title: Ketamine reduces neuronal degeneration and anxiety levels when administered during early life-induced status epilepticus in rats.
abstract: Status epilepticus (SE) when occurred during brain development can cause short- and long-term consequences, which are frequently associated with NMDA-mediated glutamatergic excitotoxicity. In the present work, we investigated the putative neuroprotective role of ketamine, an NMDA receptor antagonist, on early life SE-induced acute neuronal death and long-term behavioral abnormalities. Male Wistar rats (16 postnatal days) were induced to SE by LiCl-pilocarpine i.p. administration (3 mEq/kg; 60 mg/kg, respectively). Fifteen or 60min after pilocarpine injection, animals received a ketamine administration (22.5mg/kg i.p.). Neuronal degeneration was assessed 24h after SE induction. Another subset of animals was destined to behavioral tasks in adulthood (75-80 postnatal days). Fluoro-Jade C labeling revealed a marked neuronal death on CA1 hippocampal subfield, habenula, thalamus and amygdala in SE animals. Ketamine post-SE onset treatment prevented neuronal death in all regions assessed. In the elevated plus maze, SE induced an increase in anxiety-like behaviors whereas ketamine administration during seizures was able to prevent this alteration. Ketamine administration in non-SE animals resulted in high anxiety levels. There were no observed differences among groups in the open field task in all parameters analyzed. Our results suggest that ketamine post-SE onset treatment was effective in preventing acute and long-standing alterations caused by SE early in life, which indicates a putative role of glutamatergic system on SE-induced brain damage as well as long-lasting behavioral consequences.
authors.affiliation: Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil. cassio.loss@ibest.com.br
authors.forename: Cássio Morais
authors.initials: CM
authors.lastname: Loss
authors.forename: Sandro Daniel
authors.initials: SD
authors.lastname: Córdova
authors.forename: Diogo Losch
authors.initials: DL
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D001007:Anxiety / Q000517:prevention & control*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003292:Convulsants / Q000633:toxicity; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology
chemical_list: D003292:Convulsants; D018696:Neuroprotective Agents; D010862:Pilocarpine; D007649:Ketamine