Ž . Developmental Brain Research 98 1997 60–64 Research report GABA metabolism during status epilepticus in the developing rat brain Raman Sankar a,b,c, ) , Don H. Shin a,b,c , Claude G. Wasterlain a,c a Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA b Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA c Epilepsy Research Laboratories, Veterans Affairs Medical Center, SepulÕeda, CA, , USA Accepted 27 August 1996 Abstract The rate of synthesis of GABA, the major inhibitory neurotransmitter, was determined in parietal cortex and hippocampus during SE Ž . Ž . induced by systemic administration of lithium 3 mEqrkg followed 20 h later by pilocarpine 100 mgrkg in 1–4-week-old rats. Our results show that the immature hippocampus is better capable of maintaining GABA synthesis in the face of SE at the earliest stages of Ž . development studied 74.1% of basal in 1-week-old and that development results in a progressive decline of the ability to maintain Ž . GABA synthesis in the face of SE 44.1% of basal by 4 weeks that may parallel the ontogeny of self-sustaining seizures. Our data describe an aspect of developmental GABA neurochemistry which may in part explain the relative resistance of the immature hippocampus to seizure spread and of certain types of seizure-induced damage. Keywords: Status epilepticus; Pilocarpine; g-Aminobutyric acid; Hippocampus; Cortex 1. Introduction The developing brain has a greater tendency to undergo Ž . w x status epilepticus SE than the mature brain 1,5,15,22,24 . On the other hand, seizures tend to remain more localized and do not readily become self-sustaining in the immature brain. The immature brain also appears to be capable of withstanding SE without sustaining an adult-like pattern of hippocampal cell loss and mossy fiber sprouting in several experimental models of SE such as that induced by pilo- wx Ž . w x carpine 5 , systemic kainic acid KA 20 , or flurothyl w x 19 . On the other hand, hippocampal damage is demon- strable in a model of SE that involves stimulation of the w x wx perforant path in rats 25 and following kainate 9 or w x lithium-pilocarpine SE 26 in 10-day-old rabbits. The ontogeny of excitatory and inhibitory neurotrans- mitter systems in different regions of the brain may play an important role in this selective response of the develop- ing hippocampus to SE-induced changes. g-Aminobutyric Ž . acid GABA is the most abundant inhibitory neurotrans- mitter in the brain, and plays a crucial role in the initiation ) Ž . Corresponding author. Pediatric Neurology 22-474 MDCC , Box 951752, UCLA School of Medicine, Los Angeles, CA 90095-1752, USA. Ž.Ž . Fax: 1 310 825-5834; E-mail: rsankar@ucla.edu w x and termination of seizures. Both prenatal 12 and postna- wx tal 6 ontogeny of the GABAergic system have been described. The synthesis of GABA in various regions of the adult rat brain in response to SE has been studied by w x several methods 13,27,28 . However, regional GABA syn- thesis in the face of SE has not been studied in developing rats. We report the ability of the developing rat parietal cortex and hippocampus to maintain GABA synthesis in Ž . the face of lithium Li -pilocarpine-induced SE. Our re- sults show a distinctive aspect of the ontogeny of GABA neurochemistry in the regions studied, and may, in part, explain the tendency of the SE to remain localized and the seeming resistance of the developing hippocampus to seizure-induced changes in certain models of SE. 2. Materials and methods Wistar rat pups of postnatal age 1, 2, 3, and 4 weeks Ž . 4–6 animals per group were given 3 mEqrkg lithium Ž . Ž . chloride Sigma, St. Louis, MO intraperitoneally i.p. dissolved in deionized water 18–20 h prior to the experi- ment. Pups aged 2–4 weeks were anesthetized with a Ž mixture of ketamine and xylazine 60 and 15 mgrkg i.p., . respectively . They were placed on a stereotaxic instru- Ž . ment Stoelting, Wood Dale, IL and the skull was ex- 0165-3806r97r$17.00 Copyright q 1997 Elsevier Science B.V. All rights reserved. Ž . PII S0165-3806 96 00165-4