OPIOID IN RNAS AND SEROTONERGIC RECEPTORS IN HIPPOCAMPUS OF EPILEPTIC PATIENTS

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Very few studies have examined brain chemistry in hippocampi of patients with intractable epilepsy. This is due in part to the difficulty in obtaining fresh brain samples that are suitable for these types of studies. The interdisciplinary approach to this research project makes it quite unique. The research team consists of a neurosurgeon (Dr. Inserni) who is interested in basic research, a neuroendocrinologist (Dr. Segarra) with expertise in receptor binding, radioimmunoassay and image analysis and a biochemical neuroscientist (Dr. Angulo) with expertise in the technique of in situ hybridization, image analysis and receptor binding. This study will examine brain tissue, specifically hippocampus, excised from patients with intractable complex partial seizures of temporal lobe origin. The serotonergic and opiate systems will be studied by in situ hybridization and receptor autoradiography to determine if these systems are involved in the etiology of temporal lobe epilepsy in patients with medically intractable seizures. Objective: This study will provide basic knowledge on the serotonergic and opiate system of human hippocampus. In addition, it will Compare the hippocampus of epileptic vs non-epileptic patients to determine if changes in the hippocampal endogenous opiate and serotonergic systems are implicated in the etiology of temporal lobe epilepsy in patients with medically intractable seizures. Specific Aims: (l) To determine the sites of endogenous opiate synthesis (enkephalins and dynorphins) in human hippocampi. (2) To investigate if patients with intractable complex partial seizures of temporal lobe origin exhibit permanent changes in the levels of endogenous opiates. (3) To determine the distribution and density of serotonergic 1A and 1B receptor subtypes in the hippocampi of human brains. (4) To investigate if complex partial seizures of temporal lobe origin in humans is associated with changes in hippocampal serotonergic receptor density. (5) To determine if changes in endogenous opiates levels or serotonergic receptor density is correlated with the degree of hippocampal sclerosis in patients with intractable complex partial seizures of temporal lobe origin.