Libor Velisek

Many epileptic syndromes develop in the terrain of prenatally compromised brain. There are several "catastrophic epilepsies of childhood" including Early Infantile Encephalopathy, West Syndrome, and Lennox-Gastaut Syndrome that often arise in the terrain of pre- or perinatally damaged brain. These syndromes are further debilitating for the child's progress and have unfavorable prognosis. Studies are performed to determine the effects that prenatal insults may have on further development of the nervous system. Currently, several models of prenatal brain damage are under development including those induced by prenatal administration of methylazoxymethanol, methotrexate, corticosteroids and possibly, neurotrophins. Brain function is tested postnatally using a variety of available in vivo and in vitro tests such as reflex behavior, motor skills, learning and memory, and seizure susceptibility. Brain morphology is assessed using light and fluorescent microscopy, metabolic imaging studies and binding essays.

Extracellular glucose is an energetic substrate for neuronal function and it has also signaling features. In diabetic patients, seizures frequently occur as a complication of hypoglycemia (due to excessive physical activity, a missed meal or therapeutic overcompensation). However, in the in vitro environment with decreased extracellular glucose activity of neurons is gradually decreased. This differential effect may be due to differences in metabolic and signaling features of glucose or due to differences in reaction to hypoglycemia in differential brain structures (forebrain vs. brain stem). Studies are performed both in vivo in animal models and in vitro in brain slices to determine specific features of brain extracellular glucose and their mechanisms of action in the brain.

Stimulation of deep brain sites (subthalamic nucleus) is a novel interesting approach for treatment of refractory Parkinson's disease. There are also several pilot studies showing that rhythmical stimulation of various structures (such as caudate or cerebellum) may help the patients with refractory seizures. Our data show that the high-freqeuncy stimulation of either subthalamic nucleus or substantia nigra pars reticulata (see Dr. S.L. Moshé and Dr. J. Veliskova) has anticonvulsant effects in flurothyl-induced seizures in rats. The experiments are performed using long-term monitoring techniques to determine whether the stimulation of either subthalamic nucleus or substantia nigra pars reticulata is effective in the model of spontaneous seizures developing following the kainic acid administration.

Studies are performed both in vivo and in vitro, utilizing a variety of techniques including intracranial electrical and chemical stimulations, behavioral studies, EEG recordings, receptor binding assays, deoxyglucose autoradiography, in situ hybridization histochemistry and special anatomical staining techniques (including immunohistochemistry and immunofluorescence).

Students interested in brain function in normal and prenatally compromised brain can choose thesis projects utilizing any of the techniques we are currently using in the lab. Our general approach is to use the best suited technique for the questions asked.

Selected Publications