Zaini A, Morgan P K, Cardwell B, Vlassopoulos E, Sgro M, Li C N, Salberg S, Mellett N A, Christensen J, Meikle P J, Murphy A J, Marsland B J, Mychasiuk R, Yamakawa G R
Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia; Gastroenterology, Immunology, and Neuroscience Discovery Program, Monash University, Melbourne, Victoria, Australia.
Haematopoiesis and Leukocyte Biology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Diabetes, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Exp Neurol. 2025 Mar;385:115108. doi: 10.1016/j.expneurol.2024.115108. Epub 2024 Dec 9.
Mild traumatic brain injury (mTBI) research has had limited success translating treatments from preclinical models to clinical application for concussion. One major factor that has been overlooked is the near 24-hour availability of food, both for experimental nocturnal rodents and patients suffering from mTBI. Here, we characterised the impact of food restriction limited to either the inactive (day) or the active phase (night), on repetitive mTBI (RmTBI) - induced outcomes in male and female rats. We found that active phase fed rats consumed more food, had increased body weight, and reduced brain weights. Behaviourally, active phase feeding increased motor coordination deficits and caused changes to thermal nociceptive processing following RmTBI. Hypothalamic transcriptomic analysis revealed minor changes in response to RmTBI, and genes associated with oxytocin-vasopressin regulation in response to inactive phase, but not active phase feeding. These transcript changes were absent in females, where the overall effect of RmTBI was minor. Prefrontal cortex lipidomics revealed an increase in sphingomyelin synthesis following injury and marked sex differences in response to feeding. Of the lipids that changed and overlapped between the prefrontal cortex and serum, dihydroceramides, sphingomyelins, and hexosylceramides, were higher in the serum but lower in the prefrontal cortex. Together, these results demonstrate that feeding time alters outcomes to RmTBI, independent of the hypothalamic transcriptome, and injury-specific lipids may serve as useful biomarkers in RmTBI diagnosis.
轻度创伤性脑损伤（mTBI）的研究在将临床前模型中的治疗方法转化为脑震荡的临床应用方面取得的成功有限。一个被忽视的主要因素是食物几乎24小时供应，这对于实验性夜行性啮齿动物和患有mTBI的患者来说都是如此。在这里，我们描述了仅限于非活动期（白天）或活动期（夜间）的食物限制对雄性和雌性大鼠重复性mTBI（RmTBI）诱导的结果的影响。我们发现，活动期喂食的大鼠消耗更多食物，体重增加，脑重量减轻。在行为方面，活动期喂食增加了运动协调缺陷，并在RmTBI后引起热痛觉处理的变化。下丘脑转录组分析显示，对RmTBI的反应有微小变化，以及与非活动期而非活动期喂食时催产素-加压素调节相关的基因。这些转录变化在雌性中不存在，在雌性中RmTBI的总体影响较小。前额叶皮质脂质组学显示，损伤后鞘磷脂合成增加，并且在对喂食的反应中存在明显的性别差异。在前额叶皮质和血清中发生变化且重叠的脂质中，二氢神经酰胺、鞘磷脂和己糖神经酰胺在血清中较高，但在前额叶皮质中较低。总之，这些结果表明，喂食时间会改变RmTBI的结果，独立于下丘脑转录组，并且损伤特异性脂质可能作为RmTBI诊断中的有用生物标志物。
