title: Administration of S-methyl-L-thiocitrulline protects against brain injuries after intracerebral hemorrhage.
abstract: Although intracerebral hemorrhage (ICH) increases the level of glutamate in the perihematomal area and cerebral spinal fluid (CSF) in the ICH acute phase, it is unclear whether elevated glutamate activates neuronal nitric oxide synthase (nNOS) in the ICH brain and whether nNOS is an important target for ICH treatment. Here, we assessed the role of the nNOS inhibitor S-methyl-l-thiocitrulline (SMTC) in the activity of NADPH-d and ICH-induced brain injuries. An autologous blood intracerebral infusion model in male rats was used. All of the rats were sacrificed 24h after ICH. ICH increased NADPH-d activity in the striatum. Administering SMTC 3h after ICH decreased the activity of NADH-d (p<0.05 vs. the ICH group). The activation of gelatinolytic enzymes in the perihematomal region of the striatum was reduced by SMTC treatment (p<0.01, vs. the ICH group). The loss of laminin- and occludin-stained vessels was significant in perihematomal regions after 24h of ICH and was significantly attenuated by the administration of SMTC (p<0.01 for laminin, p<0.05 for occluding, compared with the ICH group). Neuronal death and neurological deficits after ICH were also decreased in SMTC treatment rats (p<0.01, vs. the ICH group). The results suggest that the administration of the nNOS inhibitor SMTC after ICH protects against ICH-induced brain injuries and improves neurological function.
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, OH 45267-0532, USA. Electronic address: lua@ucmail.uc.edu.
authors.forename: A
authors.initials: A
authors.lastname: Lu
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, OH 45267-0532, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Wagner
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, OH 45267-0532, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Broderick
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, OH 45267-0532, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Clark
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology; D002956:Citrulline / Q000031:analogs & derivatives* / Q000494:pharmacology; D003342:Corpus Striatum / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D011187:Posture / Q000502:physiology; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007797:Laminin; D018696:Neuroprotective Agents; D062793:Occludin; C568987:Ocln protein, rat; D002956:Citrulline; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase; D013890:Thiourea; C086717:S-methylthiocitrulline
keywords: S-methyl-l-thiocitrulline; brain injury; intracerebral hemorrhage; rats
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