HIPPOCAMPAL DAMAGE AS A CAUSE OF EPILEPSY

Project: Research project

Project Details

Description

Several patterns of hippocampal cell loss are observed in the
clinical population with focal epilepsy of temporal lobe origin. It
is generally agreed that seizures, with associated
ischemic/hypoxic distress, predate this hippocampal damage.
Once produced, however, there has been little work to determine
if this cell damage contributes to the progression of epilepsy. The
present proposal examines the acute and chronic physiologic,
morphologic and neurochemical consequences of these clinically
relevant lesions produced in both adult and developing rats. Lesions of hippocampal subfield CA3, or the "end blade", will be
produced by intraventricular kainic acid. Lesions of hippocampal
subfield CA1, or "Sommer's sector", will be produced by transient
forebrain ischemia. The development of epileptogenesis in
remaining neurons will be determined by in vivo subcortical
recording or in vitro recording in the hippocampal slice
preparation. Each treatment will be analyzed further to
determine contributing neuroplastic rearrangements in
hippocampus which may promote, or prevent, epileptogenesis.
The integrity of hippocampal inhibitory neurons and receptors for
GABA, will be determined by GAD immunocytochemistry and
quantitative in vitro autoradiography. Alterations in hippocampal
excitatory function will be determined by similar
immunocytochemical and autoradiographic methods examining
glutamate and its several post-synaptic receptor subtypes.
Specific hypotheses include: 1) lesions of CA3 will produce
epileptogenesis in adults, as has already been demonstrated; they
will not be epiletogenic when produced in neonates, primarily
because of a different pattern of reactive sprouting in
hippocampus; 2) loss of CA1 will be epileptogenic when produced
in both young and adult animals; young animals may be more
severely affected primarily due to extensive recurrent excitatory
collateral sprouting in remaining CA3 neurons; 3) epileptogenic
treatments will be accompanied by abnormal morphologic and
functional interactions between inhibitory and excitatory neurons
in the hippocampus and by specific changes in transmitter
immunoreactivity and receptors. The work proposed will provide a needed body of data on the
consequences of lesions frequently observed in human
hippocampus. It will further identify the age dependence of the
lesions sequelae. Such information could provide a foundation for
assessing the need for, and designing, interventive treatments in
the clinical population suffering from lesion producing trauma
and/or seizures.
StatusFinished
Effective start/end date4/1/883/31/94

Funding

  • National Institutes of Health: $100,703.00

ASJC

  • Medicine(all)
  • Neuroscience(all)

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