P-selectin blockade following fluid-percussion injury: Behavioral and immunochemical sequelae

Traumatic brain injury (TBI) can cause polymorphonuclear leukocyte (PMN) mi gration into brain parenchyma, mediating various cytodestructive mechanisms . We examined the effect of blocking leukocyte/endothelial cell adhesion mo lecules (CAMs) on the anatomic and behavioral sequelae in lateral fluid-per cussion injury in rats. Monoclonal antibodies (MAb) directed against a func tional (PB1.3) or nonfunctional (PNB1.6) epitope on endothelial P-selectin were used as treatments. Subjects were tested in the Morris water maze (MWM ) at 7 and 14 days postinjury then immunohistochemistry was performed using antibodies that recognize ChAT, GFAP and OX-42. A second set of animals un derwent myeloperoxidase (MPO) assay in the brain parenchyma and a third set was used to examine neutrophil migration using the MAb RP-3. Time in quadr ant, but not escape latency or proximity improved with PB1.3 (p < 0.05). Si milarly, PB1.3 reduced MPO levels after injury (p < 0.05), in the ipsilater al cortex. No significant difference occurred in neutrophil counts in corte x, corpus callosum, hippocampus, and thalamus between injured only rats and injured rats treated with PB1.3. Quantitative analysis of cholinergic cell s in the medial septum showed a protective effect by PB1.3. Densitometry re adings of GFAP and OX-42 immunolabeling revealed no discernible differences between the treated and untreated injured rats. Qualitatively, there was n o difference in microglia or astrocyte response to treatment. Treatment wit h P-selectin blockade in brain-injured rats may reduce PMN migration into b rain, help preserve cholinergic immunolabeling of medial septal nucleus neu rons, and may alleviate mnemonic deficits.