Objective: To study the long-term effect of flurothyl-induced recurrent seizures in neonatal rats on cognition, seizure susceptibility, and NMDA receptor expression in adult rat brain.
Methods: Seizures were induced by inhalant flurothyl for 6 days, starting from postnatal day 6 (P6). On P60, rats were tested for spatial memory by using the Morris water maze task. Seizure threshold was examined by intraperitoneal injection of pentylenetetrazol (PTZ) on P75. Brain homogenates were made at the same time. Expression of NMDA receptor protein in cerebral cortex and hippocampus was examined with Western blotting analysis.
Results: Compared with the control group, flurothyl-treated rats showed significant spatial deficits in the Morris water maze on P60. There was no difference in seizure threshold. In the cerebral cortex of flurothyl-treated rats, the protein expressions of NR1, NR2A, and NR2B decreased significantly, but NR2C increased significantly. In the hippocampus of flurothyltreated rats, the protein expression of NR2A decreased significantly, the protein expression of NR2C increased significantly, and NR1 and NR2B were similar to that in the hippocampus of control group.
Conclusion: Recurrent seizures in neonatal rats might cause long-term cognitive deficit and modify NMDA receptor subunit expressions in cerebral cortex and hippocampus of adult rats. This phenomenon raised the possibility that abnormal NMDA receptor expression might play an important role in long-term cognitive deficit induced by early life recurrent seizures.