Madathil Sindhu K, Deng-Bryant Ying, Wilfred Bernard S, Leung Lai Yee, Gilsdorf Janice S, Shear Deborah A
Brain Trauma Neuroprotection and Neurorestoration Branch (S.K.M., Y.D., B.S.W., L.Y.L., J.S.G., D.A.S.), Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland.
J Trauma Acute Care Surg. 2017 Jul;83(1 Suppl 1):S16-S24. doi: 10.1097/TA.0000000000001471.
Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) are essential for neuroplasticity and neuronal survival. Despite the importance of these endogenous factors in mediating posttraumatic recovery, little is known about their response after penetrating type traumatic brain injury. The objective of this study was to quantify the expression levels BDNF and IGF-1, two well-known neuroplasticity mediators, after penetrating ballistic-like brain injury (PBBI).
Rats were randomly assigned to receive unilateral sham or PBBI injuries. Using enzyme-linked immunosorbent assay and immunohistochemistry, we performed a comprehensive evaluation of BDNF and IGF-1 expression at acute (1 hour, 6 hours, 1 day) and subacute (2, 3, 7, and 14 days) timepoints after injury.
BDNF and IGF-1 expression was transiently upregulated in both cortex and hippocampus after PBBI. Although BDNF levels increased at acute timepoints, IGF-1 expression peaked at 3 days in cortical homogenates. Although there was loss of staining in cells bordering the cavity, increased BDNF and IGF-1 immunoreactivity was observed in scattered neurons away from the contusion site. Glial upregulation of both growth factors was observed at early timepoints in the hippocampus.
Our findings demonstrate that PBBI results in a brief upregulation of BDNF and IGF-1 during early posttraumatic period, providing critical information for interventions aiming to enhance neuronal survival and brain plasticity.
脑源性神经营养因子(BDNF)和胰岛素样生长因子-1(IGF-1)对神经可塑性和神经元存活至关重要。尽管这些内源性因子在介导创伤后恢复中很重要,但对于穿透性创伤性脑损伤后它们的反应知之甚少。本研究的目的是量化穿透性弹道样脑损伤(PBBI)后两种著名的神经可塑性介质BDNF和IGF-1的表达水平。
将大鼠随机分为接受单侧假手术或PBBI损伤。使用酶联免疫吸附测定和免疫组织化学,我们在损伤后的急性(1小时、6小时、1天)和亚急性(2、3、7和14天)时间点对BDNF和IGF-1表达进行了全面评估。
PBBI后,皮质和海马中的BDNF和IGF-1表达均短暂上调。虽然BDNF水平在急性时间点升高,但IGF-1表达在皮质匀浆中于第3天达到峰值。尽管在空洞周围的细胞中染色缺失,但在远离挫伤部位的散在神经元中观察到BDNF和IGF-1免疫反应性增加。在海马的早期时间点观察到两种生长因子的胶质细胞上调。
我们的研究结果表明,PBBI导致创伤后早期BDNF和IGF-1短暂上调,为旨在提高神经元存活和脑可塑性的干预措施提供了关键信息。