Upregulation of ICAM-1 and MCP-1 but not of MIP-2 and sensorimotor deficitin response to traumatic axonal injury in rats

The pathophysiology of traumatic axonal injury (TAI) is only partially unde rstood. In this study, we investigated the inflammatory response as well as the extent of neurological deficit in a rat model of traumatic brain injur y (TBI). Forty-two adult rats were subjected to moderate impact-acceleratio n brain injury and their brains were analyzed immunohistochemically for ICA M-1 expression and neutrophil infiltration from 1 hr up to 14 days after tr auma. 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 f irst 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 neutr ophil infiltration nor elevation of MIP-2, both events relevant in focal br ain injury, could be detected. In all neurological tests, a significant def icit was observed in traumatized rats as compared with sham operated animal s from Day 1 post-injury (grasping reflex of the hindpaws: P < 0.001, vibri ssae-evoked forelimb placing: P = 0.002, lateral stepping: P = 0.037). In c onclusion, after moderate impact acceleration brain injury ICAM-1 upregulat ion has been demonstrated in the absence of neutrophil infiltration and is paralleled by a selective induction of chemokines, pointing out that indivi dual and distinct inflammatory events occur after diffuse vs, focal TBI. (C ) 2001 Wiley-Liss, Inc.