Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
Neurosci Lett. 2022 Feb 6;771:136430. doi: 10.1016/j.neulet.2021.136430. Epub 2021 Dec 29.
Clinical observations indicate that body weight (BW) extremes are associated with worse outcome after traumatic brain injury (TBI); yet, it is uncertain whether the baseline BW (bBW) may affect outcome after mouse TBI. We retrospectively analyzed 129 similarly aged (9-12 weeks) male C57BL6/J mice that were subjected to repetitive closed head TBI (rTBI) using an established weight drop paradigm as well as 55 sham injured mice. We sought to determine whether the bBW as well as the post-TBI weight relative to baseline (%BW) were associated with a variety of post-rTBI outcomes, including acute model complications (skull fractures and macroscopic hemorrhage), impact seizures, return of the righting reflex (RR), the neurological severity score (NSS), post-rTBI BW-change, and 28-day mortality. In a subset of rTBI mice, we also assessed for potential associations between the bBW and %BW and performance in the novel object recognition (NOR) task and various histological outcomes at 28 days. We found no association between the bBW with acute model complications, impact seizure burden, RR, NSS, and NOR performance at 28 days, as well as cerebral microbleed burden, presence of hyperphosphorylated tau, and TDP-43 pathology after rTBI. However, a higher bBW was associated with a longer time to first impact seizure, a greater microglial activation, astrocytosis, and neuronal loss in the injured cerebral cortex at 28 days. A greater %BW-loss was associated with a shorter impact seizure-free survival, longer time to return of the righting reflex, greater neurological deficit severity as assessed by the NSS and NOR, and worse mortality. On multiple linear regression there was no independent association of the %BW-loss with neuronal loss and neuroinflammation after adjustment for the bBW. These observations indicate that the bBW and %BW-loss may be important biological variables in certain experimental mouse TBI investigations, depending on the outcome measures of interest.
临床观察表明，体重（BW）极端与创伤性脑损伤（TBI）后预后较差有关；然而，尚不清楚基线 BW（bBW）是否会影响小鼠 TBI 后的预后。我们回顾性分析了 129 只年龄相似（9-12 周）的雄性 C57BL6/J 小鼠，它们使用既定的重物坠落范式接受了重复闭合性颅脑损伤（rTBI），以及 55 只假损伤小鼠。我们试图确定 bBW 以及相对于基线的 post-TBI 体重（%BW）是否与各种 post-rTBI 结果相关，包括急性模型并发症（颅骨骨折和宏观出血）、冲击性癫痫发作、翻正反射（RR）恢复、神经严重程度评分（NSS）、post-rTBI BW 变化和 28 天死亡率。在 rTBI 小鼠的亚组中，我们还评估了 bBW 和 %BW 与新物体识别（NOR）任务中的表现之间的潜在关联以及 28 天后的各种组织学结果。我们发现 bBW 与急性模型并发症、冲击性癫痫发作负担、RR、NSS 和 28 天时的 NOR 表现以及 rTBI 后的脑微出血负担、过度磷酸化 tau 的存在和 TDP-43 病理学之间没有关联。然而，较高的 bBW 与首次冲击性癫痫发作的时间较长、受伤大脑皮层中的小胶质细胞激活、星形胶质细胞增生和神经元丢失较多有关。较大的 %BW 损失与无冲击性癫痫发作的生存时间较短、RR 恢复时间较长、NSS 和 NOR 评估的神经功能缺损严重程度较大以及死亡率较高有关。在多元线性回归中，在校正 bBW 后，%BW 损失与神经元丢失和神经炎症之间没有独立关联。这些观察结果表明，bBW 和 %BW 损失可能是某些实验性小鼠 TBI 研究中重要的生物学变量，这取决于感兴趣的结果测量。
