title: S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke.
abstract: Preservation of endothelial functions with low-dose nitric oxide (NO) and inhibition of excessive production of NO from inducible NO synthase (iNOS) is a potential therapeutic approach for acute stroke. Based on this hypothesis, an NO modulator, S-nitrosoglutathione (GSNO) was used, which provided neuroprotection in a rat model of focal cerebral ischemia. Administration of GSNO after the onset of ischemia reduced infarction and improved cerebral blood flow. To understand the mechanism of protection, the involvement of inflammation in ischemic brain injury was examined. Treatment with GSNO reduced the expression of tumor necrosis factor-alpha, interleukin-1beta, and iNOS; inhibited the activation of microglia/macrophage (ED1, CD11-b); and downregulated the expression of leukocyte function-associated antigen-1 and intercellular adhesion molecule-1 in the ischemic brain. The number of apoptotic cells (including neurons) and the activity of caspase-3 were also decreased after GSNO treatment. Further, the antiinflammatory effect of GSNO on expression of iNOS and activation of NF-kappaB machinery in rat primary astrocytes and in the murine microglial cell line BV2 was tested. Cytokine-mediated expression of iNOS and activation of NF-kappaB were inhibited by GSNO treatment. That GSNO protects the brain against ischemia/reperfusion injury by modulating NO systems, resulting in a reduction in inflammation and neuronal cell death was documented by the results.
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425, USA. khanm@musc.edu
authors.forename: Mushfiquddin
authors.initials: M
authors.lastname: Khan
authors.forename: Bipanjeet
authors.initials: B
authors.lastname: Sekhon
authors.forename: Shailendra
authors.initials: S
authors.lastname: Giri
authors.forename: Manu
authors.initials: M
authors.lastname: Jatana
authors.forename: Anne G
authors.initials: AG
authors.lastname: Gilg
authors.forename: Kamesh
authors.initials: K
authors.lastname: Ayasolla
authors.forename: Chinnasamy
authors.initials: C
authors.lastname: Elango
authors.forename: Avtar K
authors.initials: AK
authors.lastname: Singh
authors.forename: Inderjit
authors.initials: I
authors.lastname: Singh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control; D026422:S-Nitrosoglutathione / Q000494:pharmacology*; D020521:Stroke / Q000150:complications* / Q000473:pathology
chemical_list: D016207:Cytokines; D018696:Neuroprotective Agents; D026422:S-Nitrosoglutathione