CHEMOCONVULSANT SEIZURES - ADVANTAGES OF FOCALLY-EVOKED SEIZURE MODELS

Studies of short and long-term changes in regional metabolism, blood flow, gene expression (including immediate early genes and genes for neurotrophic factors), sprouting and cell death following seizures are pivotal to an understanding of the neural networks responsible for the generation of seizures. At the same time, this information forms a basis for understanding the pathophysiology associated with chronic, recurrent seizures. Systemic chemoconvulsant seizure models, produced by systemically administered chemoconvulsant agents, although convenient, are plagued with difficulties which confound the interpretation of their effects on the nervous system. These difficulties include. widespread direct cellular and physiological effects of the chemoconvulsant drugs, most of which are independent of seizures. In addition, numerous physiological changes occur as a secondary consequence of, or ancillary to, seizures, and it can be especially difficult to separate these effects from the direct effects of the propagated seizure discharge itself. Some of these difficulties can be overcome by the use of focally-evoked seizure models. Such models avoid the diffuse presence of drug throughout the CNS and thereby eliminate most of the direct cellular and physiologic actions of the drug apart from seizure-induction. Large regions of the brain distant from the focal site of drug application then can be examined for molecular, structural and physiologic changes uncomplicated by the presence of drug. Moreover, different focal sites of drug application can be compared to evaluate the specificity of the molecular changes to the neural network engaged in the seizure discharge. For example, limbic seizures, evoked by chemoconvulsant application into area tempestas, can be compared with brainstem convulsions evoked by chemoconvulsant application into inferior colliculus. Studies using focal drug application have also been successful in producing distant damage following status epilepticus and in demonstrating ''distant neuroprotection''. The importance of identifying seizure-specific pathophysiological alterations is discussed in the context of focal vs. systemic chemoconvulsant seizure models.