Diverse changes in microglia morphology and axonal pathology during the course of 1 year after mild traumatic brain injury in pigs.
Diverse changes in microglia morphology and axonal pathology during the course of 1 year after mild traumatic brain injury in pigs.
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DOI：
10.1111/bpa.12953
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Duda JE
中科院分区：
文献类型：
--
作者：
Grovola MR;Paleologos N;Brown DP;Tran N;Wofford KL;Harris JP;Browne KD;Shewokis PA;Wolf JA;Cullen DK;Duda JE
在美国，每年有超过280万人经历轻度创伤性脑损伤(TBI)，这可能会导致长期的神经功能障碍。由颅脑损伤引起的机械力通过大脑传播，产生弥漫性轴索损伤(DAI)，并触发继发性神经炎性级联反应。这种级联反应可能会在受伤后的急性到慢性时间点持续，改变大脑的内稳态。然而，弥漫性脑损伤的标志性轴突病理与胶质细胞激活或形态的潜在变化之间的关系尚未在慢性时间点的临床相关大型动物模型中建立。在这项研究中，我们评估了头部在冠状平面快速旋转的猪的组织，以产生轻微的脑外伤。对损伤后1年的标本进行轴突病理、小胶质细胞形态变化和星形胶质细胞反应性的神经病理学评估。我们检测到在单次轻度脑损伤后，整体淀粉样前体蛋白病理以及脑室周围白质和海马伞/穹隆病理增加。我们没有检测到胼胝体完整性或星形胶质细胞反应性的变化。然而，详细的小胶质细胞骨骼分析显示形态发生了变化，最显著的是小胶质细胞分支、连接和终点数的增加。这些细微的变化在脑室周围白质和某些海马区最为明显，在某些情况下可观察到损伤后1年。这些持续的形态变化表明神经免疫稳态的持续变化。需要更多的研究来确定潜在的分子和神经生理学改变，以及对神经缺陷的潜在贡献。在这项研究中，猪通过快速头部旋转造成轻度脑创伤，并在伤后一年内对轴突病理、小胶质细胞形态变化和星形胶质细胞反应进行了神经病理学评估。我们检测到轴突病理的急性变化，特别是在脑室周围白质和海马伞/穹隆，以及损伤后一年脑室周围白质和海马亚区的小胶质细胞形态的变化。这些持续的形态变化表明，单次轻度脑损伤后，神经免疫稳态持续改变。
Over 2.8 million people experience mild traumatic brain injury (TBI) in the United States each year, which may lead to long‐term neurological dysfunction. The mechanical forces that are caused by TBI propagate through the brain to produce diffuse axonal injury (DAI) and trigger secondary neuroinflammatory cascades. The cascades may persist from acute to chronic time points after injury, altering the homeostasis of the brain. However, the relationship between the hallmark axonal pathology of diffuse TBI and potential changes in glial cell activation or morphology have not been established in a clinically relevant large animal model at chronic time points. In this study, we assessed the tissue from pigs subjected to rapid head rotation in the coronal plane to generate mild TBI. Neuropathological assessments for axonal pathology, microglial morphological changes, and astrocyte reactivity were conducted in specimens out to 1‐year post‐injury. We detected an increase in overall amyloid precursor protein pathology, as well as periventricular white matter and fimbria/fornix pathology after a single mild TBI. We did not detect the changes in corpus callosum integrity or astrocyte reactivity. However, detailed microglial skeletal analysis revealed changes in morphology, most notably increases in the number of microglial branches, junctions, and endpoints. These subtle changes were most evident in periventricular white matter and certain hippocampal subfields, and were observed out to 1‐year post‐injury in some cases. These ongoing morphological alterations suggest persistent change in neuroimmune homeostasis. Additional studies are needed to characterize the underlying molecular and neurophysiological alterations, as well as potential contributions to neurological deficits. In this study, pigs were subjected to mild TBI by rapid head rotation and neuropathologically assessed for axonal pathology, microglial morphological changes, and astrocyte reactivity out to one year post injury. We detected acute changes in axonal pathology, particularly in the periventricular white matter and fimbria/fornix, as well as changes to microglia morphology in the periventricular white matter and hippocampal subfields out to one year post injury. These ongoing morphological alterations suggest persistent changes in neuroimmune homeostasis after a single mild TBI.
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影响因子：
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