the effect of rosmarinic acid on apoptosis and nnos immunoreactivity following intrahippocampal kainic acid injections in rats

Introduction: kainic acid (ka) is an ionotropic glutamate receptor agonist. ka can induce neuronal overactivity and excitotoxicity. rosmarinic acid (ra) is a natural polyphenolic compound with antioxidant, anti-apoptotic, anti-neurodegenerative, and anti-inflammatory properties. this study aimed to assess the effect of ra on apoptosis, nnos-positive neurons number, as well as mitogen-activated protein kinase (mapk) and cyclooxygenase-2 (cox- 2) immunoreactivity, following intrahippocampal kainic acid injection in rats. methods: the study rats were randomly assigned to three groups of sham, ka (ka was injected into the right side of the hippocampus) and ka+ra (a dose of 10 mg/kg/day through a gavage needle for one week before ka injection). then, histopathological changes, including apoptosis [terminal deoxynucleotidyl transferase (tdt) dutp nick-end labeling (tunel) assay], nnos-positive neurons number, as well as cox-2 and mapk immunoreactivity were evaluated in the hippocampus. results: in the ra pretreated group, nnos-positive neurons and tunel- positive cells were significantly reduced compared to the ka group (p<0.05). cox-2and mapk immunoreactivity demonstrated no significant changes compared to the ka group. they indicated a significant higher reactivity for cox-2 (p<0.01) and mapk (p<0.005) versus the sham group. conclusion: ra had neuroprotective effects, compared to ka, through reduced apoptosis and nnos-positive neurons, but not mapk and cox-2.