Cerebral ischemia is a frequent consequence during cardiac and neurological surgery. In surgical procedures with a high risk of ischemia, it is important to choose an anesthetic that offers protection. Our studies examine how anesthetics reduce hypoxic and ischemic damage and aim to increase the understanding of damaging mechanisms thus improving the treatment and prevention of neuronal damage. We study anesthetics and other agents that are thought to improve recovery as well as blockers of specific pathways thought to induce or ameliorate neuronal damage due to hypoxia or ischemia. One focus of our studies is to examine the effects of anesthetics and other agents in the period before hypoxia and ischemia and determine how the cellular and molecular changes due to these anesthetics enhance recovery after the insult. We compare anesthetics present only before the insult with the effect of the anesthetic agents during the insult in order to differentiate the direct effect of anesthesia from preconditioning effects. We are examining the cellular and molecular mechanism by which anesthetics and other agents protect using an in vitro brain slice model and in vivo global and focal cerebral ischemic models. We use pharmacologic methods, western blots, immunohistochemistry, intracellular and extracellular electrophysiological techniques, fluorescent dyes and behavioral studies to examine the mechanisms leading to brain damage after hypoxia and ischemia.
Double-labeling of cytochrome C (A); active caspase 3 (C); and TUNEL (E) with NeuN (B; D and F respectively). After 90 min of focal cerebral ischemia, there were significantly less Cytochrome C and Caspase 3 cells at 4 hours and TUNEL cells at 24 hours in the lidocaine treated animals. Figures from Lei, B., et. al. 2004 (reference below).
Effect of sevoflurane on the membrane potential and cytosolic calcium levels measured in rat hippocampal slice CA 1 pyramidal cells subjected to 10 min of hypoxia. Figures from Wang J., et. al. 2006 (reference below)
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Amorim, P., Cottrell, J. E., and Kass, I. S. (1999). Effect of small changes in temperature on CA1 pyramidal cells from rat hippocampal slices during hypoxia: implications about the mechanism of hypothermic protection against neuronal damage. Brain Res. 844, 143-149.
Wang, T., Raley-Susman, K. M., Wang, J., Chambers, G., Cottrell, J. E., and Kass, I. S. (1999). Thiopental attenuates hypoxic changes of electrophysiology, biochemistry and morphology in rat hippocampal slice CA1 pyramidal cells. Stroke 30, 2400-2407.
Wang, J., Chambers, G., Cottrell, J. E., and Kass, I. S. (2000). Differential fall in ATP accounts for effects of temperature on hypoxic damage in rat hippocampal slices. J. Neurophysiol. 83, 3462-3472.
Raley-Susman, K. M., Kass, I. S., Cottrell, J. E., Newman, R., Chambers, G., and Wang, J. (2001). Sodium influx blockade and hypoxic damage to CA1 pyramidal neurons in rat hippocampal slices. J. Neurophysiol. 86, 2715-2726.
Lei, B., Popp, S., Capuano-Waters, C., Cottrell, J. E., and Kass, I. S. (2004). Lidocaine attenuates apoptosis in the ischemic penumbra and reduces infarct size after transient focal cerebral ischemia in rats. Neuroscience 125, 691-701.
Wang, T., Wang, J., Cottrell, J. E., and Kass, I. S. (2004). Small physiologic changes in calcium and magnesium alter excitability and burst firing of CA1 pyramidal cells in rat hippocampal slices. J. Neurosurgical Anesthesiol. 16, 201-209.
Libien, J., Sacktor, T. C., and Kass, I. S. (2005). Magnesium blocks the loss of protein kinase C, leads to a transient translocation of PKC and PKC, and improves recovery after anoxia in rat hippocampal slices. Mol. Brain Res. 136, 104-111.
Wang, J., Meng, F., Cottrell, J. E., and Kass, I. S. (2006). The differential effects of volatile anesthetics on electrophysiological and biochemical changes during and recovery after hypoxia in rat hippocampal slice CA1 pyramidal cells. Neuroscience 140, 957-967.
Wang, J., Lei, B., Popp, S., Meng, F., Cottrell, J. E., and Kass, I. S. (2007). Sevoflurane immediate preconditioning alters hypoxic membrane potential changes in rat hippocampal slices and improves recovery of CA1 pyramidal cells after hypoxia and global cerebral ischemia. Neuroscience 145, 1097-1107.
Jun Wang, M.D., Senior Research Scientist, Research Assistant Professor
Susanna Popp, Ph.D., Postdoctoral Fellow
Fanli Meng, M.S., Graduate Student
Baiping Lei, M.D., Ph.D., Anesthesiology Resident Physician
Editorial Board: Journal of Neurosurgical Anesthesiology, Raven Press.
Member: Sub-Committee on Current Research, New York State Society of Anesthesiologists.