Blood-brain barrier permeability, neutrophil accumulation and vascular adhesion molecule expression after controlled cortical impact in rats: a preliminary study.
Previous studies in our laboratory have shown that controlled cortical impact (CCI) produces an acute inflammatory response in rat brain, including neutrophil accumulation and upregulation of cell adhesion molecules. The purpose of this study was to compare the time course of acute inflammation to blood-brain barrier (BBB) breakdown after (CCI) in rats.


METHODS
Male Wistar rats (n = 4-7/group) were subjected to CCI (2.5 mm depth, 4 m/s) and injected with Evans-blue dye (2%, 5 ml/kg) at 30 min, 3.5 h, 7.5 h, or 23.5 h after trauma. 30 min after dye injection rats were saline-perfused. BBB permeability was measured by spectrophotometric quantitation of Evans-blue in injured brain. Alternate cryostat sections from the anterior segment of the injured hemisphere were analyzed immunohistochemically for neutrophils (MoAb RP-3 vs rat neutrophils) or E-selectin (MoAb vs E-selectin). Neutrophils and E-selectin-positive blood vessels were quantitated by light microscopy in 100x cortical and hippocampal fields.


CONCLUSIONS
BBB breakdown was maximal early after CCI, whereas maximum E-selectin upregulation (8 h) and neutrophil accumulation (24 h) occurred later. Events other than acute inflammation initiate BBB permeability after CCI. Acute inflammation may contribute to BBB permeability at 4 h to 24 h after CCI.
Whalen
M J
MJ
Safar Center for Resuscitation Research, Brain Trauma Research Center, Pittsburgh, PA, USA.
Carlos
T M
TM
Kochanek
P M
PM
Heineman
S
S
D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology*; D002463:Cell Membrane Permeability / Q000276:immunology; D002540:Cerebral Cortex / Q000276:immunology / Q000293:injuries*; D019040:E-Selectin / Q000378:metabolism*; D016489:Head Injuries, Closed / Q000276:immunology*; D008297:Male; D020078:Neurogenic Inflammation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar
D019040:E-Selectin