Fasting is neuroprotective following traumatic brain injury
Fasting is neuroprotective following traumatic brain injury
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DOI：
10.1002/jnr.21628
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发表时间：
2008-06-01
影响因子：
4.2
通讯作者：
Sullivan, Patrick G.
中科院分区：
文献类型：
--
作者：
Davis, Laurie M.;Pauly, James R.;Sullivan, Patrick G.
为了确定禁食对创伤性脑损伤(TBI)后的神经保护作用并阐明其可能的机制，我们采用可控性皮质撞击(CCI)损伤模型，对成年雄性SD大鼠造成中度或重度损伤。组织保护评估用于确定禁食、低血糖(胰岛素10U)或酮(1.66mmoles/kg/d或0.83mmoles/kg/day；D-β-羟丁酸酯)给药的神经保护水平。线粒体分离和呼吸研究用于确定损伤部位线粒体的功能。我们还研究了氧化应激的生物标志物，如脂质/蛋白质氧化、活性氧(ROS)产生和线粒体内钙负荷，作为线粒体动态平衡的次要指标。我们发现，禁食24小时，而不是48小时，在中度(1.5 mm)但不严重(2.0 mm)CCI后，组织节省显著增加。这一24小时的禁食还降低了氧化应激和钙负荷的生物标志物，并增加了从损伤部位分离的线粒体的氧化磷酸化。胰岛素注射旨在模拟禁食时的降糖效果，但在中度CCI损伤后并未导致显著的组织保留，事实上在某些注射时间点导致死亡率增加。然而，在中度损伤后，使用酮导致组织节约性增加。中度(1.5 mm)颅脑损伤后禁食24小时可提供神经保护、维持认知功能和改善线粒体功能。潜在的机制似乎与酮症有关，而不是低血糖。(C)2008年Wiley-Liss，Inc.
To determine the neuroprotective effect of fasting after traumatic brain injury (TBI) and to elucidate the potential underlying mechanisms, we used a controlled cortical impact (CCI) injury model to induce either a moderate or a severe injury to adult male Sprague Dawley rats. Tissue-sparing assessments were used to determine the level of neuroprotection of fasting, hypoglycemia (insulin 10 U), or ketone (1.66 mmoles/kg/day or 0.83 mmoles/kg/day; D-beta-hydroxtbutyrate) administration. Mitochondrial isolation and respiratory studies were utilized to determine the functionality of mitochondria at the site of injury. We also investigated biomarkers of oxidative stress, such as lipid/protein oxidation, reactive oxygen species (ROS) production, and intramitochondrial calcium load, as a secondary measure of mitochondrial homeostasis. We found that fasting animals for 24 hr, but not 48 hr, after a moderate (1.5 mm), but not severe (2.0 mm), CCI resulted in a significant increase in tissue sparing. This 24-hr fast also decreased biomarkers of oxidative stress and calcium loading and increased mitochondrial oxidative phosphorylation in mitochondria isolated from the site of injury. Insulin administration, designed to mimic the hypoglycemic effect seen during fasting did not result in significant tissue sparing after moderate CCI injury and in fact induced increased mortality at some injection time points. However, the administration of ketones resulted in increased tissue sparing after moderate injury. Fasting for 24 hr confers neuroprotection, maintains cognitive function, and improves mitochondrial function after moderate (1.5 mm) TBI. The underlying mechanism appears to involve ketosis rather than hypoglycemia. (c) 2008 Wiley-Liss, Inc.