Igarashi Takuji, Potts Matthew B, Noble-Haeusslein Linda J
Department of Neurological Surgery, University of California, San Francisco, 521 Parnassus Avenue, Room C-224, San Francisco, CA 94143-0520, USA.
Exp Neurol. 2007 Jan;203(1):258-68. doi: 10.1016/j.expneurol.2006.08.030. Epub 2006 Oct 12.
Clinical evidence suggests that the cerebellum is damaged after traumatic brain injury (TBI) and experimental studies have validated these observations. We have previously shown cerebellar vulnerability, as demonstrated by Purkinje cell loss and microglial activation, after fluid percussion brain injury. In this study, we examine the effect of graded controlled cortical impact (CCI) injury on the cerebellum in the context of physiologic and anatomical parameters that have been shown by others to be sensitive to injury severity. Adult male rats received mild, moderate, or severe CCI and were euthanized 7 days later. We first validated the severity of the initial injury using physiologic criteria, including apnea and blood pressure, during the immediate postinjury period. Increasing injury severity was associated with an increased incidence of apnea and higher mortality. Severe injury also induced transient hypertension followed by hypotension, while lower grade injuries produced an immediate and sustained hypotension. We next evaluated the pattern of subcortical neuronal loss in response to graded injuries. There was significant neuronal loss in the ipsilateral cortex, hippocampal CA2/CA3, and laterodorsal thalamus that was injury severity-dependent and that paralleled microglial activation. Similarly, there was a distinctive pattern of Purkinje cell loss and microglial activation in the cerebellar vermis that varied with injury severity. Together, these findings emphasize the vulnerability of the cerebellum to TBI. That a selective pattern of Purkinje cell loss occurs regardless of the type of injury suggests a generalized response that is a likely determinant of recovery and a target for therapeutic intervention.
临床证据表明，创伤性脑损伤（TBI）后小脑会受到损伤，实验研究也证实了这些观察结果。我们之前已经表明，在流体冲击性脑损伤后，小脑存在易损性，表现为浦肯野细胞丢失和小胶质细胞激活。在本研究中，我们在已被其他人证明对损伤严重程度敏感的生理和解剖学参数背景下，研究了分级控制性皮质撞击（CCI）损伤对小脑的影响。成年雄性大鼠接受轻度、中度或重度CCI损伤，并在7天后实施安乐死。我们首先在损伤后即刻使用包括呼吸暂停和血压在内的生理标准来验证初始损伤的严重程度。损伤严重程度增加与呼吸暂停发生率增加和死亡率升高相关。重度损伤还会导致短暂性高血压，随后是低血压，而较低级别的损伤则会导致即刻且持续的低血压。接下来，我们评估了分级损伤后皮质下神经元丢失的模式。同侧皮质、海马CA2/CA3和丘脑后外侧存在明显的神经元丢失，其与损伤严重程度相关，并与小胶质细胞激活平行。同样，小脑蚓部的浦肯野细胞丢失和小胶质细胞激活模式也因损伤严重程度而异。这些发现共同强调了小脑对TBI的易损性。无论损伤类型如何，都出现了选择性的浦肯野细胞丢失模式，这表明存在一种普遍的反应，这可能是恢复的决定因素和治疗干预的靶点。
