title: 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 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.
authors.affiliation: Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 49/Room 2A10, 49 Convent Drive, MSC 4476, Bethesda, MD 20892-4476, USA.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakayama
authors.forename: Kachikwu
authors.initials: K
authors.lastname: Illoh
authors.forename: Christl
authors.initials: C
authors.lastname: Ruetzler
authors.forename: Sungyoung
authors.initials: S
authors.lastname: Auh
authors.forename: Louis
authors.initials: L
authors.lastname: Sokoloff
authors.forename: John
authors.initials: J
authors.lastname: Hallenbeck
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D019040:E-Selectin / Q000276:immunology / Q000494:pharmacology*; D004660:Encephalitis / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000503:physiopathology; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology
chemical_list: D019040:E-Selectin