Intranasal administration of E-selectin to induce immunological tolerization can suppress subarachnoid hemorrhage-induced vasospasm implicating immune and inflammatory mechanisms in its genesis

Abstract Evidence that inflammatory and immune mechanisms may have a critical role in the development of vasospasm after subarachnoid hemorrhage is accumulating. We examined, therefore, whether induction of immunological tolerance to the adhesion molecule that is uniquely expressed on activated endo...

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Bibliographic Details
Published in:Brain research 2007-02, Vol.1132 (1), p.177-184
Main Authors: Nakayama, Toshiyuki, Illoh, Kachikwu, Ruetzler, Christl, Auh, Sungyoung, Sokoloff, Louis, Hallenbeck, John
Format: Article
Language:English
Subjects:
Administration, Intranasal
Animals
Basilar artery
Basilar Artery - drug effects
Basilar Artery - immunology
Basilar Artery - physiopathology
Biological and medical sciences
Cell Adhesion - drug effects
Cell Adhesion - immunology
E-selectin
E-Selectin - immunology
E-Selectin - pharmacology
Encephalitis - complications
Encephalitis - immunology
Encephalitis - physiopathology
Endothelial Cells - drug effects
Endothelial Cells - immunology
Hypersensitivity, Delayed - immunology
Hypersensitivity, Delayed - physiopathology
Immune Tolerance - drug effects
Immune Tolerance - immunology
Immunomodulation
Immunosuppression - methods
Male
Medical sciences
Mucosal tolerance
Neurology
Rats
Rats, Inbred SHR
Subarachnoid hemorrhage
Subarachnoid Hemorrhage - complications
Subarachnoid Hemorrhage - immunology
Subarachnoid Hemorrhage - physiopathology
Treatment Outcome
Vascular diseases and vascular malformations of the nervous system
Vasospasm
Vasospasm, Intracranial - drug therapy
Vasospasm, Intracranial - immunology
Vasospasm, Intracranial - physiopathology
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Summary:Abstract Evidence that inflammatory and immune mechanisms may have a critical role in the development of vasospasm after subarachnoid hemorrhage is accumulating. We examined, therefore, whether induction of immunological tolerance to the adhesion molecule that is uniquely expressed on activated endothelium, E-selectin, could inhibit the vasospasm provoked by subarachnoid blood in a rat subarachnoid hemorrhage model. We found that intranasal instillation of E-selectin every other day for 10 days on a mucosal tolerization schedule suppressed delayed type hypersensitivity to E-selectin confirming tolerance to that molecule and markedly suppressed basilar artery spasm after subarachnoid hemorrhage. The results of this proof-of-concept study suggest that agents that can mimic the local effects of the mediators of mucosal tolerance could have therapeutic potential for the management of post-subarachnoid hemorrhage vasospasm.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2006.09.116