Laboratory of Molecular Signaling, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Center for Neuroscience and Regenerative Medicine, Henry M. Jackson Foundation, Bethesda, Maryland, USA.
J Neurotrauma. 2021 Sep 15;38(18):2622-2632. doi: 10.1089/neu.2021.0096. Epub 2021 Jul 20.
Repeated mild traumatic brain injury (TBI) can cause persistent neuropathological effects and is a major risk factor for chronic traumatic encephalopathy. PUFAs (n-3 polyunsaturated fatty acids) were shown to improve acute TBI outcomes in single-injury models in most cases. In this study, we demonstrate positive effects of dietary n-3 PUFA on long-term neuropathological and functional outcome in a clinically relevant model of repeated mild TBI using the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA). Adult mice, reared on n-3 PUFA adequate (higher n-3 PUFA) or deficient (lower n-3 PUFA) diets, were given a mild CHIMERA daily for 3 consecutive days. At 2 months after injury, visual function and spatial memory were evaluated. Glia cell activation was assessed by immunostaining using antibodies of ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein, and axonal damage was examined using silver staining. Repeated CHIMERA (rCHIMERA)-induced gliosis was significantly suppressed in the optic tract, corpus callosum, and hippocampus of mice fed the n-3 PUFA adequate diet compared to the deficient diet group. Considerable axonal damage was detected in the optic tract after rCHIMERA, but the adequate diet group displayed less axonal damage compared to the deficient diet group. rCHIMERA induced a drastic reduction in N1 amplitude of the visual evoked potential in both diet groups and the a-wave amplitude of the electroretinogram in the deficient diet group. However, reduction of N1 and a-wave amplitude were less severe in the adequate diet group. The Morris water maze probe test indicated a significant decrease in the number of platform crossings in the deficient diet group compared to the adequate group. In summary, dietary n-3 PUFA can attenuate persistent glial cell activation and axonal damage and improve deficits in visual function and spatial memory after repeated mild TBI. These data support the neuroprotective potential of a higher n-3 PUFA diet in ameliorating the adverse outcome of repeated mild TBI.
反复轻度创伤性脑损伤（TBI）可导致持续性神经病理学效应，是慢性创伤性脑病的主要危险因素。多不饱和脂肪酸（n-3 多不饱和脂肪酸）在大多数情况下显示出改善单次损伤模型中急性 TBI 结果的作用。在这项研究中，我们使用闭合性头部撞击工程旋转加速度模型（CHIMERA）展示了饮食中 n-3 多不饱和脂肪酸对重复性轻度 TBI 临床相关模型中长期神经病理学和功能结果的积极影响。成年小鼠在 n-3 多不饱和脂肪酸充足（较高的 n-3 多不饱和脂肪酸）或不足（较低的 n-3 多不饱和脂肪酸）饮食中饲养，连续 3 天每天给予轻度 CHIMERA。在受伤后 2 个月，评估视觉功能和空间记忆。使用离子钙结合衔接蛋白 1 和神经胶质纤维酸性蛋白的抗体通过免疫染色评估神经胶质细胞激活，并通过银染色检查轴突损伤。与缺乏饮食组相比，在 n-3 多不饱和脂肪酸充足饮食组的视神经、胼胝体和海马体中，重复 CHIMERA（rCHIMERA）诱导的神经胶质增生明显受到抑制。rCHIMERA 后在视神经中检测到相当大的轴突损伤，但充足饮食组的轴突损伤比缺乏饮食组少。rCHIMERA 导致两个饮食组的视觉诱发电位 N1 振幅急剧降低，并且缺乏饮食组的视网膜电图 a 波振幅降低。然而，在充足饮食组中，N1 和 a 波振幅的降低不那么严重。 Morris 水迷宫探测试验表明，缺乏饮食组与充足饮食组相比，穿越平台的次数明显减少。总之，饮食中 n-3 多不饱和脂肪酸可减轻重复性轻度 TBI 后的持续性神经胶质细胞激活和轴突损伤，并改善视觉功能和空间记忆缺陷。这些数据支持更高 n-3 多不饱和脂肪酸饮食在改善重复性轻度 TBI 不良后果方面的神经保护潜力。
