Department of Physiology, Loma Linda University, Loma Linda, California, USA.
J Neurotrauma. 2012 Jul 20;29(11):2060-74. doi: 10.1089/neu.2011.1883.
Traumatic brain injury (TBI) affects many infants and children, and results in enduring motor and cognitive impairments with accompanying changes in white matter tracts, yet few experimental studies in rodent juvenile models of TBI (jTBI) have examined the timeline and nature of these deficits, histologically and functionally. We used a single controlled cortical impact (CCI) injury to the parietal cortex of rats at post-natal day (P) 17 to evaluate behavioral alterations, injury volume, and morphological and molecular changes in gray and white matter, with accompanying measures of electrophysiological function. At 60 days post-injury (dpi), we found that jTBI animals displayed behavioral deficits in foot-fault and rotarod tests, along with a left turn bias throughout their early developmental stages and into adulthood. In addition, anxiety-like behaviors on the zero maze emerged in jTBI animals at 60 dpi. The final lesion constituted only ∼3% of brain volume, and morphological tissue changes were evaluated using MRI, as well as immunohistochemistry for neuronal nuclei (NeuN), myelin basic protein (MBP), neurofilament-200 (NF200), and oligodendrocytes (CNPase). White matter morphological changes were associated with a global increase in MBP immunostaining and reduced compound action potential amplitudes at 60 dpi. These results suggest that brain injury early in life can induce long-term white matter dysfunction, occurring in parallel with the delayed development and persistence of behavioral deficits, thus modeling clinical and longitudinal TBI observations.
创伤性脑损伤（TBI）影响许多婴儿和儿童，并导致持久的运动和认知障碍，同时伴有白质束的变化，但在幼年创伤性脑损伤（jTBI）的啮齿动物模型中，很少有实验研究从组织学和功能上检查这些缺陷的时间进程和性质。我们使用单一的皮质撞击（CCI）损伤，在出生后第 17 天（P）损伤大鼠顶叶皮层，以评估行为改变、损伤体积、灰质和白质的形态和分子变化，并进行电生理功能的伴随测量。在损伤后 60 天（dpi），我们发现 jTBI 动物在足失误和旋转棒测试中表现出行为缺陷，同时在整个早期发育阶段和成年期表现出左偏。此外，jTBI 动物在零迷宫上出现了类似焦虑的行为。最终的损伤仅占大脑体积的约 3%，并使用 MRI 以及神经元核（NeuN）、髓鞘碱性蛋白（MBP）、神经丝-200（NF200）和少突胶质细胞（CNPase）的免疫组织化学评估组织形态变化。白质形态变化与 MBP 免疫染色的整体增加以及 60 dpi 时复合动作电位幅度降低有关。这些结果表明，生命早期的脑损伤可导致长期的白质功能障碍，与行为缺陷的延迟发育和持续存在平行发生，从而模拟临床和纵向 TBI 的观察结果。
