一步了解轻度 TBI 后大脑的炎症活动将有望提供对病理生理学的理解，从而转化为 TBI 的临床治疗。
Traumatic brain injury (TBI) is a major contributor to morbidity and mortality in the United States as several million people visit the emergency department every year due to TBI exposures. Unfortunately, there is still no consensus on the pathology underlying mild TBI, the most common severity sub-type of TBI. Previous preclinical and post-mortem human studies have detailed the presence of diffuse axonal injury following TBI, suggesting that white matter pathology is the predominant pathology of diffuse brain injury. However, the inertial loading produced by TBI results in strain fields in both gray and white matter. In order to further characterize gray matter pathology in mild TBI, our lab used a pig model (n = 25) of closed-head rotational acceleration-induced TBI to evaluate blood-brain barrier disruptions, neurodegeneration, astrogliosis, and microglial reactivity in the cerebral cortex out to 1 year post-injury. Immunohistochemical staining revealed the presence of a hyper-ramified microglial phenotype—more branches, junctions, endpoints, and longer summed process length—at 30 days post injury (DPI) out to 1 year post injury in the cingulate gyrus (p < 0.05), and at acute and subacute timepoints in the inferior temporal gyrus (p < 0.05). Interestingly, we did not find neuronal loss or astroglial reactivity paired with these chronic microglia changes. However, we observed an increase in fibrinogen reactivity—a measure of blood-brain barrier disruption—predominately in the gray matter at 3 DPI (p = 0.0003) which resolved to sham levels by 7 DPI out to chronic timepoints. Future studies should employ gene expression assays, neuroimaging, and behavioral assays to elucidate the effects of these hyper-ramified microglia, particularly related to neuroplasticity and responses to potential subsequent insults. Further understanding of the brain’s inflammatory activity after mild TBI will hopefully provide understanding of pathophysiology that translates to clinical treatment for TBI.
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