Stroke is a medical condition for which we do not have adequate medical treatments. The purpose of this project is to examine the factors that influence the success of using human stem cells to repair injury caused by a stroke (brain ischemia). Because so much remains to be known before stem cell therapies can be used in stroke patients, we propose studies which will create a model of stroke in the laboratory. The model involves slices of the rat hippocampus (a brain region important to learning and memory and very sensitive to stroke damage). A stroke-like insult can be produced in this explanted tissue and cell damage, repair and function of synapses in the tissue can be subsequently followed for long periods of time. The way in which we will examine the effect of human embryonic stem cells is by transplanting them ("seeding") onto the brain tissue in culture. The effects of the stem cells on repairing injury will then be followed over time. Some of the basic questions we will examine include how the specific location in the hippocampus affects the benefit of stem cell application, how the maturity of the stem cells controls neuroprotection, and if we can use new drugs being developed by a biotechnology company (NeuroNascent, Inc.) to improve the benefits of the stem cell therapy. These basic studies are needed to help guide future studies in animals, and eventually, in patients.
Stroke is a medical condition for which we have limited medical treatments. Repairing the brain following a stroke through the use of human embryonic stem cells offers the potential for improved stroke recovery. This work described in this proposal will address basic questions relating to the best ways to use stem cells to improve stroke recovery. Ultimately, the work will contribute to the health of the citizens of California by fostering the development of new treatments for stroke and related brain diseases.