, 1998). SE-induced nerve cell damage was considered to occur through both necrosis and apoptosis, whereas eosinophilic cells and nuclear fragmentation

in TUNEL staining was observed in SE-submitted animals (Kubova et al., 2004 and Sankar et al., 1998). In addition to the acute neuronal death, early life-induced SE can cause long-standing structural and functional changes in the brain. Cyclopamine datasheet Young rats (until 3 weeks old) submitted to SE presented a severe memory impairment in several tasks such as inhibitory avoidance and water maze at adulthood (de Oliveira et al., 2008, Hoffmann et al., 2004 and Sayin et al., 2004). Moreover, animals also displayed alterations in their emotional behavior, which was characterized by higher Selleckchem Fulvestrant levels of anxiety when exposed to the light–dark box and elevated plus maze (de Oliveira et al., 2008 and Sayin et al., 2004). SE-induced neuronal degeneration has been frequently associated with an excessive activation of NMDA ionotropic glutamate receptors (NMDAR) (Holopainen, 2008) and previous studies have demonstrated that pretreatment with NMDAR antagonists is neuroprotective against SE-induced neuronal death (Clifford et al., 1990, Fujikawa, 1995 and Holmes, 2004). However, despite the treatment of patients with SE started after onset of seizures, there are no studies investigating the effects of NMDAR blockage during SE. Thus, it becomes important to know the effectiveness of post-SE Cyclin-dependent kinase 3 onset treatments

with NMDAR antagonists in order to avoid the short- and long-lasting alterations induced by SE. Therefore, the aim of this study was to investigate the putative protective action of a post-SE onset treatment with ketamine, a non-competitive NMDAR antagonist, on SE-induced neuronal death as well as on long-term behavioral alterations in animals submitted to SE early in life. The convulsive pattern presented by LiCl–pilocarpine-treated

animals was similar to that described by de Oliveira et al. (2008). Systemic administration of LiCl–pilocarpine produced defecation, salivation, body tremor, and scratching within 2 to 8 min. This behavioral pattern progressed within 8 to 13 min to increased levels of motor activity and culminated in SE in all animals. SE was characterized by sustained orofacial automatisms, salivation, chewing, forelimb clonus, loss of righting reflex and falling. Animals treated with ketamine after SE onset presented a distinct behavioral pattern of seizures when compared with LiCl–pilocarpine rats. Five minutes after antagonist administration, both groups that received ketamine at 15 min (SE+KET15) or at 60 min (SE+KET60) showed a reduction in the intensity of sustained orofacial automatisms, forelimbs clonus and chewing, without recovery of the loss of righting reflex. The SE-induced motor activity was stopped only 70 min after SE onset for both ketamine-treated groups. Ketamine when administered at doses higher than 45 mg/kg, caused death in all SE-induced animals (data not shown).