Neutrophils do not mediate blood-brain barrier permeability early after controlled cortical impact in rats.
Controlled cortical impact (CCI) produces blood-brain barrier (BBB) permeability and an acute inflammatory response in injured brain, associated with upregulation of cell adhesion molecules and accumulation of neutrophils. Nevertheless, the role of acute inflammation in the pathogenesis of BBB permeability after traumatic brain injury (TBI) is undefined. The purpose of this study was to examine the time course of acute inflammation and BBB permeability after CCI in rats and to determine the effect of neutrophil depletion on BBB permeability early after CCI. In the first protocol, four groups of rats (n = 4-7/group) were subjected to CCI. Expression of endothelial (E)-selectin on cerebrovascular endothelium, accumulation of neutrophils, and BBB permeability were measured in brain at 1, 4, 8, and 24 hours after injury by immunohistochemistry or spectrophotometric quantification of Evans blue. E-selectin upregulation and neutrophil accumulation in injured brain occurred at later times than maximal BBB permeability. In a second protocol, rats made neutropenic with a murine monoclonal IgM antibody (RP-3) specific for rat neutrophils were subjected to CCI, given Evans blue at 3.5 hours, and sacrificed at 4 hours after injury. Neutrophil depletion did not affect BBB permeability at 4 hours after CCI. We conclude that events other than those mediated by neutrophils initiate BBB permeability early after CCI.
Whalen
M J
MJ
Department of Anesthesiology, University of Pittsburgh, Pennsylvania, USA.
Carlos
T M
TM
Kochanek
P M
PM
Clark
R S
RS
Heineman
S
S
Schiding
J K
JK
Franicola
D
D
Memarzadeh
F
F
Lo
W
W
Marion
D W
DW
Dekosky
S T
ST
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000293:injuries*; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism; D007075:Immunoglobulin M / Q000633:toxicity; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009503:Neutropenia / Q000473:pathology / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors; D015854:Up-Regulation
D019040:E-Selectin; D007075:Immunoglobulin M