Center for Neuroscience and Regenerative Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland.
Department of Anatomy, Physiology and Genetics, Uniformed Services University of Health Sciences, Bethesda, Maryland.
J Neurosci Res. 2018 Apr;96(4):556-572. doi: 10.1002/jnr.24218. Epub 2018 Jan 23.
White matter damage is an important consequence of traumatic brain injury (TBI) in humans. Unlike rodents, ferrets have a substantial amount of white matter and a gyrencephalic brain; therefore, they may represent an ideal small mammal model to study human-pertinent consequences of TBI. Here we report immunohistochemical and behavioral results after a controlled cortical impact (CCI) injury to the sensorimotor cortex of adult male ferrets. We assessed inflammation in the neocortex and white matter, and behavior at 1 day post injury and 1, 4, and 16 weeks post injury (WPI). CCI in the ferret produced inflammation that originated in the neocortex near the site of the injury and progressed deep into the white matter with time. The density of microglia and astrocytes increased in the neocortex near the injury, peaking at 4WPI and remaining elevated at 16WPI. Microglial morphology in the neocortex was significantly altered in the first 4 weeks, but showed a return toward normal at 16 weeks. Clusters of microglial cells in the white matter persisted until 16WPI. We assessed motor and cognitive behavior using the open field, novel object recognition, T-maze, and gait tests. A transient deficit in memory occurred at 4WPI, with a reduction of rearing and motor ability at 12 and 16WPI. Behavioral impairments coincide with features of the inflammatory changes in the neocortex revealed by immunohistochemistry. The ferret represents an important animal model to explore ongoing damage in the white matter and cerebral cortex after TBI.
脑白质损伤是人类创伤性脑损伤（TBI）的重要后果。与啮齿动物不同，雪貂有大量的白质和脑回，因此，它们可能是研究人类 TBI 相关后果的理想小型哺乳动物模型。在这里，我们报告了成年雄性雪貂感觉运动皮层受到控制性皮质撞击（CCI）损伤后的免疫组织化学和行为结果。我们评估了损伤后 1 天、1、4 和 16 周（WPI）时新皮层和白质中的炎症以及行为。雪貂的 CCI 产生了炎症，炎症起源于损伤部位附近的新皮层，并随着时间的推移深入白质。小胶质细胞和星形胶质细胞在损伤附近的新皮层中的密度增加，在 4WPI 时达到峰值，并在 16WPI 时仍保持升高。新皮层中小胶质细胞的形态在最初的 4 周内发生了显著改变，但在 16 周时恢复正常。白质中微胶质细胞簇一直持续到 16WPI。我们使用旷场、新物体识别、T 迷宫和步态测试评估运动和认知行为。在 4WPI 时出现记忆短暂缺陷，在 12 和 16WPI 时出现后肢站立和运动能力下降。行为损伤与免疫组织化学显示的新皮层炎症变化特征相吻合。雪貂是一种重要的动物模型，可用于探索 TBI 后白质和大脑皮层的持续损伤。
