L-selectin inhibition does not reduce injury in a rabbit model of transient focal cerebral ischemia.
Neutrophils are known to mediate injury in acute ischemic stroke especially during reperfusion. Migration of neutrophils into regions of ischemic injury involves binding to the endothelial cells via interactions with various adhesion molecules. One adhesion molecule, L-selectin, is found on the surface of leukocytes, and is shed prior to leukocyte infiltration. We studied whether a humanized antibody to L-selectin (HuDREG200) might limit ischemic injury in an experimental stroke model. New Zealand White rabbits underwent transorbital occlusion of the left middle cerebral, anterior cerebral and internal carotid arteries using aneurysm clips for 2 h followed by 6 h of reperfusion. Treatment with a saturating dose (4 mg kg-1) of HuDREG200 (n = 8) or vehicle (n = 8) was administered 20 min after occlusion and given as a single i.v. bolus. Hemispheric ischemic neuronal damage (IND) as seen on hematoxylin and eosin stained sections was no different between groups (HuDREG200, 23.3% +/- 6%; vehicle, 19.6% +/- 6%; mean +/- SEM, n.s., t-test). Immunohistochemical staining with neutrophil elastase confirmed the presence of neutrophils within regions of IND in control brains, but treatment did not alter their numbers within ischemic tissue. We conclude that antagonism of neutrophil adhesion at the level of L-selectin does not alter ischemic injury in experimental stroke.
Yenari
M A
MA
Department of Neurosurgery, Stanford University Medical Center, Palo Alto, CA, USA. yenari@stanford.edu
Sun
G H
GH
Kunis
D M
DM
Onley
D
D
Vexler
V
V
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D019041:L-Selectin / Q000276:immunology* / Q000378:metabolism*; D007958:Leukocyte Count; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D011817:Rabbits
D019041:L-Selectin