Lyeth B G, Jenkins L W, Hamm R J, Dixon C E, Phillips L L, Clifton G L, Young H F, Hayes R L
Department of Surgery, Richard Roland Reynolds Neurosurgical Research Laboratories, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
Brain Res. 1990 Sep 3;526(2):249-58. doi: 10.1016/0006-8993(90)91229-a.
Prolonged neurological dysfunction that results from an insult to the brain is often attributed to irreversible structural damage such as loss of neurons or axonal degeneration. For example, following cerebral ischemia even partial hippocampal CA1 neuronal loss has been proposed to be sufficient to result in deficits in hippocampal dependent spatial memory. This study examined if hippocampal CA1 neuronal loss and/or axonal injury was necessary to produce prolonged spatial memory deficits resulting from traumatic brain injury (TBI). Prior to TBI Sprague-Dawley rats were trained on an 8-arm radial maze, a task sensitive to detecting specific lesions of the hippocampus or its extrinsic connections. Following a mild, moderate, or sham injury, rats were tested for working and reference memory for 25 days. After 25 days of maze testing, histological cell counts were made from consistent coronal sections of the mid-dorsal hippocampus. Rats subjected to mild or moderate TBI manifested working memory deficits for 5 and 15 days, respectively, after injury in the absence of overt (all brain regions) or quantitative (CA1 only) evidence of neuronal death. The number of CA1 pyramidal neurons of representative sections of the mid-dorsal hippocampi for injured maze-deficit rats and sham control rats were: 1626 (S.E.M. = +/- 66) and 1693 (S.E.M. = +/- 69) per 10(6) micron2, respectively. Additionally, no overt evidence of axonal injury was observed in any forebrain structure including major intrinsic or extrinsic connecting hippocampal pathways. These data strongly suggest that mild to moderate TBI is capable of producing prolonged spatial memory deficits in the rat without evidence of either neuronal cell death in the intrinsic hippocampus or overt axonal injury in hippocampal pathways.
由脑部损伤导致的长期神经功能障碍通常归因于不可逆的结构损伤，如神经元丢失或轴突退化。例如，在脑缺血后，即使部分海马CA1神经元丢失也被认为足以导致海马依赖的空间记忆缺陷。本研究探讨了海马CA1神经元丢失和/或轴突损伤是否是创伤性脑损伤（TBI）导致长期空间记忆缺陷所必需的。在TBI之前，将Sprague-Dawley大鼠训练在一个8臂放射状迷宫上，该任务对检测海马或其外在连接的特定损伤很敏感。在轻度、中度或假损伤后，对大鼠进行25天的工作记忆和参考记忆测试。在进行25天的迷宫测试后，对中背侧海马的连续冠状切片进行组织学细胞计数。遭受轻度或中度TBI的大鼠在受伤后分别表现出5天和15天的工作记忆缺陷，而此时没有明显（所有脑区）或定量（仅CA1）的神经元死亡证据。受伤且有迷宫缺陷的大鼠和假手术对照大鼠的中背侧海马代表性切片中CA1锥体神经元的数量分别为：每10(6)平方微米1626个（标准误=±66）和1693个（标准误=±69）。此外，在任何前脑结构中，包括主要的内在或外在连接海马通路，均未观察到明显的轴突损伤证据。这些数据强烈表明，轻度至中度TBI能够在大鼠中产生长期的空间记忆缺陷，而没有内在海马神经元细胞死亡或海马通路明显轴突损伤的证据。
