Structural substrates of epilepsy.

Abstract

Although interest in possible structural substrates of epilepsy has been high since anatomical abnormalities in autopsy material were first noted, a clear pathognomic picture has yet to emerge for subtypes other than temporal lobe epilepsy. While identification of anatomical features unique to the diseased brain does not ensure that a cure will be found (viz. Alzheimer's disease), such knowledge can certainly guide researchers who must search out both the necessary and sufficient etiologic agent. Such investigation is hampered by the difficulty of separating cause from effect in clinical material, where the patient may have a history of drug use or of poorly controlled seizures. For instance, the cell-density depletion noted in temporal-lobe epileptics could follow from, or be a cause of, seizures. An experimental approach to isolating the structural substrates of epilepsy requires establishing several "levels" of epilepsy of varying duration, and observing the evolution of anatomical change. Such manipulation is, of course, possible only when an animal model is used, and it is for this reason, among others, that researchers have developed several of these. In general, there are two types of animal model: one where an exogenous agent (for example, a neurotoxin) or treatment (kindling) is applied, and another that relies on a strain of animal bred to exhibit seizures. Anatomical findings in this latter case have been reported infrequently, although the approach, which is not confounded by central nervous system (CNS) damage, seems promising as a model for certain types of epilepsy. Rodents have been among the best-researched genetic preparations, and several such reports appear in this volume. We have investigated one such strain, the Mongolian gerbil, which has been bred in UCLA's animal colony to exhibit seizures (the SS strain). Another strain (SR) has been bred to be seizure-free. Our initial study compared adult SS and SR animals with respect to two morphometric parameters in hippocampal region CA3. We found that the SS adult gerbil had fewer dendritic spines than its nonseizuring counterpart. Dendritic spines are considered the locus of excitatory synapses, and their density has been correlated with a variety of functional states in other paradigms. Our next set of questions concerned the development of these strain differences, and we accordingly set up four different age groups, bracketing the age at which seizures first appear in the gerbil. Again, spine-density differences appeared between SS and SR animals, but in the opposite direction from the adult case.(ABSTRACT TRUNCATED AT 400 WORDS)