Project: Research project

Project Details


Our understanding of epileptogenesis in the immature system is still quite
limited, especially since the mechanisms that determine excitability of
immature brain are likely to be different from those studied in mature CNS.
The current proposal will examine cellular processes resulting from
epileptogenic insults in the immature brain. Electrical stimulation,
hyperthermia, and hypoxia will be used to trigger abnormalities in the
hippocampal region of rat pups. Electrophysiological, morphological, and
imaging techniques will be used to characterize the patterns of cellular
abnormality arising from these insults. Field potential, intracellular,
and whole-cell patch recordings will be obtained from identified neurons in
thick and thin slices, and slice cultures of hippocampus. Extended
hippocampal slices, including entorhinal cortex, will also be analyzed in
an attempt to determine pathways of spread of excitability. Supplementing
the traditional electrophysiological and morphological/immunocytochemical
approaches will be two imaging techniques. Determinations of intracellular
calcium levels will be carried out in an attempt to correlate cell damage
with calcium fluxes resulting from traumatic injury. Voltage-sensitive
dyes will be used to supplement electrophysiological analysis of
excitability spread, especially in extended slices. Similar analyses will
be carried out at short time intervals after the epileptogenic treatment,
and at 3 and 6 months following treatment in order to determine whether
there are long-term effects of these insults. With these approaches, we
hope to be able to: a] determine the constellation of cellular parameters
that are altered by epileptogenic treatments, as a function of treatment,
age of the animal, and time after treatment; b] characterize the pattern of
spread of excitability in immature brain; c] examine the correlation
between intracellular rises in calcium and long-term functional and
structural abnormalities; and d] correlate morphological/immunocytochemical
damage with electrophysiological abnormalities. This information should
provide insight into the special features of immature brain that influence
its peculiar seizure susceptibility, and yield information about long-term
changes resulting from immature seizure episodes that may render the adult
brain more seizure-prone.
Effective start/end date8/1/783/31/95


  • National Institutes of Health: $231,297.00
  • National Institutes of Health: $129,806.00
  • National Institutes of Health: $239,636.00


  • Medicine(all)
  • Neuroscience(all)


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