Hoffman S W, Fülöp Z, Stein D G
Brain Research Laboratory, Rutgers University, Newark, New Jersey.
J Neurotrauma. 1994 Aug;11(4):417-31. doi: 10.1089/neu.1994.11.417.
The purpose of this study was to develop a bilateral model of frontal cortical contusion in the rat that would demonstrate reproducible deficits typically found after frontal lobe injury in humans. We used a pneumatically controlled cortical impactor to create bilateral contusions of the medial prefrontal cortex (PFC) in adult male Sprague-Dawley rats. Cognitive, neurologic, physiologic, and histopathologic measures were used to evaluate changes caused by the injury. The cognitive task employed the Morris water maze (MWM). Contused rats performed worse than sham-operated controls on measures of time taken to find a submerged platform, distance to the platform, and swim strategy. Neurologic measures revealed impairments of tongue mobility and transient deficits of forelimb placing. Body weights of the contused rats were chronically reduced with respect to controls, indicating that cortical contusion produces disruption in homeostasis. All rats given bilateral PFC contusions developed marked necrotic cavities at the site of impact. The borders surrounding the cavities were heavily lined with astrocytes and ameboid microglia. There was subcortical gliosis in the medial caudate that extended throughout the rostral-caudal length of the caudate-putamen and into the mediodorsal (MD) and ventrolateral (VL) nuclei of the thalamus. The thalamus was also the site of distal transneuronal degeneration. In both the MD and the VL, there was significant neuronal loss in the contused rats as compared with sham-operated controls. This method of bilateral cortical contusion demonstrates clear, reproducible results that would be required for the development of future pharmacologic therapies designed to promote functional recovery.
本研究的目的是建立一种大鼠双侧额叶皮质挫伤模型，该模型将表现出人类额叶损伤后通常出现的可重复的缺陷。我们使用气动控制的皮质撞击器在成年雄性Sprague-Dawley大鼠中制造内侧前额叶皮质（PFC）的双侧挫伤。采用认知、神经、生理和组织病理学测量方法来评估损伤引起的变化。认知任务采用莫里斯水迷宫（MWM）。在寻找水下平台所需时间、到平台的距离和游泳策略等测量指标上，挫伤大鼠的表现比假手术对照组差。神经学测量显示舌活动能力受损和前肢放置的短暂缺陷。与对照组相比，挫伤大鼠的体重长期减轻，这表明皮质挫伤会破坏体内平衡。所有接受双侧PFC挫伤的大鼠在撞击部位都出现了明显的坏死腔。腔周围的边界处密集排列着星形胶质细胞和阿米巴样小胶质细胞。内侧尾状核存在皮质下胶质增生，其延伸至尾状核-壳核的整个头尾长度，并进入丘脑的内侧背核（MD）和腹外侧核（VL）。丘脑也是远端跨神经元变性的部位。与假手术对照组相比，挫伤大鼠的MD和VL中均有明显的神经元丢失。这种双侧皮质挫伤方法显示出清晰、可重复的结果，这是未来旨在促进功能恢复的药物治疗开发所必需的。
