Mercaptoethylguanidine inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expressions induced in rats after fluid-percussion brain injury

• Published in: The journal of trauma Vol. 59; no. 2; p. 450
• Main Authors: Moochhala, Shabbir M, Lu, Jia, Xing, Michelle Chang Ker, Anuar, Farhana, Ng, Kian Chye, Yang, Kerwin Low Siew, Whiteman, Matthew, Atan, Shirhan
• Format: Journal Article
• Language: English
• Published: United States 01.08.2005
• Subjects: Animals; Brain Injuries - metabolism; Cerebral Cortex - metabolism; Cyclooxygenase 2 - metabolism; Enzyme Inhibitors - pharmacology; Guanidines - pharmacology; Immunohistochemistry; Male; Neuroprotective Agents - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase Type II - metabolism; Pressure; Rats; Sodium Chloride - administration & dosage
• ISSN: 0022-5282; 1529-8809
• DOI: 10.1097/01.ta.0000174858.79847.6d

The present study examined the temporal expression of nitric oxide synthase (iNOS) and cyclo-oxygenase (COX)-2 in rat brains after traumatic brain injury (TBI). We studied the effects of mercaptoethylguanidine (MEG), a dual inhibitor of the inducible iNOS and COX with scavenging effect on peroxynitrite, on physiologic variables, brain pathogenesis, and neurologic performance in rats after a lateral fluid percussive-induced TBI. Mean arterial blood pressure and percentage cerebral tissue perfusion in MEG-treated TBI rats showed significant improvement when compared with TBI rats. Immunohistochemical analysis showed a marked number of iNOS and COX-2 immunopositive cells in the cerebral cortex ipsilateral to the injury in TBI rats when compared with MEG-treated TBI rats. MEG also significantly decreased the number of hyperchromatic and shrunken cortical neurons when compared with TBI rats' brain nitrate/nitrite, and prostaglandin E2 levels were attenuated in MEG-treated TBI rats when compared with TBI rats. It is therefore suggested that treatment of MEG via inhibition of iNOS and COX-2 might contribute to improved physiologic variables, neuronal cell survival, and neurologic outcome after TBI.