title: Effect of traumatic brain injury in mice deficient in intercellular adhesion molecule-1: assessment of histopathologic and functional outcome.
abstract: Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule of the immunoglobulin 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 stroke; however, its role in the pathogenesis of TBI is unknown. We hypothesized that mutant mice deficient in ICAM-1 (-/-) would have decreased neutrophil accumulation, diminished histologic injury, and improved functional neurologic outcome versus ICAM-1 +/+ wild type control mice after TBI. Anesthetized ICAM-1 -/- mice and wild-type controls were subjected to controlled cortical impact (CCI, 6 m/sec, 1.2 mm depth). Neutrophils in brain parenchyma and ICAM-1 on vascular endothelium were assessed by immunohistochemistry in 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 image 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 +/+ mice 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 x100 field, -/- versus +/+), wire grip score, MWM latency, or lesion volume (7.24 +/- 0.63 versus 7.21 +/- 0.45 mm3, -/- versus +/+). These studies fail to support a role for ICAM-1 in the pathogenesis of TBI.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh, Pennsylvania, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Whalen
authors.forename: T M
authors.initials: TM
authors.lastname: Carlos
authors.forename: C E
authors.initials: CE
authors.lastname: Dixon
authors.forename: J K
authors.initials: JK
authors.lastname: Schiding
authors.forename: R S
authors.initials: RS
authors.lastname: Clark
authors.forename: E
authors.initials: E
authors.lastname: Baum
authors.forename: H Q
authors.initials: HQ
authors.lastname: Yan
authors.forename: D W
authors.initials: DW
authors.lastname: Marion
authors.forename: P M
authors.initials: PM
authors.lastname: Kochanek
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D003072:Cognition Disorders / Q000503:physiopathology; D018450:Disease Progression; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009069:Movement Disorders / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology; D013997:Time Factors
chemical_list: D018799:Intercellular Adhesion Molecule-1