RADIATION-CONTROLLED FOCAL PHARMACOLOGY FOR EPILEPSY

  • Remler, Michael P (PI)

Project: Research project

Project Details

Description

The central goal of this work is the development of Radiation-controlled
Focal Brain Pharmacology, a technique to concentrate a neuropharmacologic
agent in a specific area of the brain without surgery. Irradiation of a
selected portion of the brain lowers the blood brain barrier (BBB) only in
that region. Consequently a drug that does not normally cross the BBB when
administered systemically will preferentially penetrate the selected region
of the brain. A specific application of the method has been the
development of the BBB-epileptogen Model of epilepsy. Following the focal
radiation lesion of the BBB, the administration of a systemic convulsant
results in focal seizure activity. Recurrent administration of the
systemic epileptogen can establish a chronic epileptic focus. With the BBB is open focally, epileptogenesis will be obtained using
continuous drug infusion. This provides a method for the evaluation of the
epileptogenic potential of a variety of systemically administered
chemicals. Significant synergistic or blocking interactions between drugs
in epileptogenesis can be explored. Excitatory drugs should be capable of
producing superior models of epilepsy and other drugs capable of blocking
epileptogenesis, that is preventing epilepsy. The BBB-epileptogen Model allows the epileptic focus to be established
anywhere in the brain. The location of the foci will be documented by
direct recording. The pattern of which drugs are most effective against
which locations of the focus should establish a correlation between focus
location and type of epilepsy and further validate the BBB-epileptogen
Model. During all of the above work Radiation-controlled Focal Brain
Pharmacology will be refined by the utilization of progressively lower
doses of radiation and lower drug levels. With lower doses of radiation, the application of Radiation-controlled
Focal Brain Pharmacology to the treatment of epilepsy can be developed.
Epileptic foci will be radiated to open the BBB. With the BBB open
focally, drugs with strong anticonvulsant properties on direct application
to an epileptic focus but that do not cross the normal BBB, will become
effective anticonvulsants when administered systemically, permeating the
epileptic focus but not other parts of the brain.
StatusFinished
Effective start/end date8/1/867/31/90

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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