Journal
NEUROBIOLOGY OF DISEASE
Volume 36, Issue 3, Pages 435-444Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2009.08.008
Keywords
Developing hippocampus; Oxidative stress; Hypoxia-induced seizures; Rodent model; NAP; Neuroprotection
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Funding
- Brazilian Agencies Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Fundacao de Amparo a Pesquisa do Rio Grande do Sul (FAPERGS)
- Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS)
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Neonatal seizures in which hypoxic-ischemic encephalopathy is the main triggering etiology have a challenging diagnosis and limited efficacy of treatment. NAP (NAPVSIPQ) has shown extensive neuroprotective and antioxidant capacity in vitro and in vivo. To evaluate its neuroprotective role in the context of seizures associated with perinatal hypoxia, we assessed the integrity of DNA and lipid membranes as well as the redox status in the hippocampus of 10-day-old rats exposed to hypoxia-induced seizures (HS) with and without NAP treatment. Rats were exposed to transient global hypoxia (12 min exposure to 5-7% 02 was able to induce electrographic seizures) or room air with subsequent intraperitoneal NAP (0.03, 0.3 or 3 mu g/g) or vehicle administration. Results showed elevated DNA damage immediately after the insult until 72 h post-HS, while oxidized bases were only detected 3, 6 and 24 h later. In addition, thiobarbituric acid reactive species peaked at 6 h in parallel with decreased levels of reduced glutathione between 3 and 72 h post-HS insult. Our findings expand on the knowledge about the time course of HS-induced oxidative damage and demonstrate for the first time that a single NAP injection dose-dependently prevents HS-induced oxidative damage to DNA and lipid membranes, in correlation with modulation of the glutathione system. Hence, NAP may represent a promising therapeutic strategy for avoiding HS-induced oxidative damage. (C) 2009 Elsevier Inc. All rights reserved.
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