Assessment of behavioral, neuroinflammatory, and histological responses in a model of rat repetitive mild fluid percussion injury at 2 weeks post-injury.
Assessment of behavioral, neuroinflammatory, and histological responses in a model of rat repetitive mild fluid percussion injury at 2 weeks post-injury.
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DOI：
10.3389/fneur.2022.945735
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发表时间：
2022
影响因子：
3.4
通讯作者：
Carlson, Shaun W.
中科院分区：
文献类型：
--
作者：
Fronczak, Katherine M.;Roberts, Andrea;Svirsky, Sarah;Parry, Madison;Holets, Erik;Henchir, Jeremy;Dixon, C. Edward;Carlson, Shaun W.
关键词：
重复性轻度创伤性脑损伤（rmTBI）是一个突出的公共卫生问题，与慢性后遗症有关。开发可靠和良好表征的rmTBI临床前模型对于研究潜在的病理生理机制至关重要，因为模型可能具有不同的参数，影响所产生的损伤的整体病理学。侧向液压冲击损伤（FPI）模型是啮齿动物受试者中TBI复制的可靠且常用的方法，尽管其目前在rmTBI研究中相对未被充分利用。在这项研究中，我们进行了一个新的描述的变化的横向重复轻度FPI（rmFPI）模型，显示分级急性行为障碍和组织病理学发生在响应一个，两个或四个轻度FPI（1.25大气压）或假手术，实施24小时间隔。横梁行走性能显示受伤动物的运动功能明显受损，功能障碍随着额外的损伤而增加。基于行为反应和组织学观察，我们进一步研究了双重FPI（dFPI）的亚急性病理生理结果。免疫反应性评估表明，dFPI导致区域特异性减少突触后蛋白神经颗粒素和增加皮质下白色物质染色的突触前蛋白突触素在2周后dFPI。小胶质细胞标记物Iba-1的免疫组织化学评估显示在几个脑区中显著增加，星形胶质细胞标记物GFAP的评估显示在皮质下白色物质和丘脑中的免疫反应性显著增加。通过这项研究，我们提供了一个新的帐户的亚急性损伤后的结果发生在响应rmFPI利用这些损伤和频率参数，从而也证明了横向FPI模型在rmTBI复制的可靠性。
Repetitive mild traumatic brain injury (rmTBI) is a prominent public health concern, with linkage to debilitating chronic sequelae. Developing reliable and well-characterized preclinical models of rmTBI is imperative in the investigation of the underlying pathophysiological mechanisms, as models can have varying parameters, affecting the overall pathology of the resulting injury. The lateral fluid percussion injury (FPI) model is a reliable and frequently used method of TBI replication in rodent subjects, though it is currently relatively underutilized in rmTBI research. In this study, we have performed a novel description of a variation of the lateral repetitive mild FPI (rmFPI) model, showing the graded acute behavioral impairment and histopathology occurring in response to one, two or four mild FPI (1.25 atm) or sham surgeries, implemented 24h apart. Beam walking performance revealed significant motor impairment in injured animals, with dysfunction increasing with additional injury. Based upon behavioral responses and histological observations, we further investigated the subacute pathophysiological outcomes of the dual FPI (dFPI). Immunoreactivity assessments showed that dFPI led to regionally-specific reductions in the post-synaptic protein neurogranin and increased subcortical white matter staining of the presynaptic protein synaptophysin at 2 weeks following dFPI. Immunohistochemical assessments of the microglial marker Iba-1 showed a striking increase in in several brain regions, and assessment of the astrocytic marker GFAP showed significantly increased immunoreactivity in the subcortical white matter and thalamus. With this study, we have provided a novel account of the subacute post injury outcomes occurring in response to a rmFPI utilizing these injury and frequency parameters, and thereby also demonstrating the reliability of the lateral FPI model in rmTBI replication.
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DOI：
10.1097/nen.0000000000000115
发表时间：
2014-10
影响因子：
3.2
作者：
Bolton AN;Saatman KE
通讯作者：
Saatman KE
影响因子：
2.5
作者：
Bennett RE;Mac Donald CL;Brody DL
通讯作者：
Brody DL
影响因子：
11.4
作者：
EDELMANN, L;HANSON, PI;JAHN, R
通讯作者：
JAHN, R
影响因子：
3.4
作者：
Carlson SW;Henchir J;Dixon CE
通讯作者：
Dixon CE
影响因子：
4.1
作者：
DIXON, CE;LYETH, BG;HAYES, RL
通讯作者：
HAYES, RL