Effect of cuprizone-induced demyelination on seizure susceptibility in immature rats

Abstract

Objective To evaluate the effect of cuprizone-induced demyelination on seizure susceptibility in immature rats. Methods Demyelination model was induced in 21 d immature rats fed with 0.6% cuprizone (CPZ) for 2 weeks (CPZ 2 weeks group) and 4 weeks (CPZ 4 weeks group).Morphological changes of myelinated fibers were examined using Gallyas staining.The expression of myelin basic protein (MBP) was determined by immunohistochemistry and western blot.The latency of seizure in CPZ rats induced by pilocarpine and the latency of spontaneous of discharge in hippocampus slices induced by Mg2+free artificial cerebrospinal fluid (ACSF) were determined.In addition，behavior and epileptiform spikes were recorded by video-electroencephalogram monitoring.The apoptosis cells in hippocampus of rats were detected by Td T-mediated dutp nick end labeling (TUNEL). Results The results showed that myelinated fibers of the CPZ group were degenerated，and with significantly decreased MBP expression，related to control group rats.Besides，the MBP expression was decreased significantly in CPZ 2 weeks group compared to that of rats in CPZ 4 weeks group.The latency of seizure induced by pilocarpine was decreased in CPZ 4 weeks group ((13.33±3.46) min) related to that in control group ((19.66±4.33) min，t=4.62，P<0.01).In addition，the latency induced by Mg2+free ACSF in hippocampus slice was significantly decreased in CPZ 2 weeks group ((35.00±5.03) min vs (49.86±10.65) min，t=3.34，P<0.05) and CPZ 4 weeks group ((19.29±3.95) min vs (51.86±10.78) min，t=7.50，P<0.01).While no spontaneous epileptiform spikes were observed in control group，abnormal discharge can be seen in 7/11 of CPZ 2 weeks rats and 10/10 of CPZ 4 weeks rats.Finally，there was no difference in the numbers of apoptosis cells in hippocampus between CPZ groups and control groups. Conclusions Immature rats treated with CPZ show increased seizure susceptibility which is strongly correlated with the severity of demyelination.Our study offers an insight that some relationship may be presentbetween demyelination and seizure. Key words: Demyelinating diseases; Seizures; Disease susceptibility; Disease models，animal; Rats，sprague-dawley