KB-R7943 reduces 4-aminopyridine-induced epileptiform activity in adult rats after neuronal damage induced by neonatal monosodium glutamate treatment

Background: neonatal monosodium glutamate (msg) treatment triggers excitotoxicity and induces a degenerative process that affects several brain regions in a way that could lead to epileptogenesis. na+/ca2+ exchangers (ncx1-3) are implicated in ca2+ brain homeostasis; normally,they extrude ca2+ to control cell inflammation,but after damage and in epilepsy,they introduce ca2+ by acting in the reverse mode,amplifying the damage. changes in ncx3 expression in the hippocampus have been reported immediately after neonatal msg treatment. in this study,the expression level of ncx1-3 in the entorhinal cortex (ec) and hippocampus (hp); and the effects of blockade of ncxs on the seizures induced by 4-aminopyridine (4-ap) were analysed in adult rats after neonatal msg treatment. kb-r7943 was applied as ncxs blocker,but is more selective to ncx3 in reverse mode. methods: neonatal msg treatment was applied to newborn male rats at postnatal days (pd) 1,3,5,and 7 (4 g/kg of body weight,s.c.). western blot analysis was performed on total protein extracts from the ec and hp to estimate the expression level of ncx1-3 proteins in relative way to the expression of β-actin,as constitutive protein. electrographic activity of the ec and hp were acquired before and after intracerebroventricular (i.c.v.) infusion of 4-ap (3 nmol) and kb-r7943 (62.5 pmol),alone or in combination. all experiments were performed at pd60. behavioural alterations were also recorder. results: neonatal msg treatment significantly increased the expression of ncx3 protein in both studied regions,and ncx1 protein only in the ec. the 4-ap-induced epileptiform activity was significantly higher in msg-treated rats than in controls,and kb-r7943 co-administered with 4-ap reduced the epileptiform activity in more prominent way in msg-treated rats than in controls. conclusions: the long-term effects of neonatal msg treatment include increases on functional expression of ncxs (mainly of ncx3) in the ec and hp,which seems to contribute to improve the control that kb-r7943 exerted on the seizures induced by 4-ap in adulthood. the results obtained here suggest that the blockade of ncxs could improve seizure control after an excitotoxic process; however,this must be better studied. © 2017 the author(s).