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.
| Remler, M P; Marcussen, W H; Sigvardt, K (1989) Systemic carbachol used in radiation-controlled focal brain pharmacology can decrease rat running. Life Sci 45:151-6 |
| Remler, M P; Marcussen, W H (1986) Systemic focal epileptogenesis. Epilepsia 27:35-42 |
| Remler, M P; Marcussen, W H; Tiller-Borsich, J (1986) The late effects of radiation on the blood brain barrier. Int J Radiat Oncol Biol Phys 12:1965-9 |
| Remler, M P; Marcussen, W H (1985) Bicuculline methiodide in the blood-brain barrier-epileptogen model of epilepsy. Epilepsia 26:69-73 |
