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The Role of Nitric Oxide in Homocysteine Thiolactone-Induced Seizures in Adult Rats

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Abstract

The role of NO in epileptogenesis has been studied in different experimental models, and the reported results have been highly contradictory. The current study aimed to determine the role of NO in mechanisms of d,l-homocysteine-thiolactone (H) induced seizures by testing the action of l-arginine (NO precursor) and l-NAME (NOS inhibitor) on behavioral and electroencephalographic (EEG) manifestations of H-induced seizures. The same holds true with the brain Na+/K+- and Mg2+-ATPase activity in adult male Wistar rats. We showed that the pretreatment with l-arginine (300, 600 and 800 mg/kg, i.p.) in a dose-dependent manner significantly decreased lethality, seizure incidence and a number of seizure episodes and prolonged latency time to the first seizure elicited by a convulsive dose of H (8 mmol/kg, i.p.). l-Arginine (800 mg/kg) completely reversed the inhibitory effect of H on the Na+/K+-ATPase activity in the hippocampus, the cortex and the brain stem and decreased the H-induced spike-and- wave discharges (SWD) formation in EEG. On the other hand, pretreatment with l-NAME (200, 500 and 700 mg/kg, i.p.) potentiated a subconvulsive dose of H (5.5 mmol/kg, i.p) by increasing incidence and severity determined by a descriptive-rating scale (0–4) and shortening the latency time to the first seizure. The l-NAME reversed H-induced alterations in the Na+/K+-ATPase activity in the cortex and the brain stem but not in the hippocampus. At last, the potentiated SWD appearance in EEG and an increased number of lethal outcomes occurred. In the present work, the modulation of NO levels, with the NO precursor and NOS inhibitor, was shed more light on its mechanism of action and answered the question whether NO could be included in the list of anticonvulsant agents in the d,l-homocysteine thiolactone experimental model of seizures in adult rats.

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Acknowledgments

This work was supported by the Ministry of Science and Technological Development of Serbia, Grant No. 145029B.

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  1. Laboratory of Neurophysiology, Institute of Medical Physiology “Richard Burian”, School of Medicine, University of Belgrade, Višegradska 26/II, 11000, Belgrade, Serbia

    Dragan Hrnčić, Aleksandra Rašić-Marković, Djuro Macut, Dragan Djuric & Olivera Stanojlović

  2. Department of Medical Chemistry, School of Medicine, University of Belgrade, 11000, Belgrade, Serbia

    Danijela Krstić

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  1. Dragan Hrnčić
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  2. Aleksandra Rašić-Marković
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  3. Danijela Krstić
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  6. Olivera Stanojlović
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Correspondence to Olivera Stanojlović.

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Hrnčić, D., Rašić-Marković, A., Krstić, D. et al. The Role of Nitric Oxide in Homocysteine Thiolactone-Induced Seizures in Adult Rats. Cell Mol Neurobiol 30, 219–231 (2010). https://doi.org/10.1007/s10571-009-9444-9

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