Goddeyne Corey, Nichols Joshua, Wu Chen, Anderson Trent
University of Arizona, College of Medicine-Phoenix, Phoenix, Arizona; and School of Life Sciences, Arizona State University, Tempe, Arizona.
University of Arizona, College of Medicine-Phoenix, Phoenix, Arizona; and.
J Neurophysiol. 2015 May 1;113(9):3268-80. doi: 10.1152/jn.00970.2014. Epub 2015 Feb 18.
Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for nearly 75% of all TBI cases, yet its neuropathophysiology is still poorly understood. While even a single mTBI injury can lead to persistent deficits, repeat injuries increase the severity and duration of both acute symptoms and long-term deficits. In this study, to model pediatric repetitive mTBI (rmTBI) we subjected unrestrained juvenile animals (postnatal day 20) to repeat weight-drop impacts. Animals were anesthetized and subjected to sham injury or rmTBI once per day for 5 days. Magnetic resonance imaging (MRI) performed 14 days after injury revealed marked cortical atrophy and ventriculomegaly in rmTBI animals. Specifically, beneath the impact zone the thickness of the cortex was reduced by up to 46% and the area of the ventricles increased by up to 970%. Immunostaining with the neuron-specific marker NeuN revealed an overall loss of neurons within the motor cortex but no change in neuronal density. Examination of intrinsic and synaptic properties of layer II/III pyramidal neurons revealed no significant difference between sham-injured and rmTBI animals at rest or under convulsant challenge with the potassium channel blocker 4-aminopyridine. Overall, our findings indicate that the neuropathological changes reported after pediatric rmTBI can be effectively modeled by repeat weight drop in juvenile animals. Developing a better understanding of how rmTBI alters the pediatric brain may help improve patient care and direct "return to game" decision making in adolescents.
创伤性脑损伤（TBI）最常发生于儿科患者，仍然是儿童死亡和残疾的主要原因。轻度创伤性脑损伤（mTBI）占所有TBI病例的近75%，但其神经病理生理学仍知之甚少。即使单次mTBI损伤也可导致持续性缺陷，而重复性损伤会增加急性症状和长期缺陷的严重程度及持续时间。在本研究中，为模拟儿科重复性轻度创伤性脑损伤（rmTBI），我们对未受约束的幼年动物（出生后第20天）施加重复性重物坠落撞击。动物麻醉后，每天接受一次假损伤或rmTBI，持续5天。损伤后14天进行的磁共振成像（MRI）显示，rmTBI动物出现明显的皮质萎缩和脑室扩大。具体而言，在撞击区域下方，皮质厚度减少多达46%，脑室面积增加多达970%。用神经元特异性标志物NeuN进行免疫染色显示，运动皮质内神经元总体减少，但神经元密度无变化。对II/III层锥体神经元的内在特性和突触特性进行检查发现，在静息状态下或用钾通道阻滞剂4-氨基吡啶进行惊厥激发时，假损伤动物和rmTBI动物之间无显著差异。总体而言，我们的研究结果表明，儿科rmTBI后报告的神经病理学变化可通过幼年动物重复性重物坠落有效模拟。更好地了解rmTBI如何改变儿科大脑，可能有助于改善患者护理，并指导青少年“重返比赛”的决策。
