The overall objective of this project is to achieve a better understanding of regional brain metabolism and blood flow in epilepsy. The techniques used are the (14-C)-2-deoxyglucose and (14-C)-iodoantipyrine quantitative autoradiographic methods in animals, and the (18-F)-fluorodeoxyglucose (FDG) method with positron emission tomography (PET) in humans. The two sections of this proposal are designed to complement each other. The first portion proposes the use of FDG-PET to determine cerebral glucose metabolic rate in three categories of childhood epilepsy: Lennox-Gastaut syndrome, infantile spasms and neonatal seizures. The metabolic patterns obtained through PET will be used to assess the involvment of different brain regions in these epilepsies in order to characterize various subgroups. Subsequently, the metabolic patterns will be related to certain clinical variables, such as specific seizure type, etiology and prognosis. The information so gained will result not only in a better understanding of childhood epilepsy, but also improved management of these patients. The second section of the proposal employs animal models to address several important issues in epilepsy, that for practical reasons, are best studied in the laboratory. Two general hypotheses are presented, based on our previous work. The first hypothesis states that the phenomenon of uncoupling between hippocampal blood flow and metabolism (decreased blood flow in the presence of increased glucose consumption) during seizures may partially account for human hippocampal sclerosis. Experiments are designed to study the uncoupling phenomenon in the ictal, postical and interictal periods. Pharmacological manipulation of this phenomenon will be attempted with naloxone and physostigmine. The second hypothesis centers on the role of endogenous opioids in epilepsy. It is postulated that opioids may at least partially mediate the uncoupling phenomenon. Experiments designed to study the effects of an opioid and opioid antagonist on kindled seizures, as well as studies to achieve an animal model of hippocampal sclerosis through multiple opioid infusions which would produce repeated hippocampal hypoperfusion, are proposed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07NS000886-05
Application #
3078268
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1984-07-01
Project End
1989-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Hovda, D A; Chugani, H T; Villablanca, J R et al. (1992) Maturation of cerebral oxidative metabolism in the cat: a cytochrome oxidase histochemistry study. J Cereb Blood Flow Metab 12:1039-48
Chugani, H T; Hovda, D A; Villablanca, J R et al. (1991) Metabolic maturation of the brain: a study of local cerebral glucose utilization in the developing cat. J Cereb Blood Flow Metab 11:35-47
Kerrigan, J F; Chugani, H T; Phelps, M E (1991) Regional cerebral glucose metabolism in clinical subtypes of cerebral palsy. Pediatr Neurol 7:415-25
Chugani, H T; Shields, W D; Shewmon, D A et al. (1990) Infantile spasms: I. PET identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment. Ann Neurol 27:406-13
Olson, D M; Chugani, H T; Shewmon, D A et al. (1990) Electrocorticographic confirmation of focal positron emission tomographic abnormalities in children with intractable epilepsy. Epilepsia 31:731-9
Chugani, H T; Mazziotta, J C; Phelps, M E (1989) Sturge-Weber syndrome: a study of cerebral glucose utilization with positron emission tomography. J Pediatr 114:244-53
Chugani, H T; Shewmon, D A; Peacock, W J et al. (1988) Surgical treatment of intractable neonatal-onset seizures: the role of positron emission tomography. Neurology 38:1178-88
Chugani, H T; Phelps, M E; Mazziotta, J C (1987) Positron emission tomography study of human brain functional development. Ann Neurol 22:487-97