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

Selected Grants

Multidisciplinary Neonatal Training Grant awarded by National Institutes of Health (Mentor). 2010 to 2015

Fe porphyrin-based Redox Modulator in Experimental Stroke Outcome awarded by National Institutes of Health (Collaborator). 2013 to 2015

S-Nitrosylated Hemoglobin and Ischemic Brain Injury awarded by National Institutes of Health (Principal Investigator). 2009 to 2012

Ethyl Nitrite and Subarachnoid Hemorrhage awarded by National Institutes of Health (Co Investigator). 2008 to 2011

Shutdown of Translation and Ischemia/Stroke-Induced Cell Death awarded by National Institutes of Health (Collaborator). 2008 to 2010

Defining the Learning Curve in Research Trials awarded by National Institutes of Health (Co Investigator). 2004 to 2009

Biomedical and Biological Research Applications of a Storage-Ring Free-Electron Laser awarded by Air Force Office of Scientific Research (Co Investigator). 2000 to 2008

Anesthetics, GABA and the Injured Brain awarded by National Institutes of Health (Principal Investigator). 2003 to 2008

Trangenic Mouse Model of Alzheimer's Disease awarded by National Institutes of Health (Mentor). 2003 to 2006

Role of Extracellular Oxygen Radicals in Ischemic Brain awarded by National Institutes of Health (Principal Investigator). 2000 to 2005

Pages

Jiang, Meng, et al. “XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.Stroke, vol. 48, no. 6, June 2017, pp. 1646–54. Pubmed, doi:10.1161/STROKEAHA.117.016579. Full Text

Warner, David S., and Huaxin Sheng. “Anesthetic Neuroprotection? It's Complicated.Anesthesiology, vol. 126, no. 4, Apr. 2017, pp. 579–81. Pubmed, doi:10.1097/ALN.0000000000001535. Full Text

Yu, Zhui, et al. “Activation of the ATF6 branch of the unfolded protein response in neurons improves stroke outcome.J Cereb Blood Flow Metab, vol. 37, no. 3, Mar. 2017, pp. 1069–79. Pubmed, doi:10.1177/0271678X16650218. Full Text

Zhang, Lin, et al. “Neuron-specific SUMO knockdown suppresses global gene expression response and worsens functional outcome after transient forebrain ischemia in mice.Neuroscience, vol. 343, Feb. 2017, pp. 190–212. Pubmed, doi:10.1016/j.neuroscience.2016.11.036. Full Text

Berger, Miles, et al. “The Effect of Propofol vs. Isoflurane Anesthesia on Postoperative Changes in Cerebrospinal Fluid Cytokine Levels: Results from a Randomized Trial.Front Immunol, vol. 8, 2017, p. 1528. Pubmed, doi:10.3389/fimmu.2017.01528. Full Text

Taninishi, Hideki, et al. “Video training and certification program improves reliability of postischemic neurologic deficit measurement in the rat.J Cereb Blood Flow Metab, vol. 36, no. 12, Dec. 2016, pp. 2203–10. Pubmed, doi:10.1177/0271678X15616980. Full Text

Sasaki, Toshihiro, et al. “Long-Term Cognitive Deficits After Subarachnoid Hemorrhage in Rats.Neurocrit Care, vol. 25, no. 2, Oct. 2016, pp. 293–305. Pubmed, doi:10.1007/s12028-016-0250-1. Full Text

Hoffmann, Ulrike, et al. “Anesthesia in Experimental Stroke Research.Transl Stroke Res, vol. 7, no. 5, Oct. 2016, pp. 358–67. Pubmed, doi:10.1007/s12975-016-0491-5. Full Text

Warner, David S., and William L. Lanier. “Michael M. Todd, M.D., Recipient of the 2016 Excellence in Research Award.Anesthesiology, Aug. 2016. Pubmed, doi:10.1097/ALN.0000000000001291. Full Text

Lee, Han Kyu, et al. “Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume.J Clin Invest, vol. 126, no. 8, Aug. 2016, pp. 2827–38. Pubmed, doi:10.1172/JCI84491. Full Text

Pages

McGirt, M. J., et al. “Statins improve neurological outcome, attenuate hippocampal neuronal degeneration, and decrease interleukin-6 expression after experimental traumatic brain injury.” Neurosurgery, vol. 53, no. 2, LIPPINCOTT WILLIAMS & WILKINS, 2003, pp. 481–481.

Leinenweber, S. B., et al. “Expression of extracellular superoxide dismutase is increased after traumatic brain injury.” Critical Care Medicine, vol. 31, no. 2, 2003, pp. A13–A13.

Sheng, H. X., et al. “Mn(III) meso tetrakis(N,N '-diethylimidazolium-2-yl)porphyrin (AEOL-10150) offers protection in mouse model of spinal cord injury.” Free Radical Biology and Medicine, vol. 35, PERGAMON-ELSEVIER SCIENCE LTD, 2003, pp. S154–S154.

Warner, D. S. “Anesthesia for craniotomy.” Anesthesia and Analgesia, vol. 94, no. 3, LIPPINCOTT WILLIAMS & WILKINS, 2002, pp. 115–21.

Sheng, H. X., et al. “Mn(III) meso-tetrakis(ortho N-ethyl-pyridyl)porphyrin, MnTE-2-PyP (AEOL-10113) offers protection in mouse spinal cord injury model.” Free Radical Biology and Medicine, vol. 33, PERGAMON-ELSEVIER SCIENCE LTD, 2002, pp. S436–S436.

Warner, D. S. “Mild hypothermic brain protection.” Neuroanesthesia, edited by J. O. Johnson et al., vol. 32, KLUWER ACADEMIC PUBL, 1997, pp. 331–43.

Warner, D. S. “Opioids and the neurosurgical patient.” Neuroanesthesia, edited by J. O. Johnson et al., vol. 32, KLUWER ACADEMIC PUBL, 1997, pp. 237–43.

Warner, D. S. “Effects of anesthetic agents on ischemic brain.” Neuroanesthesia, edited by J. O. Johnson et al., vol. 32, KLUWER ACADEMIC PUBL, 1997, pp. 165–77.

Pages