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The abdomen, the chest, and the brain will forever be shut from the intrusion of the wise and humane surgeon.

- Sir John Eric Ericksen, British surgeon, appointed Surgeon-Extraordinary to Queen Victoria, 1873







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epilepsy

Steven N. Roper, MD

department of neurosurgery

 
Read the proposal writter by Dr. Steven Roper for more information
what is cortical dysplasia?

Cortical dysplasia is one of the most common forms of intractable epilepsy found in children and adults. It is a congenital abnormality of the brain which results in failure of certain neuronal migrate during in utero development. Many times, this results in the marked presence of abnormal neurons, such as immature neurons, dysmorphic neurons, and giant neurons. The presence of these abnormal cells causes signaling malfunctions which result in epilepsy and chronic seizures. It is thought that networks of CD are hyperexcitable which then leads to initiation of seizures. Other abnormalities present include a reduction in the number of GABAerigic interneurons and reduced inhibitory activity in pyramidal cells.

 

 

 

Characteristics of dysplastic cortex. A. Photomicrographs of coronal sections of control (left) and dysplastic (right) cortex with cresyl violet staining. B. Photomicrographs (upper) show two biocytin-stained pyramidal cells from dysplastic cortex. Arrows point to pia. Traces (lower) show spike patterns of these two cells to depolarizing current injection (300 ms, 300 pA). From: Chen et al., 2006.
stem cell therapy

Adult human neural progenitor cells (AHNPs) provide a potential method to treat certain brain disorders by restoring a population of brain cells that has been lost or whose function is otherwise reduced. Many pathways in the brain consist of relatively long distance connections of neurons, so the most realistic scenario for potential neuron restoration would involve abnormalities of local connections.  Epilepsy, which involves an abnormality in local neuronal circuitry, is a promising candidate disease for AHNP therapy.  Cortical dysplasia (CD) is an abnormality of brain development that produces severe epilepsy in children and adults. In this project, I have been using AHNPs to help restore a certain type of brain cell in an animal model of cortical dysplasia. This model has been shown to have abnormal numbers of these brain cells in the hemispheres of the brain.  

The methodology involves implantation of human progenitor cells into rats with CD.  This involves using a Hamilton syringe to inject a known amount of AHNPs into the cortex of one-day old rat pups (their thin skulls at this age do not require a craniotomy to be performed).  The cortical dysplasia was produced in these pups because we exposed pregnant rats to gamma-radiation on the 17th day of gestation.  The AHNPs were obtained from human surgical specimens from patients of Dr. Roper.  After several weeks of development, the rats are sacrificed for histological and physiological studies.  I am primarily involved with the actual surgical implantation of the AHNPs and histological examination of these samples by counting and identifying surviving transplanted neurons, interneurons, and synaptic terminals. 

 

 

 

Differentiation of AHNPs into neuronal cell types. (A) Proliferating cells (30 PDs) assume a compacted morphology immediately after removal of mitogens and addition of dibutyl cAMP, IBMX and NGF. (B) Three days after induction of differentiation, intermediate cells displaying a developmentally intermediate phenotype are appreciated. (C) Five days after induction of differentiation, maturing cells concurrently lose GFAP and continue to strongly express B-III-tubulin. (D) Seven days after induction of differentiation, newly generated neurons in vitro frequently co-express immature neuron markers, and assume typical bipolar morphologies. (E) Current and voltage clamp analysis of 7-day-old neurons. New neurons exhibit prominent Na+ and K+ channels, and were able to fire elicited action potentials when polarized to –60 mV. (F) B-III-tubulin neurons generated in the presence of thymidine analog universally incorporate BrdU. Cells generated in this manner display additional type-specific neuronal markers, including PSA-NCAM (G) and neurofilament M (NF-M, H). Scale bars: 75 um in A; 25 um in B,H; 100 um in C,G. Cells counterstained with DAPI. From: Walton, et al., (2006).