Monoclonal antibodies against ICAM-1 and CD18 attenuate cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits.
OBJECTIVE
Inflammatory responses have been implicated in the elaboration of several forms of central nervous system injury, including cerebral vasospasm after subarachnoid hemorrhage (SAH). A critical event participating in such responses is the recruitment of circulating leukocytes into the inflammatory site. Two of the key adhesion molecules responsible for the attachment of leukocytes to endothelial cells are intercellular adhesion molecule-1 (ICAM-1) and the common beta chain of the integrin superfamily (CD18). This study examined the effects of monoclonal antibodies on ICAM-1 and the effects of CD18 on cerebral vasospasm after SAH.


METHODS
A rabbit model of SAH was utilized to test the influence of intracisternally administered antibodies to ICAM-1 and CD18 on cerebral vasospasm. Antibodies were administered alone or in combination, and the cross-sectional area of basilar arteries was assessed histologically on day 2 post-SAH.


RESULTS
Treatment with antibodies to ICAM-1 or CD18 inhibited vasospasm by 22% and 27%, respectively. When administered together, the attenuation of vasospasm increased to 56%. All of these effects achieved statistical significance.


CONCLUSIONS
These findings provide the first evidence that the severity of cerebral vasospasm can be attenuated using monoclonal antibodies against ICAM-1 and CD18. The results reinforce the concept that cell-mediated inflammation plays an important role in cerebral vasospasm after SAH and suggest that therapeutic targeting of cellular adhesion molecules can be of benefit in treating cerebral vasospasm.
Bavbek
M
M
Department of Neurological Surgery and Virginia Neurological Institute, University of Virginia, Charlottesville 22908, USA.
Polin
R
R
Kwan
A L
AL
Arthur
A S
AS
Kassell
N F
NF
Lee
K S
KS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001488:Basilar Artery / Q000737:chemistry / Q000502:physiology; D001784:Blood Gas Analysis; D018821:CD18 Antigens / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000628:therapy; D008297:Male; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000628:therapy*; D014661:Vasoconstriction / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016207:Cytokines; D018799:Intercellular Adhesion Molecule-1