MEDIUM-TERM AND LONG-TERM EFFECTS OF REPEATED BICUCULLINE-INDUCED SEIZURES IN DEVELOPING RATS ON LOCAL CEREBRAL ENERGY-METABOLISM

To assess long-term metabolic consequences of recurrent ictal events a rising during development, seizures were repeatedly generated in rats at different stages of cerebral maturation. Seizures were induced by i .p. injections of bicuculline for three consecutive days, starting fro m postnatal day 5 (P5), when the brain is very immature, or from P15, a period at which the brain is more structurally organized. Local cere bral metabolic rates for glucose were measured in 74 structures ar P15 , P25 and in adults (P60), by the autoradiographic method using 2-D-[C -14]deoxyglucose. Repeated seizures in P5 to P7 pups led to a reductio n (16-34%) of glucose consumption at P15, mainly significant in sensor y, motor and functionally non-specific areas as well as in cerebellar nuclei. Selective decreases in metabolic activity were still recorded in adults, mostly in auditory system (20%) and cerebellar nuclei (27%) . Seizures generated from P15 to P17 led to an overall mortality rate of 62% (versus 22% at P5 to P7). Surviving animals exhibited reduced m etabolic rates for glucose (by 7-27%) at P25, significant in 23 struct ures, and depicting pronounced changes in Limbic, hypothalamic, sensor y and white matter areas, whereas brain functional activity finally re turned to basal values at P60. Therefore, while younger rats seemed to better tolerate repeated bicuculline-induced seizures than older anim als, the reverse was true for long-term metabolic effects, and the mor e immature the brain when seizures arise, the more persistent the func tional consequences. (C) 1998 Elsevier Science B.V. All rights reserve d.