SUNY Downstate Medical Center
Department of Physiology and Pharmacology
Jeffrey H. Goodman, PhD
Physiology and Pharmacology
Tel: (718) 494-5148
Development of new therapies for epilepsy using in vivo experimental seizure models
The lab focuses on the development of deep brain electrical stimulation as a new therapy for epilepsy; the development of neuroprotective agents that limit the damage associated with traumatic brain injury and the development of post traumatic epilepsy; the effect of developmental hypothyroidism on brain development.
A significant number of patients with epilepsy are unresponsive to pharmacologic therapy or are not candidates for surgical intervention. This highlights the need for a better understanding of the abnormal circuitry underlying the development of epilepsy and the need for new therapies with no side effects. Deep brain electrical stimulation is a candidate therapy being investigated in the laboratory.
Experimental in vivo models including kindling, tetanus toxin, and pilocarpine and kainic acid-induced status epilepticus are used to generate rodents that spontaneously seize. Stereotaxic surgery is performed to implant chronic recording electrodes that can detect electrographic seizure activity as well as provide a means for the delivery of therapeutic stimulation in an awake, freely-moving animal. Behavioral and electrographic seizure activity are detected using a 12-cage video/EEG monitoring unit. Histochemical and immunohistochemical techniques are combined with in vivo electrophysiology to provide a structural-functional assessment of efficacy and safety. Experimental models of epilepsy are also used to address questions related to the effect of seizures on cardiovascular function, seizure-induced cell death, synaptic reorganization and neurogenesis.
The Controlled Cortical Impact (CCI) model of traumatic brain injury (TBI) is used to identify biomarkers of the epileptogenic process that could be targets for therapeutic intervention and for testing potential neuroprotective/antiepileptogenic agents. Currently we are developing tissue clearing techniques to evaluate changes in blood brain barrier integrity after TBI in 3-dimension.
In collaboration with scientists at the EPA we discovered a cortical malformation, a subcortical band heterotopia, in the corpus callosum of rat pups born to dams that were mildly hypothyroid during gestation and lactation. The neurons within the heterotopia were anatomically and functionally connected with cortical neurons in both hemispheres. Although not directly correlated with the presence of the heterotopia these animals exhibited a reduced expression of parvalbumin and an increased susceptibility to seizures.
Research Scientist, Institute for Basic Research
Member of the Doctoral Faculty, Biology Program, City University of New York (CUNY)
Member of the Board of Directors – Research Foundation for Mental Hygiene of NY
Chair Governance Committee
Member, Editorial Board Epilepsia
Member, DoD CDMRP, Epilepsy Research Program Integration Panel (2015-2018)
- Goodman, J. H., Homan, R., and Crawford, I. (1990). Kindled Seizures Elevate Blood Pressure and Induce Cardiac Arrhythmias. Epilepsia 31, 489-495.
- Sloviter, R. S., Dean, E., Sollas, A., and Goodman, J. (1996). Apoptosis and necrosis induced in different hippocampal neuron populations by repetitive afferent stimulation in the rat. J. Comp. Neurol. 366, 516-533.
- Sloviter, R. S., Dichter, M., Rachinsky, T., Dean, E., Goodman, J., Sollas, A., and Martin, D. (1996). Basal expression and induction of glutamate decarboxylase and GABA in excitatory granule cells of the rat and monkey hippocampal dentate gyrus. J. Comp. Neurol. 373, 1-26.
- Scharfman, H. E., Goodman, J., and Sollas, A. (2000). A network of granule-like neurons at the CA3/Hilar border of the hippocampus after chronic seizures. J. Neurosci. 20, 6144-6158.
- Scharfman, H. E., Sollas, A., and Goodman, J. (2002). Spontaneous limbic seizures after pilocarpine-induced status epilepticus activate newly born granule cells in the hilus of the rat dentate gyrus. Neuroscience 111, 71-81.
- Goodman, J. H., Berger, R., and Tcheng, T. (2005). Preemptive low frequency stimulation decreases the incidence of amygdala kindled seizures. Epilepsia 46, 1-7.
- Goodman, J. H. and Gilbert, M. (2007). Modest thyroid hormone insufficiency during development induces a cellular malformation in the corpus callosum of the rat: A model of cortical dysplasia. Endocrinology 148, 2593-2597.
- Gilbert, M. E., Ramos, R., McCloskey, D., Goodman, J. (2014). Subcortical band heterotopia (SBH) in rat offspring following maternal hypothyroxinemia: Structural and functional characteristics. Journal of Neuroendocrinology 26, 528-541.
Complete List of Published Work in MyBibliography: