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Higher n-3 Polyunsaturated Fatty Acid Diet Improves Long-Term Neuropathological and Functional Outcome after Repeated Mild Traumatic Brain Injury
Journal of Neurotrauma ( IF 3.9 ) Pub Date : 2021-08-23 , DOI: 10.1089/neu.2021.0096
Abhishek Desai 1 , Huazhen Chen 1, 2 , Karl Kevala 1 , Hee-Yong Kim 1, 2
Affiliation  

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.

中文翻译:


较高的 n-3 多不饱和脂肪酸饮食可改善反复轻度脑外伤后的长期神经病理学和功能结果



反复轻度创伤性脑损伤(TBI)可引起持续的神经病理学影响,是慢性创伤性脑病的主要危险因素。在大多数情况下,PUFA(n-3 多不饱和脂肪酸)被证明可以改善单次损伤模型中的急性 TBI 结局。在这项研究中,我们使用工程旋转加速闭头冲击模型 (CHIMERA) 证明了膳食 n-3 PUFA 对反复轻度 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。以n-3 PUFA充足(较高n-3 PUFA)或缺乏(较低n-3 PUFA)饮食饲养的成年小鼠,连续3天每天给予温和的CHIMERA。受伤后2个月,评估视觉功能和空间记忆。使用离子钙结合接头分子 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的活化,并使用银染色检查轴突损伤。与缺乏饮食的组相比,喂食 n-3 PUFA 充足饮食的小鼠的视神经束、胼胝体和海马中重复嵌合体 (rCHIMERA) 诱导的神经胶质增生受到显着抑制。 rCHIMERA后在视束中检测到相当大的轴突损伤,但与缺乏饮食组相比,充足饮食组显示出较少的轴突损伤。 rCHIMERA 导致两个饮食组中视觉诱发电位的 N1 波幅以及缺乏饮食组中视网膜电图的 a 波波幅急剧下降。然而,在适当饮食组中,N1 和 a 波振幅的降低不太严重。莫里斯水迷宫探针测试表明,与充足饮食组相比,缺乏饮食组的平台穿越次数显着减少。 总之,膳食 n-3 PUFA 可以减轻持续的神经胶质细胞活化和轴突损伤,并改善反复轻度 TBI 后的视觉功能和空间记忆缺陷。这些数据支持较高 n-3 PUFA 饮食在改善反复轻度 TBI 不良后果方面具有神经保护潜力。
更新日期:2021-09-20
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