Abstract

Background: Perinatal hypoxia is one of the most common causes of neonatal seizures. Nitric oxide (NO) has been involved in the pathophysiology of seizures. Furthermore, NO as well as nuclear factor-kB (NF-kB) have been implicated in the oxidative stress-induced neurodegeneration, associated with hypoxia and/or kainic acid (KA). Objective: The aim of the present study is to examine the role of 7-Nitroindazole (7NI) on hypoxic (H) and KA-induced seizures during early life. The expression of NF-kB has been also examined. Methods: Wistar rats (P10–11) were divided into 4 groups: A (H), B (H/KA), C (H/KA and 7NI) and D (control, vehicle). Hypoxia was induced by decreasing O2 concentration from 7% to 4% within 15 minutes. At P21–22, rats of groups B and C were administered with KA (10mg/kg i.p). Animals of group C were pre-treated with 7NI (50mg/kg i.p). Histological assessment was performed at P24 with hematoxylin-eosin staining and cell counts in the hippocampal area. NF-kB expression was examined by immunohistochemistry. Results: Histologic evaluation revealed significantly decreased cell loss in 7NI treated group, compared with group B (10.1%±3.5 and 25.1%±10.5 respectively p<0.05). In control group NF-kB immunostaining was slight and restricted to the cytoplasm. In H/KA group over-expression of NF-kB was clearly observed at 4 hr, following KA administration, reduced in 24 hrs and almost totally abolished in 48 hrs. NF-kB immunoreactivity was localized mainly in the cytoplasm of neuronal, glial and endothelial cells. Dense nuclear immunostaining of NF-kB was observed in damaged neurons and reactive astrocytes of hippocampal area. There was no obvious difference in NF-kB staining between H/KA group and animals pre-treated with 7NI Conclusion: According to our results administration of 7NI, a selective inhibitor of nNOS, clearly diminished seizures-induced damage in the hippocampus, which might indicate a possible role of NO in the pathophysiology of prolonged seizures during infancy. Additionally, alteration of NF-kB expression points to a potential implication of NF-kB in mechanisms of seizures that may be correlated with NO.

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