Monoclonal Antibodies Against ICAM-1 and CD18 Attenuate Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage in Rabbits

Abstract

Background and Purpose-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 ␤ 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.

Cerebrovascular Inflammation Following Subarachnoid Hemorrhage

“…Intracisternal injection of antibodies to ICAM-1 and CD18 in rabbits after SAH inhibited VS by 22% and 27%, respectively, increased to 56% by combined injection (216). This observation suggests that the recruitment of inflammatory cells into the subarachnoid environment may play an important role.…”

“…Intraperitoneal administration of anti-ICAM-1 monoclonal antibody decreases the ICAM-1-mediated interaction between endothelial cells and macrophages and granulocytes after a perivascular hemorrhage in a rat model of arterial VS (215). Intracisternal injection of antibodies to ICAM-1 or CD18, which are two of the key adhesion molecules responsible for the attachment of leukocytes to endothelial cells, inhibit VS in a rabbit model of SAH (216). In addition, T-lymphocytes and macrophages were observed in the subarachnoid space with a peak appearance in brain tissue at 2 days post-SAH (217).…”

Inhibitory Effect With Antisense Mitogen-Activated Protein Kinase Oligodeoxynucleotide Against Cerebral Vasospasm in Rats

“…15,16 The basilar arteries were transected at the same point: two thirds of the distance from the proximal side to avoid the arterial branches. These sections were prepared over 200 m. Three cross-sections of each vessel were selected randomly for measurement.…”

Serum and cerebrospinal fluid concentrations of E-selectin in patients with aneurysmal subarachnoid hemorrhage

“…pearance or up-regulation of CAMs has been observed in a variety of central nervous system (CNS) diseases (5)(6)(7)(8) and the therapeutic approaches blocking leukocyte-endothelium interactions have provided encouraging results, suggesting that these molecules have a pivotal role (9)(10)(11)(12)(13).…”