Fukuda K, Aihara N, Sagar S M, Sharp F R, Pitts L H, Honkaniemi J, Noble L J
Department of Neurosurgery, University of California, San Fracisco General Hospital, USA.
J Neurotrauma. 1996 May;13(5):255-66. doi: 10.1089/neu.1996.13.255.
In this study we examined the cerebellar response to mild traumatic brain injury by assessing microglial activation and Purkinje cell loss. Activated microglia were identified using the antibodies OX-42 and ED-1 as well as isolectin B4. The anti-Purkinje cell antibody PEP-19 was used to evaluate Purkinje cell loss after injury. The mechanism of cell injury was examined using a monoclonal antibody to the inducible 72-kDa heat shock protein. A monoclonal antibody to the N-terminal sequence of Fos was used as a marker for neuronal activation. There was progressive activation of microglia in the cerebellar vermis within a few days after forebrain injury. In coronal sections the processes of activated microglia were oriented in "stripes" perpendicular to the cortical surface. In sagittal sections the activated microglia were in irregularly shaped clusters or in a fan-like distribution that radiated from the Purkinje cell layer toward the cortical surface. There was a significant loss of Purkinje cells 7 days postinjury as compared to the control group. There was no evidence of induction of heat shock protein in the cerebellum. In addition, there was no evidence of induction of c-Fos protein in either the cerebellar cortex or inferior olivary nuclei within the first 3 h after injury. These studies demonstrate that a fluid percussive impact to the forebrain results in cerebellar damage. The close anatomical association between activated microglia and Purkinje cells suggests that Purkinje cell injury is the cause of the microglial activation. The mechanism of Purkinje cell death, however, remains unclear.
在本研究中，我们通过评估小胶质细胞激活和浦肯野细胞丢失来检测小脑对轻度创伤性脑损伤的反应。使用抗体OX - 42、ED - 1以及异凝集素B4来识别激活的小胶质细胞。抗浦肯野细胞抗体PEP - 19用于评估损伤后浦肯野细胞的丢失。使用针对诱导型72 kDa热休克蛋白的单克隆抗体来检测细胞损伤机制。针对Fos N端序列的单克隆抗体用作神经元激活的标志物。在前脑损伤后的几天内，小脑蚓部的小胶质细胞逐渐被激活。在冠状切片中，激活的小胶质细胞的突起呈垂直于皮质表面的“条纹”状排列。在矢状切片中，激活的小胶质细胞呈不规则形状的簇状或呈从浦肯野细胞层向皮质表面辐射的扇形分布。与对照组相比，损伤后7天浦肯野细胞有显著丢失。在小脑中没有热休克蛋白诱导的证据。此外，在损伤后的前3小时内，在小脑皮质或下橄榄核中均没有c - Fos蛋白诱导的证据。这些研究表明，前脑的流体冲击会导致小脑损伤。激活的小胶质细胞与浦肯野细胞之间紧密的解剖学关联表明，浦肯野细胞损伤是小胶质细胞激活的原因。然而，浦肯野细胞死亡的机制仍不清楚。
