Wang Yingpeng, Hameed Mustafa Q, Rakhade Sanjay N, Iglesias Antonio H, Muller Paul A, Mou Dan-Lei, Rotenberg Alexander
Departments of aNeurology bNeurosurgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts cDepartment of Neurology, University of Chicago, Chicago, Illinois, USA dDepartment of Neurology, Beijing Aerospace General Hospital eCenter for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.
Neuroreport. 2014 Aug 20;25(12):954-9. doi: 10.1097/WNR.0000000000000219.
Traumatic brain injury (TBI) is one of the leading causes of neurological disability and death in the USA across all age groups, ethnicities, and incomes. In addition to the short-term morbidity and mortality, TBI leads to epilepsy and severe neurocognitive symptoms, both of which are referenced to post-traumatic hippocampal dysfunction, although the mechanisms of such hippocampal dysfunction are incompletely understood. Here, we study the temporal profile of the transcription of three select immediate early gene (IEG) markers of neuronal hyperactivation, plasticity, and injury, c-fos, brain-derived neurotrophic factor (BDNF), and Bax, in the acute period following the epileptogenic lateral fluid percussion injury in a rodent TBI model. We found that lateral fluid percussion injury leads to enhanced expression of the selected IEGs within 24 h of TBI. Specifically, BDNF and c-fos increase maximally 1-6 h after TBI in the ipsilesional hippocampus, whereas Bax increases in the hippocampus bilaterally in this time window. Antagonism of the N-methyl-D-aspartate-type glutamate receptor by MK801 attenuates the increase in BDNF and Bax, which underscores a therapeutic role for N-methyl-D-aspartate-type glutamate receptor antagonism in the acute post-traumatic time period and suggests a value to a hippocampal IEG readout as an outcome after injury or acute therapeutic intervention.
创伤性脑损伤（TBI）是美国所有年龄组、种族和收入群体中神经功能障碍和死亡的主要原因之一。除了短期的发病率和死亡率外，TBI还会导致癫痫和严重的神经认知症状，这两种情况都与创伤后海马功能障碍有关，尽管这种海马功能障碍的机制尚不完全清楚。在此，我们研究了在啮齿动物TBI模型中，致痫性侧脑液压冲击伤急性期，三种选定的神经元过度激活、可塑性和损伤的即时早期基因（IEG）标志物——c-fos、脑源性神经营养因子（BDNF）和Bax——转录的时间特征。我们发现，侧脑液压冲击伤导致TBI后24小时内选定的IEG表达增强。具体而言，BDNF和c-fos在TBI后1-6小时在同侧海马中最大程度增加，而在此时间窗口内Bax在双侧海马中增加。MK801对N-甲基-D-天冬氨酸型谷氨酸受体的拮抗作用减弱了BDNF和Bax的增加，这突出了N-甲基-D-天冬氨酸型谷氨酸受体拮抗作用在创伤后急性期的治疗作用，并表明海马IEG读数作为损伤或急性治疗干预后结果的价值。
