Laboratory of Molecular Biology, Research and Development 151, Bay Pines VA Healthcare System, Bay Pines, FL 33744, USA.
Brain Res. 2011 Nov 24;1425:123-31. doi: 10.1016/j.brainres.2011.09.047. Epub 2011 Sep 29.
Repetitive mild traumatic brain injury (mTBI) represents a major public health problem. Many individuals who suffer repetitive mTBIs suffer from Post-Concussion Syndrome, a constellation of neuropsychiatric symptoms that includes depression, anxiety, and problems with memory and other cognitive processes. Significantly, Post-Concussion Syndrome is resistant to existing therapeutic strategies. To provide better treatment options for this patient population, the underlying pathophysiology of repetitive mTBI must be understood. A first step in this process is the establishment of an in vitro model system that recapitulates the biological changes that occur in the brains of repetitively injured humans. The availability of a model with immortalized cell lines would remove the considerable barriers of time, expense, and difficulties with genetic manipulation that exist with the use of primary neuronal cultures. Here we report the development and functional characterization of an in vitro laboratory model of repetitive TBI using immortalized neuronal cell lines. These results indicate that the moderate, repetitive injury reduces viability, numbers and lengths of neurites, and that the neuronal loss mechanism includes caspase activation.
重复性轻度创伤性脑损伤（mTBI）是一个主要的公共卫生问题。许多遭受重复性 mTBI 的人患有脑震荡后综合征，这是一组神经精神症状，包括抑郁、焦虑以及记忆和其他认知过程的问题。值得注意的是，脑震荡后综合征对现有的治疗策略具有抗性。为了为这一患者群体提供更好的治疗选择，必须了解重复性 mTBI 的潜在病理生理学。这一过程的第一步是建立一个体外模型系统，该系统可重现反复受伤的人类大脑中发生的生物学变化。具有永生化细胞系的模型的可用性将消除使用原代神经元培养物所存在的时间、费用和遗传操作困难等重大障碍。在这里，我们报告了使用永生化神经元细胞系建立重复性 TBI 的体外实验室模型的开发和功能特征。这些结果表明，中度、重复性损伤会降低细胞活力、轴突数量和长度，并且神经元丧失机制包括半胱天冬酶激活。
