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Consequences of neonatal seizures in the rat: Morphological and behavioral effects
Author(s) -
Holmes Gergory L.,
Gairsa JeanLuc,
ChevassusAuLouis Nicolas,
BenAri Yehezkel
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410440602
Subject(s) - hippocampal formation , dentate gyrus , neurogenesis , granule cell , epilepsy , neuroscience , seizure threshold , hippocampus , convulsion , medicine , anesthesia , psychology , anticonvulsant
Whereas neonatal seizures are a predictor of adverse neurological outcome, there is controversy regarding whether seizures simply reflect an underlying brain injury or can cause damage. We subjected neonatal rats to a series of 25 brief flurothyl‐induced seizures. Once mature the rats were compared with control littermates for spatial learning and activity level. Short‐term effects of recurrent seizures on hippocampal excitation were assessed by using the intact hippocampus formal preparation and long‐term effects by assessing seizure threshold. Brains were analysed for neuronal loss, sprouting of granule cell axons (mossy fibers), and neurogenesis. Compared with controls, rats subjected to neonatal seizures had impaired learning and decreased activity levels. There were no differences in paired‐pulse excitation or inhibition or duration of afterdischarges in the intact hippocampal preparation. However, when studied as adults, rats with recurrent flurothyl seizures had a significantly lower seizure threshold to pentylenetrazol than controls. Rats with recurrent seizures had greater numbers of dentate granule cells and more newly formed granule cells than the controls. Rats with recurrent seizures also had sprouting of mossy fibers in CA3 and the supragranular region. Recurrent brief seizures during the neonatal period have long‐term detrimental effects on behavior, seizure susceptibility, and brain development.