Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Neurotrauma, Neurodegeneration, and Restoration, Corporal Michael J. Crescenz VA Medical Center, 19104, USA.
Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Neurotrauma, Neurodegeneration, and Restoration, Corporal Michael J. Crescenz VA Medical Center, 19104, USA.
Exp Neurol. 2021 Jun;340:113649. doi: 10.1016/j.expneurol.2021.113649. Epub 2021 Feb 15.
Traumatic brain injury (TBI) can produce physical disruptions in the plasma membranes of neurons, referred to as mechanoporation, which lead to increased cell permeability. We suspect that such trauma-induced membrane disruptions may be influenced by the physical properties of the plasma membrane, such as elasticity or rigidity. These membrane properties are influenced by lipid composition, which can be modulated via diet, leading to the intriguing possibility of prophylactically altering diet to confer resiliency to this mechanism of acute neuronal damage in TBI. In this proof-of-concept study, we used three different diets-one high in polyunsaturated fatty acids suggested to increase elasticity (Fish Oil), one high in saturated fatty acids and cholesterol suggested to increase rigidity (High Fat), and one standard rat chow (Control)-to alter brain plasma membrane lipid composition before subjecting rats to lateral fluid percussion injury (FPI). Lipid analysis (n = 12 rats) confirmed that diets altered brain fatty acid composition after 4 weeks of feeding, with the Fish Oil diet increasing unsaturated fatty acids, and interestingly, the High Fat diet increasing omega-6 docosapentaenoic acid. One cohort of animals (n = 34 rats) was assessed immediately after FPI or sham injury for acute changes in neuronal membrane permeability in the injury-adjacent cortex. Surprisingly, sham animals fed Fish Oil had increased membrane permeability, suggesting altered passive membrane properties. In contrast, injured animals fed the High Fat diet displayed less intense uptake of permeability marker, suggesting a reduced extent of injury-induced plasma membrane disruption, although the density of affected cells matched the other diet groups. In a separate cohort survived for 7 days after FPI (n = 48 rats), animals fed the High Fat diet exhibited a reduced lesion area. At both time points there were no statistically significant differences in inflammation. Unexpectedly, these results indicate that the High Fat diet, as opposed to the Fish Oil diet, beneficially modulated acute plasma membrane permeability and resulted in a smaller lesion size at 7 days post-injury. Additional studies are necessary to determine the impact of these various diets on behavioral outcomes post-TBI. Further investigation is also needed to understand the physical properties in neuronal plasma membranes that may underlie increased resiliency to trauma-induced disruptions and, importantly, to understand how these properties may be influenced by targeted dietary modifications for vulnerable populations.
创伤性脑损伤（TBI）会导致神经元的质膜产生物理破坏，称为机械穿孔，从而导致细胞通透性增加。我们推测，这种创伤引起的膜破坏可能受到质膜物理性质的影响，例如弹性或刚性。这些膜特性受脂质组成的影响，而脂质组成可以通过饮食来调节，从而产生了一种有趣的可能性，即通过预防性改变饮食来改变这种 TBI 中急性神经元损伤的机制的弹性。在这项概念验证研究中，我们使用了三种不同的饮食方式——一种富含多不饱和脂肪酸以增加弹性（鱼油），一种富含饱和脂肪酸和胆固醇以增加刚性（高脂肪），以及一种标准的大鼠饲料（对照）——在使大鼠遭受侧方液压冲击伤（FPI）之前改变大脑质膜的脂质组成。脂质分析（n=12 只大鼠）证实，饮食改变了大脑脂肪酸组成，经过 4 周的喂养后，鱼油饮食增加了不饱和脂肪酸，有趣的是，高脂肪饮食增加了 ω-6 二十二碳五烯酸。一组动物（n=34 只大鼠）在 FPI 或假损伤后立即评估，以评估损伤相邻皮质中神经元质膜通透性的急性变化。令人惊讶的是，接受鱼油饮食的假损伤动物的膜通透性增加，表明被动膜特性发生改变。相比之下，接受高脂肪饮食的受伤动物对通透性标记物的摄取较少，表明损伤诱导的质膜破坏程度降低，尽管受影响细胞的密度与其他饮食组匹配。在另一个接受 FPI 后存活 7 天的队列中（n=48 只大鼠），接受高脂肪饮食的动物的损伤面积减小。在这两个时间点，炎症均无统计学差异。出乎意料的是，这些结果表明，与鱼油饮食相比，高脂肪饮食有益地调节了急性质膜通透性，并导致伤后 7 天的损伤面积减小。还需要进一步的研究来确定这些不同的饮食对 TBI 后行为结果的影响。还需要进一步研究以了解神经元质膜中的物理特性，这些特性可能是增加对创伤引起的破坏的弹性的基础，重要的是，要了解这些特性如何通过针对脆弱人群的靶向饮食改变来影响。
