Black Elise K, Phillips Jack K, Seminetta Jack, Bailes Julian, Lee John M, Finan John D
Department of Neurosurgery, NorthShore University HealthSystem, Evanston, IL, United States of America.
Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Evanston, IL, United States of America.
Transl Neurosci. 2021 Feb 4;12(1):76-82. doi: 10.1515/tnsci-2021-0010. eCollection 2021 Jan 1.
This study investigated dietary supplementation as a prophylactic for neuroinflammation following traumatic brain injury (TBI) in a preclinical model. Adult male Sprague-Dawley rats received 30 days of supplementation with either water or two dietary supplements. The first consisted of high-dose omega-3 fatty acid (O3FA) (supplement A) along with vitamin D3 and vitamin E. The second had the same ingredients at different doses with an addition of cannabidiol (supplement B). Rats were subjected to an impact TBI and then euthanized 7 days post-injury and neuroinflammation quantified by histological detection of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, and CD68, a marker of microglial activity. There was a trend toward increased GFAP staining in injured, unsupplemented animals as compared to sham, unsupplemented animals, consistent with increased activation of astrocytes in response to trauma which was reversed by supplement A but not by supplement B. The pattern of CD68 staining across groups was similar to that of GFAP staining. There was a trend toward an increase in the injured unsupplemented group, relative to sham which was reversed by supplement A but not by supplement B. CD68 staining in injured animals was concentrated in the perivascular domain. The consistency between trends across different measures of neuroinflammation showing benefits of high-dose O3FA supplementation following TBI suggests that the observed effects are real. These findings are preliminary, but they justify further study to determine the functional benefits associated with improvements in histological outcomes and understand associated dose-response curves.
本研究在临床前模型中探究了膳食补充剂对创伤性脑损伤（TBI）后神经炎症的预防作用。成年雄性Sprague-Dawley大鼠接受了30天的水或两种膳食补充剂的补充。第一种补充剂由高剂量的ω-3脂肪酸（O3FA）（补充剂A）以及维生素D3和维生素E组成。第二种补充剂含有相同成分但剂量不同，并添加了大麻二酚（补充剂B）。大鼠遭受撞击性脑损伤，然后在损伤后7天实施安乐死，并通过组织学检测胶质纤维酸性蛋白（GFAP，星形胶质细胞激活的标志物）和CD68（小胶质细胞活性的标志物）对神经炎症进行量化。与未补充且假手术的动物相比，未补充的受伤动物中GFAP染色有增加的趋势，这与创伤后星形胶质细胞激活增加一致，补充剂A可逆转这种情况，但补充剂B不能。各组间CD68染色模式与GFAP染色相似。相对于假手术组，未补充的受伤组有增加的趋势，补充剂A可逆转这种情况，但补充剂B不能。受伤动物中的CD68染色集中在血管周围区域。不同神经炎症测量指标的趋势之间的一致性表明，TBI后高剂量O3FA补充具有益处，这表明观察到的效果是真实的。这些发现是初步的，但它们为进一步研究提供了依据，以确定与组织学结果改善相关的功能益处，并了解相关的剂量反应曲线。
