Epileptogenesis is increased in rats with neonatal isolation and early-life seizure and ameliorated by MK-801: a long-term MRI and histological study.
Early-life stress has been shown to destabilize the homeostatic synaptic plasticity and compromise the developing brain to the later encountered insults. This study would determine the long-term epileptogenic effect of neonatal isolation (NI) on early-life seizure. There were five groups: normal rearing (NR) rats; NI rats; NR rats suffering from status epilepticus (SE) at P12 (NR-SE); NI-SE rats; NI-SE-MK801 rats. All adult rats were video monitored to detect behavioral seizures, examined with brain magnetic resonance imaging, and assessed for hippocampal NeuN-immunoreactive (NeuN-IR) cells. Behavioral seizures were detected in one of six NR-SE rats, all the NI-SE rats (eight of eight), and none in the NR, NI, or NI-SE-MK801 rats. High hippocampal T2 signal were only found in three of five NR-SE rats, five of six NI-SE rats, and one of five NI-SE-MK801 rats. There was a significant decrease in the number of hippocampal NeuN-IR cells in the NR-SE and NI-SE groups, compared with the NR group, and MK-801 treatment ameliorated the neuronal loss. Our results demonstrated that NI led to an increase in epileptogenesis in rat pups with early-life SE, and treatment with MK-801 could ameliorate brain injuries, indicating a critical role of N-methyl-d-aspartic acid receptor in the epileptogenic process.
Lai
Ming-Chi
MC
Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan.
Lui
Chun-Chung
CC
Yang
San-Nan
SN
Wang
Jia-Yi
JY
Huang
Li-Tung
LT
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology; D012934:Social Isolation; D013226:Status Epilepticus / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology
D018696:Neuroprotective Agents; D016291:Dizocilpine Maleate