Memantine decreases neuronal degeneration in young rats submitted to LiCl-pilocarpine-induced status epilepticus

作者：Zenki Kamila Cagliari^*; Kalinine Eduardo; Zimmer Eduardo R; dos Santos Thaina Garbino; Marins Mussulini Ben Hur; Cruz Portela Luis Valmor; de Oliveira Diogo Losch^*

来源：NeuroToxicology, 2018, 66: 45-52.

DOI：10.1016/j.neuro.2018.03.005

• Status epilepticus
• Neuronal death
• Excitotoxicity
• Neuroprotection
• Memantine

Several works have demonstrated that status epilepticus (SE) induced-neurodegeneration appears to involve an overactivation of N-methyl-D-aspartate receptors and treatment with high-affinity NMDAR antagonists is neuroprotective against this brain damage. However, these compounds display undesirable side effects for patients since they block physiological NMDA receptor dependent-activity. In this context, memantine (MN), a well tolerable low-affinity NMDAR channel blocker, will be a promising alternative, since it does not compromise the physiological role of NMDA receptors on synaptic transmission. The aim of the present study was to investigate if MN could attenuate seizure severity and neuronal cell death caused by SE induced early in life. Wistar rats (15 days old; n = 6-8 per group) received memantine (20 mg/kg i.p.) in six different treatments: 6 and 3 h before SE onset; concomitant with pilocarpine; 15min and 1 h after SE onset; and four consecutive administrations (15 min, 6 h, 12 h, and 18 h) after pilocarpine injection. Neurodegeneration was quantified by fluoro-jade C staining. Treatment with memantine increase latency to SE onset only in groups treated 3 h before or concomitant with pilocarpine. In CA1 hippocampal subfield, memantine significantly reduced neurodegeneration at the following times: 3 h prior SE-onset, concomitant with pilocarpine, and 15 min after pilocarpine injection. For amygdala and thalamus, all post-SE onset treatments were able to decrease neuro-degeneration. In conclusion, the present study showed that MN was neuroprotective against SE-induced neuronal death and this neuroprotection appears to be time- and region-dependent.

• 出版日期2018-5