title: Neuronal RAGE expression modulates severity of injury following transient focal cerebral ischemia.
abstract: Inflammation has a significant role in the neurological injury that follows stroke. The receptor for advanced-glycation end products (RAGE) is a multiligand member of the immunoglobulin superfamily that has been implicated in multiple neuronal and inflammatory stress processes. To directly test the role of neuronal RAGE in stroke, we employed two cohorts of transgenic mice, one over-expressing full-length functional human RAGE in neurons, and the other a human RAGE transgene in which deletion of the cytoplasmic domain of the receptor in neurons suppresses signal transduction stimulated by ligands (referred to as dominant negative or DN-RAGE). We found a statistically significant increase in stroke volume in the RAGE over-expressing cohort compared to normal controls, and a trend towards decreased stroke volume in the DN RAGE cohort. These results indicate that RAGE signaling directly contributes to pathology in cerebral ischemia.
authors.affiliation: Department of Neurological Surgery, 710 West 168th Street, Room 431, Columbia University, New York, New York 10032, USA.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Hassid
authors.forename: M Nathan
authors.initials: MN
authors.lastname: Nair
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Ducruet
authors.forename: Marc L
authors.initials: ML
authors.lastname: Otten
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Komotar
authors.forename: David J
authors.initials: DJ
authors.lastname: Pinsky
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
authors.forename: Shi Fang
authors.initials: SF
authors.lastname: Yan
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic