Interictal spikes in developing rats cause long-standing cognitive deficits.
Frequent interictal spikes are a common finding in the electroencephalograms of children with epileptic encephalopathies. While it is well recognized that interictal spikes are a biological marker of seizures and can lead to transitory cognitive impairment, whether interictal spikes can result in long-standing adverse effects on learning and memory in children is not known. Here we investigated the consequences of interictal spikes in rat pups without seizures on long-term learning and memory. Rat pups were given a low dose of flurothyl for 4h for 10 days during continuous electroencephalographic monitoring. Rats developed interictal spikes without seizures while age-matched controls under similar testing conditions had few interictal spikes. When rats were tested as adults, there was impairment in reference memory in the probe test of the Morris water maze, reference memory impairment in the four-trial radial-arm water maze and impaired long-term potentiation. Early-life interictal spikes resulted in impaired new cell formation and decreased cell counts in the hippocampus but did not cause an increase in apoptosis. This study, for the first time demonstrates that interictal spikes in rat pups without seizures can result in long-standing spatial cognitive impairment. Our findings suggest that suppressing IIS may be as important as treating seizures during brain development.
Khan
Omar I
OI
Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire 03756, USA.
Zhao
Qian
Q
Miller
Forrest
F
Holmes
Gregory L
GL
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D003292:Convulsants / Q000494:pharmacology; D004567:Electrodes, Implanted; D004569:Electroencephalography; D005481:Flurothyl / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology
D003292:Convulsants; D005481:Flurothyl
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