Effect of traumatic brain injury in mice deficient in intercellular adhesion molecule-1: Assessment of histopathologic and functional outcome

Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule of the i mmunoglobulin family expressed on endothelial cells that is upregulated in brain as part of the acute inflammatory response to traumatic brain injury (TBI). ICAM-1 mediates neurologic injury in experimental meningitis and str oke; however, its role in the pathogenesis of TBI is unknown. We hypothesiz ed that mutant mice deficient in ICAM-1 (-/-) would have decreased neutroph il accumulation, diminished histologic injury, and improved functional neur ologic outcome versus ICAM-1 +/+ wild type control mice after TBI. Anesthet ized ICAM-1 -/- mice and wild-type controls were subjected to controlled co rtical impact (CCI, 6 m/sec, 1.2 mm depth). Neutrophils in brain parenchyma and ICAM-1 on vascular endothelium were assessed by immunohistochemistry i n cryostat brain sections from the center of the contusion 24 h after TBI ( n = 4/group). Separate groups of wild-type and ICAM-1-deficient mice (n = 9 -10/group) underwent motor (wire grip test, days 1-5) and cognitive (Morris water maze [MWM], days 14-20) testing. Lesion volume was determined by ima ge analysis 21 days following TBI. Robust expression of ICAM-1 was readily detected in choroid plexus and cerebral endothelium at 24 h in ICAM-1 +/+ m ice but not in ICAM-1 -/- mice, No differences between groups were observed in brain neutrophil accumulation (9.4 +/- 2.2 versus 11.1 +/- 3.0 per x 10 0 field, -/- versus +/+), wire grip score, MWM latency, or lesion volume (7 .24 +/- 0.63 versus 7.21 +/- 0.45 mm(3), -/- versus +/+). These studies fai l to support a role for ICAM-1 in the pathogenesis of TBI.