Mercaptoethylguanidine inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expressions induced in rats after fluid-percussion brain injury.
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.
Moochhala
Shabbir M
SM
Defence Medical and Environmental Research Institute@DSO, Singapore. nmiv19@nus.edu.sg
Lu
Jia
J
Xing
Michelle Chang Ker
MC
Anuar
Farhana
F
Ng
Kian Chye
KC
Yang
Kerwin Low Siew
KL
Whiteman
Matthew
M
Atan
Shirhan
S
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D011312:Pressure; D051381:Rats; D012965:Sodium Chloride / Q000008:administration & dosage
D004791:Enzyme Inhibitors; D006146:Guanidines; D018696:Neuroprotective Agents; D012965:Sodium Chloride; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C100078:2-mercaptoethylguanidine