Baraban Laboratory
spacer_alt
spacer_alt
 Lab Home
 Research
 People
 Publications
 Affiliations
Current Research Projects
 
Epileptogenesis in a Malformed Brain

Click image for more
Cortical malformations are increasingly recognized as a major cause of epilepsy. Although clinical studies suggest that dysplastic neurons (e.g., cells located within a malformation) have epileptogenic properties and surgical ablation of malformed brain regions is often effective in reducing seizure frequency little is presently known about how seizures develop in a malformed brain. On-going studies address two fundamental questions: (i) How do dysplastic neurons function and (ii) How do dysplastic cells communicate? To investigate these issues, we primarily use visualized patch-clamp electrophysiological techniques. Studies focus on a rat model featuring nodular heterotopia in hippocampus (MAM), a mouse knockout for Type-1 lissencephaly (Lis1-het), and tissue sections from patients with focal cortical dysplasia (FCD).
 
Because hippocampal heterotopic cells in the MAM model exhibit a cortical phenotype, we are specifically interested in factors controlling their embryonic and early postnatal migration. In collaboration with Samuel Pleasure (Department of Neurology, UCSF), we are using immunohistochemistry, in situ hybridization, and organotypic slice cultures to study the migration of these cells.
 
 
 
Epilepsy in Tuberous Sclerosis Complex

Click image for more
Seizures occur in nearly 90% of tuberous sclerosis (TSC) patients. Although TSC1 and TSC2 genes have been identified as a cause of TSC, how seizures are generated in a TSC brain is unknown. Using a mouse model featuring neuron-specific inactivation of TSC1 and knock-down of TSC genes in zebrafish , we are currently studying neuronal and synaptic function in these animals. Studies incorporate Western blot and immunohistochemical analysis of protein expression, patch-clamp electrophysiological techniques in vitro and in primary dissociated cell cultures.
 
 
 
Epilepsy Gene Discovery in Zebrafish

Click image for more
Cellular and genetic factors resulting in seizure susceptibility are fairly well established. However, virtually nothing is known concerning mechanisms of seizure resistance. We recently developed an acute seizure model in zebrafish larvae (Danio rerio). Seizures in zebrafish exhibit behavioral, electrophysiological and pharmacological characteristics that are remarkably similar to those observed in mammals. Using a forward-genetic screening strategy we isolated seven “seizure-resistant” mutants. Identification of genes that confer resistance in these mutants is currently underway. Full characterization of these mutants, and further development of zebrafish as a model for epilepsy research, will provide valuable insight into mechanisms that can be used to control (or perhaps prevent) seizures.
 
 
 
Progenitor Cell Grafting and Epilepsy

Click image for more
Transplantation of neuronal precursors into the CNS offers great promise for the treatment of neurological disease. Recent reports of multipotent neural stem or progenitor cells with ability to disperse and differentiate into neurons in adult CNS have further raised expectations that defective brain circuits can be repaired. Using transplanted progenitors from the embryonic medial ganglionic eminence (MGE) we are exploring the possibility that these cells will influence synaptic function in the host brain and reduce hyperexcitability associated with seizures. By transplanting MGE-derived cells into epileptic mice lacking interneuron sub-populations we can directly test the therapeutic potential of this approach.
 
Collaborators: Arturo Alvarez-Buylla and John Rubenstein (UCSF)
 
 
 Lab Home Research People Publications Affiliations Contact Us
 
Department of Neurological Surgery, 2006
 
UCSF UCSF Medical Center UCSF School of Medicine
spacer_alt
spacer_alt
spacer_alt