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 1h 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 neurodegeneration. 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.

几项研究表明，癫痫持续状态（SE）诱导的神经变性似乎涉及N-甲基-d的过度激活。-天冬氨酸受体和高亲和力NMDAR拮抗剂治疗对这种脑损伤具有神经保护作用。然而，这些化合物对患者显示出不良的副作用，因为它们阻断了生理性NMDA受体依赖性活性。在这种情况下，美金刚（MN）是一种耐受性良好的低亲和力NMDAR通道阻滞剂，将是一个有前途的替代方案，因为它不会损害NMDA受体在突触传递中的生理作用。本研究的目的是研究MN是否可以减轻SE引起的癫痫发作严重程度和神经元细胞死亡。Wistar大鼠（15天大；每组n = 6-8）在六种不同的治疗中接受美金刚（20 mg / kg ip ip）：SE发作前6和3 h；伴随毛果芸香碱；SE发作后15分钟和1小时；和四个连续的主管部门（15分钟，注射毛果芸香碱后6 h，12 h和18 h）。通过氟玉石C染色定量神经变性。美金刚治疗仅在毛果芸香碱治疗前3h或同时伴发毛果芸香碱会增加SE发作的潜伏期。在CA1海马亚区，美金刚在以下时间显着减少了神经变性：SE发作前3小时，伴毛发松果体和注射毛发松果体后15分钟。对于杏仁核和丘脑，所有SE发作后的治疗均能够减少神经变性。总之，本研究表明，MN对SE诱导的神经元死亡具有神经保护作用，而这种神经保护作用似乎是时间和区域依赖性的。美金刚治疗仅在毛果芸香碱治疗前3h或同时伴发毛果芸香碱会增加SE发作的潜伏期。在CA1海马亚区，美金刚在以下时间显着减少了神经变性：SE发作前3小时，伴毛发松果体和注射毛发松果体后15分钟。对于杏仁核和丘脑，所有SE发作后的治疗均能够减少神经变性。总之，本研究表明，MN对SE诱导的神经元死亡具有神经保护作用，而这种神经保护作用似乎是时间和区域依赖性的。美金刚治疗仅在毛果芸香碱治疗前3h或同时伴发毛果芸香碱会增加SE发作的潜伏期。在CA1海马亚区，美金刚在以下时间显着减少了神经变性：SE发作前3小时，伴毛发松果体和注射毛发松果体后15分钟。对于杏仁核和丘脑，所有SE发作后的治疗均能够减少神经变性。总之，本研究表明，MN对SE诱导的神经元死亡具有神经保护作用，而这种神经保护作用似乎是时间和区域依赖性的。所有的SE后发作治疗都能够减少神经退行性变。总之，本研究表明，MN对SE诱导的神经元死亡具有神经保护作用，而这种神经保护作用似乎是时间和区域依赖性的。所有的SE后发作治疗都能够减少神经退行性变。总之，本研究表明，MN对SE诱导的神经元死亡具有神经保护作用，而这种神经保护作用似乎是时间和区域依赖性的。