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(Neurophysiology)

Professor and Vice Chair
Ph.D.: Medical College of Pennsylvania

My major research interest is to understand how the brain is affected by lack of oxygen (i.e., hypoxia) and what strategies the brain has for coping with hypoxia. This is important for understanding how a stroke (i.e., ischemia) damages the brain and how ischemic brain injury can be prevented. Although it is well known that several minutes of severe hypoxia can damage the brain irreversibly, it is less well known that there is a spectrum of vulnerability to hypoxia-ischemia among different brain regions and even among neurons within a given region. For example, the hippocampus, a brain structure important for memory and learning, has subregions that display widely varying vulnerabilities to hypoxic-ischemic damage. The focus of my research program is to determine what factors make some hippocampal neurons highly susceptible to injury and other hippocampal neurons resistant to injury. Our investigations are conducted in the hippocampal slice preparation, which is an in vitro prepartion of brain tissue. When neurons are exposed to hypoxia-ischemia, the first effect is a blockade of synaptic transmission and subsequently blockade of action potential activity. Blockade of action potentials is secondary to a profound increase in membrane permeality to all major ions. Ion concentration gradients run down and the neurons depolarize profoundly, if not completely. The influx of sodium and chloride ions also brings water into the cells by osmosis and cells swell. The depolarization is monitored by recording tissue electrical activity with microelectrodes and swelling is measured optically because water influx changes the optical properties of the tissue. The spatial extent of swelling is monitored by imaging light transmittance through the tissue slice with a digital vidio camera. Our recent experiments have shown that the CA1 region of the hippocampaus is highly vulnerable to hypoxic injury whereas the CA3 region is highly resistant, just like they are in the intact animal. Interestingly, pre-treatment of the slices with metabolic inhibitors or stressing the tissue in a variety of ways converts the CA3 region from a resistant area to a more vulnerable one. This gives us an important lever to investigate mechanisms of resistance and vulnerability. We are now beginning to investigate intracellular signaling mechanisms, and activation of immediate early genes, that might be responsible for the resistance/vulnerability.

Recent Publications:

A PubMed listing of research publications for Norman R. Kreisman, Ph.D.

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