Rancan M, Otto V I, Hans V H, Gerlach I, Jork R, Trentz O, Kossmann T, Morganti-Kossmann M C
Division of Research, Department of Surgery, University Hospital, Zurich, Switzerland.
J Neurosci Res. 2001 Mar 1;63(5):438-46. doi: 10.1002/1097-4547(20010301)63:5<438::AID-JNR1039>3.0.CO;2-P.
The pathophysiology of traumatic axonal injury (TAI) is only partially understood. In this study, we investigated the inflammatory response as well as the extent of neurological deficit in a rat model of traumatic brain injury (TBI). Forty-two adult rats were subjected to moderate impact-acceleration brain injury and their brains were analyzed immunohistochemically for ICAM-1 expression and neutrophil infiltration from 1 hr up to 14 days after trauma. In addition, the chemotactic factors MIP-2 and MCP-1 were measured in brain homogenates by ELISA. For evaluating the neurological deficit, three sensorimotor tests were applied for the first time in this model. In the first 24 hr after trauma, the number of ICAM-1 positive vessels increased up to 4-fold in cortical and subcortical regions compared with sham operated controls (P < 0.05). Maximal ICAM-1 expression (up to 8-fold increase) was detected after 4 days (P < 0.001 vs. 24 hr), returning to control levels in all brain regions by 7 days after trauma. MCP-1 was elevated between 4 hr and 16 hr post-injury as compared with controls. In contrast, neither neutrophil infiltration nor elevation of MIP-2, both events relevant in focal brain injury, could be detected. In all neurological tests, a significant deficit was observed in traumatized rats as compared with sham operated animals from Day 1 post-injury (grasping reflex of the hindpaws: P < 0.001, vibrissae-evoked forelimb placing: P = 0.002, lateral stepping: P = 0.037). In conclusion, after moderate impact acceleration brain injury ICAM-1 upregulation has been demonstrated in the absence of neutrophil infiltration and is paralleled by a selective induction of chemokines, pointing out that individual and distinct inflammatory events occur after diffuse vs. focal TBI.
创伤性轴索损伤（TAI）的病理生理学仅得到部分理解。在本研究中，我们在创伤性脑损伤（TBI）大鼠模型中研究了炎症反应以及神经功能缺损的程度。42只成年大鼠接受中度撞击-加速性脑损伤，并在创伤后1小时至14天对其大脑进行免疫组织化学分析，以检测ICAM-1表达和中性粒细胞浸润情况。此外，通过酶联免疫吸附测定法（ELISA）测量脑匀浆中的趋化因子MIP-2和MCP-1。为评估神经功能缺损，首次在该模型中应用了三项感觉运动测试。创伤后的头24小时内，与假手术对照组相比，皮质和皮质下区域ICAM-1阳性血管数量增加了4倍（P < 0.05）。4天后检测到ICAM-1表达达到最大值（增加了8倍）（与24小时相比，P < 0.001），创伤后7天所有脑区的ICAM-1表达恢复到对照水平。与对照组相比，损伤后4小时至16小时MCP-1升高。相反，未检测到与局灶性脑损伤相关的中性粒细胞浸润和MIP-2升高。在所有神经学测试中，与假手术动物相比，创伤大鼠自损伤后第1天起出现明显的功能缺损（后爪抓握反射：P < 0.001，触须诱发的前肢放置：P = 0.002，侧步：P = 0.037）。总之，中度撞击加速性脑损伤后，在无中性粒细胞浸润的情况下已证实ICAM-1上调，并且与趋化因子的选择性诱导同时发生，这表明弥漫性与局灶性TBI后发生了个体和独特的炎症事件。
