Dr. Kreisman’s early research was in the investigation of epilepsy, particularly cerebral blood flow and oxygen delivery in status epilepticus. His findings showed that deficiency of cerebral blood flow and oxygen delivery to the cortex was primarily due to compromises in systemic cardio-pulmonary function. His more recent research interest was in understanding endogenous mechanisms protecting against brain injury in response to hyoxia-ischemia. There are two lines of evidence for the existence of these mechanisms: 1) conditioning the brain with one or more mild episodes of hypoxia/ischemia protects the brain from subsequent hypoxic/ischemic insults. Protection lasts for hours to days. This is known as ischemic preconditioning or ischemic tolerance. The explanation for this acquired tolerance to hypoxia/ischemia is that conditioning stimuli activate endogenous protective mechanisms that remain in effect for an extended period. 2) Various regions of the brain display selective vulnerability/resistance to hypoxic/ischemic injury. A spectrum of vulnerabilities even exists within structures known to be very susceptible to injury, such as the hippocampus. Using hippocampal slices, we are testing the hypothesis that selective resistance to ischemic insults is related to the propensity of a particular region to undergo ischemic preconditioning. Optical and electrophysiological techniques are used to monitor cell swelling and depolarization, which are early signs of ischemic injury. Currently, we are investigating the role of the paracrine cytokine, erythropoietin as a mediator of preconditioning by exploring its downstream signaling pathways. Our hope is that these investigations will point toward future therapeutic regimens to ameliorate the devastating effects of strokes.