title: NOx and ADMA changes with focal ischemia, amelioration with the chaperonin GroEL.
abstract: Both nitric oxide and asymmetric dimethylarginine (ADMA) play a critical role in the regulation of cerebral blood flow, though their neuroprotective and cytotoxic effects are still under investigation. In this study, we found that nitrate/nitrite (NOx) levels in plasma, ischemic brain tissue, and cerebrospinal fluid (CSF) increased significantly 24h after 2h transient middle cerebral artery occlusion (MCAO) in rats. ADMA levels were unchanged in plasma, but decreased significantly in CSF 24h following MCAO. The CSF ADMA/NOx ratio decreased markedly following ischemia. Rats protected by expression of the chaperonin GroEL or its folding deficient mutant D87K had lower plasma NOx levels at 24h reperfusion. ADMA, NO, and their ratio in CSF merit further study as biomarkers for ischemic brain injury.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
authors.forename: Bingyin
authors.initials: B
authors.lastname: Wang
authors.forename: Kirandeep
authors.initials: K
authors.lastname: Kaur
authors.forename: Melanie F
authors.initials: MF
authors.lastname: Kho
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.forename: Rona G
authors.initials: RG
authors.lastname: Giffard
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D019610:Cytoprotection / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000097:blood* / Q000134:cerebrospinal fluid; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015415:Biomarkers; D018834:Chaperonin 60; C487735:dimethylarginine; D009569:Nitric Oxide; D001120:Arginine