AGE RELATED SEIZURE SUPPRESSION

Project: Research project

Description

The objective of this proposal is to identify mechanisms involved in the
suppression of seizures as a function of age. Ongoing studies suggest that
the increased seizure susceptibility of the immature brain may be due to
age-specific differences in the GABAA receptor subtypes within the
substantia nigra (SN), a site that is crucial for the control of seizures
in adults. The aims are to determine 1) whether there are differences in
nigral GABAA receptor isoforms as a function of age; 2) whether there is a
different functional role of nigral GABAA receptor isoforms on seizures as
a function of age and drug dosage; 3) the nigral GABAA sensitive output
systems involved in the modification of seizures as a function of age, drug
and dose. Methods include in vitro studies (in situ hybridization
histochemistry) to determine the ontogeny of particular GABAA isoforms; in
vivo studies to determine the seizure susceptibility of rats of various
ages after intracranial microinfusions of relatively specific GABAA agents
in the SN via chronic indwelling cannulae in the flurothyl model of
epilepsy; and deoxyglucose autoradiographic studies to map the nigral
efferents activated by the relatively specific GABAA agents. Rats of
various ages throughout development will be used to determine the
maturational profile of the SN-mediated seizure modification. The goal is
to develop a better understanding of the mechanisms that participate in the
suppression of seizures with maturation. These studies may lead to the
development of new therapeutic treatments that will compensate for the
maturational state of the CNS.
StatusFinished
Effective start/end date9/30/848/31/13

Funding

  • National Institutes of Health: $505,592.00
  • National Institutes of Health: $340,319.00
  • National Institutes of Health: $365,836.00
  • National Institutes of Health: $177,927.00
  • National Institutes of Health: $505,557.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $431,695.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $400,307.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $415,703.00
  • National Institutes of Health: $352,828.00
  • National Institutes of Health: $415,486.00
  • National Institutes of Health: $495,985.00
  • National Institutes of Health: $437,775.00
  • National Institutes of Health: $210,554.00
  • National Institutes of Health
  • National Institutes of Health: $315,185.00
  • National Institutes of Health
  • National Institutes of Health: $285,945.00
  • National Institutes of Health: $391,823.00
  • National Institutes of Health
  • National Institutes of Health: $497,880.00

Fingerprint

Seizures
Substantia Nigra
Flurothyl
GABA-A Receptors
Deoxyglucose
Status Epilepticus
Testosterone
Anticonvulsants
Autoradiography
gamma-Aminobutyric Acid
Brain
GABAergic Neurons
Efferent Pathways
Immunohistochemistry
Epilepsy
GABA Receptors
Protein Isoforms
Therapeutics
Pars Reticulata
GABA Agents

ASJC

  • Medicine(all)
  • Neuroscience(all)