Department of Neurology, University of Mississippi Medical Center, Jackson, MS 39216, United States of America.
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70116, United States of America.
Exp Neurol. 2024 Sep;379:114888. doi: 10.1016/j.expneurol.2024.114888. Epub 2024 Jul 14.
Traumatic brain injury (TBI) is one of the most common causes of emergency room visits in children, and it is a leading cause of death in juveniles in the United States. Similarly, a high proportion of this population consumes diets that are high in saturated fats, and millions of children are overweight or obese. The goal of the present study was to assess the relationship between diet and TBI on cognitive and cerebrovascular outcomes in juvenile rats. In the current study, groups of juvenile male Long Evans rats were subjected to either mild TBI via the Closed-Head Injury Model of Engineered Rotational Acceleration (CHIMERA) or underwent sham procedures. The animals were provided with either a combination of high-fat diet and a mixture of high-fructose corn syrup (HFD/HFCS) or a standard chow diet (CH) for 9 days prior to injury. Prior to injury, the animals were trained on the Morris water maze for three consecutive days, and they underwent a post-injury trial on the day of the injury. Immediately after TBI, the animals' righting reflexes were tested. Four days post-injury, the animals were euthanized, and brain samples and blood plasma were collected for qRT-PCR, immunohistochemistry, and triglyceride assays. Additional subsets of animals were used to investigate cerebrovascular perfusion using Laser Speckle and perform immunohistochemistry for endothelial cell marker RECA. Following TBI, the righting reflex was significantly increased in TBI rats, irrespective of diet. The TBI worsened the rats' performance in the post-injury trial of the water maze at 3 h, p(injury) < 0.05, but not at 4 days post-injury. Reduced cerebrovascular blood flow using Laser Speckle was demonstrated in the cerebellum, p(injury) < 0.05, but not foci of the cerebral cortices or superior sagittal sinus. Immunoreactive staining for RECA in the cortex and corpus callosum was significantly reduced in HFD/HFCS TBI rats, p < 0.05. qRT-PCR showed significant increases in APOE, CREB1, FCGR2B, IL1B, and IL6, particularly in the hippocampus. The results from this study offer robust evidence that HFD/HFCS negatively influences TBI outcomes with respect to cognition and cerebrovascular perfusion of relevant brain regions in the juvenile rat.
创伤性脑损伤 (TBI) 是儿童急诊最常见的原因之一，也是美国青少年死亡的主要原因。同样，这部分人群中有很大比例的人饮食中饱和脂肪含量高，数以百万计的儿童超重或肥胖。本研究的目的是评估饮食与 TBI 对幼年大鼠认知和脑血管结果的关系。在本研究中，将一组幼年雄性 Long Evans 大鼠通过闭合性头部损伤工程旋转加速模型 (CHIMERA) 或假手术使其发生轻度 TBI。动物在受伤前 9 天接受高脂肪饮食和高果糖玉米糖浆混合物 (HFD/HFCS) 或标准饲料 (CH) 的组合喂养。在受伤前，动物在 Morris 水迷宫上连续训练 3 天，并在受伤当天进行受伤后试验。TBI 后立即测试动物的翻正反射。受伤后 4 天，处死动物，采集脑样本和血浆进行 qRT-PCR、免疫组织化学和甘油三酯测定。另外一部分动物用于使用激光散斑研究脑血管灌注，并进行内皮细胞标志物 RECA 的免疫组织化学。TBI 后，无论饮食如何，TBI 大鼠的翻正反射明显增加。TBI 使大鼠在水迷宫受伤后试验中的表现恶化，在 3 小时时 p(injury) < 0.05，但在 4 天受伤后时没有。激光散斑显示小脑的脑血管血流减少，p(injury) < 0.05，但大脑皮质或上矢状窦的焦点没有。HFD/HFCS TBI 大鼠皮质和胼胝体的 RECA 免疫反应性染色明显减少，p < 0.05。qRT-PCR 显示 APOE、CREB1、FCGR2B、IL1B 和 IL6 显著增加，尤其是在海马体中。本研究的结果提供了有力的证据，表明 HFD/HFCS 对幼年大鼠的 TBI 结果产生负面影响，特别是在认知和相关脑区的脑血管灌注方面。
