P-selectin blockade following fluid-percussion injury: behavioral and immunochemical sequelae.
Traumatic brain injury (TBI) can cause polymorphonuclear leukocyte (PMN) migration into brain parenchyma, mediating various cytodestructive mechanisms. We examined the effect of blocking leukocyte/endothelial cell adhesion molecules (CAMs) on the anatomic and behavioral sequelae in lateral fluid-percussion injury in rats. Monoclonal antibodies (MAb) directed against a functional (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 underwent myeloperoxidase (MPO) assay in the brain parenchyma and a third set was used to examine neutrophil migration using the MAb RP-3. Time in quadrant, but not escape latency or proximity improved with PB1.3 (p < 0.05). Similarly, PB1.3 reduced MPO levels after injury (p < 0.05), in the ipsilateral cortex. No significant difference occurred in neutrophil counts in cortex, corpus callosum, hippocampus, and thalamus between injured only rats and injured rats treated with PB1.3. Quantitative analysis of cholinergic cells in the medial septum showed a protective effect by PB1.3. Densitometry readings of GFAP and OX-42 immunolabeling revealed no discernible differences between the treated and untreated injured rats. Qualitatively, there was no difference in microglia or astrocyte response to treatment. Treatment with P-selectin blockade in brain-injured rats may reduce PMN migration into brain, help preserve cholinergic immunolabeling of medial septal nucleus neurons, and may alleviate mnemonic deficits.
Grady
M S
MS
Department of Neurological Surgery, University of Washington School of Medicine, Seattle 98104, USA.
Cody
R F
RF
Maris
D O
DO
McCall
T D
TD
Seckin
H
H
Sharar
S R
SR
Winn
H R
HR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001522:Behavior, Animal / Q000502:physiology*; D001798:Blood Proteins; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000276:immunology* / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D019007:P-Selectin / Q000276:immunology / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley