Monoclonal antibodies against ICAM-1 and CD18 attenuate cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits

Murad Bavbek, Richard Polin, Aij Lie Kwan, Adam Arthur, Neal F. Kassell, Kevin S. Lee

Research output: Contribution to journalArticle

101 Citations (Scopus)

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 β 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.

Original languageEnglish (US)
Pages (from-to)1930-1935
Number of pages6
JournalStroke
Volume29
Issue number9
StatePublished - Sep 1 1998

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Intracranial Vasospasm
Subarachnoid Hemorrhage
Intercellular Adhesion Molecule-1
Monoclonal Antibodies
Rabbits
Antibodies
Leukocytes
Nervous System Trauma
Basilar Artery
Cell Adhesion Molecules
Integrins
Central Nervous System
Endothelial Cells
Inflammation

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Monoclonal antibodies against ICAM-1 and CD18 attenuate cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. / Bavbek, Murad; Polin, Richard; Kwan, Aij Lie; Arthur, Adam; Kassell, Neal F.; Lee, Kevin S.

In: Stroke, Vol. 29, No. 9, 01.09.1998, p. 1930-1935.

Research output: Contribution to journalArticle

Bavbek, Murad ; Polin, Richard ; Kwan, Aij Lie ; Arthur, Adam ; Kassell, Neal F. ; Lee, Kevin S. / Monoclonal antibodies against ICAM-1 and CD18 attenuate cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. In: Stroke. 1998 ; Vol. 29, No. 9. pp. 1930-1935.
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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 β 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.",
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