Nitric Oxide Synthase Expression After Traumatic Brain Injury And Neuroprotection With Aminoguanidine Treatments In Rats

Objective: We investigated the time course of nitric oxide synthase(NOS) enzymatic activity and linmunocytochemical localization of inducible nitric oxide(INOS) expression after traumatic brain injury(TBI), as well as the possible role of LNOS in the pathogenesis of TB! Materials and Methods: Male Sprague-Dawley rats were anesthetized and underwent moderate parasagittal weight-drop model brain injury, Rats were decapitated 5 minutes, 6 hours, l2hours, ldays, 2 days, 4 days, 7days, 1 Odayslater, and no enzymatic activities were measured(n=6?). To determine whether nitric oxide produced by iNOS contributed to the bistopathological consequences of TB!, inhibition of lNos activity using aminoguanidine (intraperiotoneal injections of 1 00mg/kg aminoguanidine [n=9] or vehicle [n=8j, twice each day)was conducted for three days. Results: Significantly elevated NOS activity was detected at 6 hours (35.01 ? 0.07U/mg) the most robust increase, and at 24 hours NOS activity turned back to normal, and at 7 days after TB! the NOS activity increased to (31.58 ?0.0%/mg) in the injured parietal cerebral cortex. Immunostaining for 1NOS at 6 hours, 12 hours, 1 days, 2 days, 4 days, 7 days after TB!, revealed the major sources of iNOS expression were astrocytes and neurons. Administration of aminoguanidine reduced the total necrotic neuron counts, and obviously improved the function of neuron. Conclusion: These data indicate the NOS is expressed after moderate parasagittal weight-drop brain injury, in a time-dependent manner, and that inhibition of iNOS synthesis improves histopathological outcomes. Thus, inhibition of iNOS activation may represent a potential therapeutic strategy for the treatment of TB!. 3...