2008 SURI Intern

Year:      Sophomore
Major:    Molecular, Cellular & Developmental
                Biology
School:  Yale University,
                New Haven, CT

Mentor:  Jason Huber, PhD., and
                Charles Rosen, M.D., Ph.D.
Dept:      Basic Pharmaceutical Sciences;
                Neurosurgery

---

Research Project

In the primary project, my main responsibility will be to perform functional analysis tests on old stroke rats receiving tissue plasminogen activator (TPA) as well as on old stroke rats receiving TPA plus Byrostatin (an anti-cancer agent). TPA is currently the drug of choice for the treatment of strokes and is administered within three hours of a stroke. Byrostatin is typically used as an anti-cancer agent but is hypothesized to generate new neuron growth as a side effect. It is thought that this side effect could ultimately be useful in stroke rats, assisting with the replacement of necrotic, non-functioning neurons with new, healthy neurons.

To evaluate this hypothesis, old rats will be functionally analyzed one day prior to an induced stroke and then be reevaluated at 24 hours after the induced stroke and subsequently one week, two weeks, and three weeks after the induced stroke. If the Byrostatin is effective, then the rats receiving the TPA injection as well as the Byrostatin should demonstrate greater improvement in the long-term functional analysis tests than the old stroke rates solely treated with TPA.

In the secondary project, I will assist with RNA isolations from various tissues in diabetic and healthy rats. One group of diabetic and healthy rats will receive no treatment for diabetes and the other group will receive treatment with Seasamol. Seasamol is a drug believed to have antioxidant capabilities that may help to lessen some of the adverse effects of diabetes on rat tissues.

The RNA isolated from these tissues will be converted to cDNA for storage purposes, due to increased stability in the cDNA form. The cDNA will then be used in PCR. After PCR, various probes will be used to test for the expression of specific genes in each tissue—most importantly genes for certain tight junction proteins in brain tissue, including claudins and occludins. Decreased expression of these tight-junction proteins indicates increased permeability of the blood-brain barrier. It has been found that diabetic rats demonstrate increased blood-brain barrier permeability, which provides serious implications for the increased susceptibility of the brain to toxicity.

Click here to review the summary report of this project.