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Numerous studies have examined the brain regional distribution of the immediate early gene (IEG), c-fos, following seizures induced by a variety of chemical or electrical provocations in the rat. Very little is known concerning the regional and temporal distribution of IEG expression following seizures in mice, and even less regarding the effects of development. In the present study, seizures of varying severities were induced in immature (postnatal day 17-18) and mature male (postnatal day 55-60) C3H mice with flurothyl, a volatile convulsant. In the immature mouse, neither c-fos nor c-jun mRNA were statistically elevated following any type of acute seizure activity. In the mature mouse, seizures of different severity resulted in differential effects on regional c-fos and c-jun mRNA expression. We conclude that the c-fos and c-jun are not reliable indicators of seizure activity in immature mice, whereas they remain indirect markers of neuronal activity in mature mice., (Copyright 2002 S. Karger AG, Basel)

Ketogenic diet (KD) is a high fat, low carbohydrate diet used to treat children with epilepsy that are refractory to conventional antiepileptic drugs (AEDs). The anticonvulsant mechanism of the KD is unknown. To determine if the noradrenergic system has a role in mediating the anticonvulsant action of the KD, dopamine beta-hydroxylase knockout (Dbh -/-) mice that lack norepinephrine (NE) and Dbh +/- littermates that have normal NE content were fed either a standard rodent chow or the KD. When exposed to the convulsant flurothyl, Dbh +/- mice fed the KD had significantly longer latencies to myoclonic jerk (MJ) and generalized clonic-tonic (CT) seizures than Dbh +/- mice fed normal chow. In contrast, Dbh -/- mice fed the KD had seizure latencies to both MJ and CT comparable to Dbh -/- mice fed normal chow. These results suggest that an intact, functional noradrenergic nervous system is required for the KD to exert an anticonvulsant effect.

Neurotransmitter receptors are critical elements in intercellular signaling within the central nervous system and are divided into two major types based on their molecular structure and biophysical properties. The first are ionotropic receptors--ligand-gated ion channels that directly affect the membrane potential via passage of permeant ions (such as sodium and calcium) and mediate fast synaptic transmission. The second type are slower metabotropic receptors that are also ligand gated but depend on an interaction with guanine nucleotide-binding proteins and mediate signal transduction by activating second-messenger systems within the cell. In the past two decades, a wealth of information has emerged regarding the molecular biology and pharmacology of classic neurotransmitter receptors (including adrenergic, dopaminergic, serotonergic, cholinergic, glycine, gamma-aminobutyric acid [GABA(A)], and glutamate receptors). Further, the distribution of subunits comprising these receptors has been extensively studied. This review focuses on the molecular ontogeny of several of the major neurotransmitter receptor systems in the mammalian central nervous system, highlighting the role that some of these may play during brain development and in certain pathologic states.

Background: Early childhood convulsions have been correlated with the finding of subsequent hippocampal neuronal loss and memory impairment in patients with intractable temporal lobe epilepsy. There is little direct evidence, however, that links early seizures with the later development of epilepsy and selective hippocampal neuronal loss., Objective: To study the long-term effect of early seizures on later seizure-induced neuronal damage and behavior., Methods: We used a "two hit" rat seizure mode in which systemic kainate was used to induce seizures during the second week of life (P15) and again in adulthood (P45). Memory was subsequently tested using a Morris water maze, and brains were examined for histologic evidence of injury., Results: Although the first kainate-induced seizure is not associated with detectable injury or cell death, it predisposes animals to more extensive neuronal injury after kainate-induced seizures in adulthood. Moreover, although early-life kainate-induced seizures cause no impairment of spatial learning, animals that have early-life and adult kainate-induced seizures perform significantly worse than those that have seizures only as adults., Conclusions: We concluded that early-life seizures, without causing overt cellular injury, predispose the brain to the damaging effect of seizures later in life.