David Samuel Warner

David Samuel Warner

Distinguished Distinguished Professor of Anesthesiology, in the School of Medicine

External Address: 
303 Research Dr., 134 Sands Buildign, Durham, NC 27710
Internal Office Address: 
Box 3094 Med Ctr, Durham, NC 27710
Phone: 
919.684.6633

Overview

Humans may sustain a variety of forms of acute central nervous system injury including ischemia, trauma, vasospasm, and perinatal hypoxemia. The Multidisciplinary Neuroprotection Laboratories is dedicated to examining the pathophysiology of acute brain and spinal cord injury with particular reference to disease states managed in the perioperative or neurointensive care environments. Rodent recovery models of cerebral ischemia, traumatic brain injury, cardiopulmonary bypass, subarachnoid hemorrhage, spinal cord ischemia, and perinatal hypoxia have been established with requisite control of relevant physiologic variables. Experimental protocols examine the response of brain to these insults and seek to define appropriate therapeutic interventions. Our work examines the role reactive oxygen species in CNS injury with emphasis on how pharmacologic or genetic variants modulate these processes. Effects of altered synthesis of superoxide dismutase and apolipoprotein E are investigated in transgenic/knock out mice. Outcome studies allow definition of efficacy of pharmacologic agents including superoxide dismutase mimetics, PARP-1 inhibitors, hepatocyte growth factor mimetics, recombinant apolipoprotein E and its peptide fragments, SNO-hemoglobin, and anesthetics on histologic and behavioral recovery from ischemic/traumatic insults. Recent focus has been on SUMOylation responses of neural tissue to ischemic stress. Neurochemical, immunohistochemical, molecular biologic, genomic, and proteomic techniques are used to define the mechanistic basis of observations made in outcome studies. Primary neuronal/glial cultures, organotypic hippocampal slices and immortalized transfected human cell lines are used investigate mechanistic interactions between pharmacologic agents and metabolic stresses.

Education & Training

  • M.D., University of Wisconsin - Madison 1980

Bierens, Joost J. L. M., and David S. Warner. “Drowning resuscitation requires another state of mind.Resuscitation, vol. 84, no. 11, Nov. 2013, pp. 1467–69. Pubmed, doi:10.1016/j.resuscitation.2013.09.005. Full Text

Tovmasyan, Artak, et al. “Differential coordination demands in Fe versus Mn water-soluble cationic metalloporphyrins translate into remarkably different aqueous redox chemistry and biology.Inorg Chem, vol. 52, no. 10, May 2013, pp. 5677–91. Pubmed, doi:10.1021/ic3012519. Full Text

Benner, Eric J., et al. “Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4.Nature, vol. 497, no. 7449, May 2013, pp. 369–73. Pubmed, doi:10.1038/nature12069. Full Text

Weitner, Tin, et al. “Comprehensive pharmacokinetic studies and oral bioavailability of two Mn porphyrin-based SOD mimics, MnTE-2-PyP5+ and MnTnHex-2-PyP5+.Free Radic Biol Med, vol. 58, May 2013, pp. 73–80. Pubmed, doi:10.1016/j.freeradbiomed.2013.01.006. Full Text

Yates, Robert B., et al. “Lack of evidence for a remote effect of renal ischemia/reperfusion acute kidney injury on outcome from temporary focal cerebral ischemia in the rat.J Cardiothorac Vasc Anesth, vol. 27, no. 1, Feb. 2013, pp. 71–78. Pubmed, doi:10.1053/j.jvca.2012.06.012. Full Text

Tovmasyan, Artak, et al. “Design, mechanism of action, bioavailability and therapeutic effects of mn porphyrin-based redox modulators.Med Princ Pract, vol. 22, no. 2, 2013, pp. 103–30. Pubmed, doi:10.1159/000341715. Full Text

Benner, E. J., et al. “Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4.” Nature, vol. 497, no. 7449, 2013, pp. 369–73. Scival, doi:10.1038/nature12069. Full Text

Topjian, Alexis A., et al. “Brain resuscitation in the drowning victim.Neurocrit Care, vol. 17, no. 3, Dec. 2012, pp. 441–67. Pubmed, doi:10.1007/s12028-012-9747-4. Full Text

Sheng, Siyuan P., et al. “Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage.Anesthesiology, vol. 117, no. 6, Dec. 2012, pp. 1262–75. Pubmed, doi:10.1097/ALN.0b013e3182746b81. Full Text

Rajic, Zrinka, et al. “A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity.Free Radic Biol Med, vol. 52, no. 9, May 2012, pp. 1828–34. Pubmed, doi:10.1016/j.freeradbiomed.2012.02.006. Full Text

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