David Samuel Warner

David Samuel Warner

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 at Madison 1980

Selected Grants

Duke CTSA (TL1) awarded by National Institutes of Health (Mentor). 2018 to 2023

Duke CTSA (KL2) awarded by National Institutes of Health (Mentor). 2018 to 2023

The Unfolded Protein Response and Neuroprotection in Stroke awarded by National Institutes of Health (Significant Contributor). 2016 to 2021

Integrated Training in Anesthesiology Research awarded by National Institutes of Health (Principal Investigator). 1996 to 2021

Translating Endogenous Vascular Protective Cascades into Therapy for Aneurysmal Subarachnoid Hemorrhage awarded by Washington University in St. Louis (Principal Investigator). 2015 to 2020

Effect of Aging on Brain Ischemia/Stroke Outcome; Pathways, Mechanisms, and Rescue awarded by National Institutes of Health (Significant Contributor). 2016 to 2020

Translating Endogenous Vascular Protective Cascades into Therapy for Aneurysmal Subarachnoid Hemorrhage awarded by Washington University in St. Louis (Principal Investigator). 2015 to 2019

Xenon As A Therapeutic in Experimental Intracerebral Hemorrhage awarded by National Institutes of Health (Principal Investigator). 2015 to 2018

The trajectory and significance of perioperative changes in AD biomarkers awarded by International Anesthesia Research Society (Significant Contributor). 2014 to 2018

STIM1-dependent calcium signaling in neuronal responses to hypoxia and ischemia awarded by National Institutes of Health (Collaborator). 2015 to 2017

Pages

Ma, Shuang, et al. “Argon Inhalation for 24 Hours After Onset of Permanent Focal Cerebral Ischemia in Rats Provides Neuroprotection and Improves Neurologic Outcome..” Crit Care Med, vol. 47, no. 8, Aug. 2019, pp. e693–99. Pubmed, doi:10.1097/CCM.0000000000003809. Full Text

Terrando, Niccolò, and David S. Warner. “Xenon for traumatic brain injury: a noble step forward and a wet blanket..” Br J Anaesth, vol. 123, no. 1, July 2019, pp. 9–11. Pubmed, doi:10.1016/j.bja.2019.04.004. Full Text

Klinger, Rebecca Y., et al. “Intravenous Lidocaine Does Not Improve Neurologic Outcomes after Cardiac Surgery: A Randomized Controlled Trial..” Anesthesiology, vol. 130, no. 6, June 2019, pp. 958–70. Pubmed, doi:10.1097/ALN.0000000000002668. Full Text

Xie, Yongqiu, et al. “Sex Differences in Gene and Protein Expression After Intracerebral Hemorrhage in Mice..” Transl Stroke Res, vol. 10, no. 2, Apr. 2019, pp. 231–39. Pubmed, doi:10.1007/s12975-018-0633-z. Full Text

Klinger, Rebecca Y., et al. “18F-florbetapir Positron Emission Tomography-determined Cerebral β-Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery..” Anesthesiology, vol. 128, no. 4, Apr. 2018, pp. 728–44. Pubmed, doi:10.1097/ALN.0000000000002103. Full Text

Agarwal, Piyush K. “Editorial Comment..” J Urol, vol. 199, no. 2, Feb. 2018, pp. 414–15. Pubmed, doi:10.1016/j.juro.2017.08.132. Full Text

Liu, Huaqin, et al. “Novel Modification of Potassium Chloride Induced Cardiac Arrest Model for Aged Mice..” Aging Dis, vol. 9, no. 1, Feb. 2018, pp. 31–39. Pubmed, doi:10.14336/AD.2017.0221. Full Text

Idris, Ahamed H., et al. “2015 revised Utstein-style recommended guidelines for uniform reporting of data from drowning-related resuscitation: An ILCOR advisory statement..” Resuscitation, vol. 118, Sept. 2017, pp. 147–58. Pubmed, doi:10.1016/j.resuscitation.2017.05.028. Full Text

Idris, Ahamed H., et al. “2015 Revised Utstein-Style Recommended Guidelines for Uniform Reporting of Data From Drowning-Related Resuscitation: An ILCOR Advisory Statement..” Circ Cardiovasc Qual Outcomes, vol. 10, no. 7, July 2017. Pubmed, doi:10.1161/HCQ.0000000000000024. Full Text

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

Pages

Ma, Shuang, et al. “24 HOUR POST-TREATMENT WITH THE NOBLE GAS ARGON PROVIDES ROBUST NEUROPROTECTION AND IMPROVEMENT IN NEUROLOGIC OUTCOME AFTER FOCAL CEREBRAL ISCHEMIA IN RATS.” Anesthesia and Analgesia, vol. 126, no. 4, LIPPINCOTT WILLIAMS & WILKINS, 2018, pp. 312–312.

Sheng, H., et al. “Xenon as a therapy in experimental intracerebral hemorrhage.” Journal of Cerebral Blood Flow and Metabolism, vol. 37, SAGE PUBLICATIONS INC, 2017, pp. 451–451.

Lei, Beilei, et al. “Progesterone Improves Neurobehavioral Outcome in Models of Intracerebral Hemorrhage..” Neuroendocrinology, vol. 103, no. 6, 2016, pp. 665–77. Pubmed, doi:10.1159/000442204. Full Text

Rajic, Zrinka, et al. “A Breakthrough in the Development of SOD Mimics/Cellular Redox Modulators: a Superior Mn porphyrin, MnTnBuOE-2-PyP5+ With Finely Tuned Properties.” Free Radical Biology and Medicine, vol. 51, Elsevier BV, 2011, pp. S95–S95. Crossref, doi:10.1016/j.freeradbiomed.2011.10.462. Full Text

Tovmasyan, Artak, et al. “Structural Modification Diminishes Toxicity of Lipophilic Longer Mn(III) N-alkylpyridyl porphyrin-based Powerful SOD Mimics: Synthesis, Characterization and SOD-deficient E. coli and S. cerevisiae studies.” Free Radical Biology and Medicine, vol. 49, Elsevier BV, 2010, pp. S201–S201. Crossref, doi:10.1016/j.freeradbiomed.2010.10.583. Full Text

Kos, Ivan, et al. “Oral Availability of Mnte-2-Pyp(5+), a Potent Antioxidant and Cellular Redox Modulator.” Free Radical Biology and Medicine, vol. 45, ELSEVIER SCIENCE INC, 2008, pp. S86–87.

McAdoo, J. D., et al. “Apolipoprotein E-mimetic peptide reduces brain injury in a neonatal hypoxia-ischemia model.” Pediatric Research, vol. 55, no. 4, INT PEDIATRIC RESEARCH FOUNDATION, INC, 2004, pp. 408A-408A.

Lynch, J. R., et al. “An ApoE-based therapeutic improves outcome and reduces Alzheimer's disease pathology after head injury.” Annals of Neurology, vol. 56, WILEY-LISS, 2004, pp. S42–S42.

Warner, D. S., et al. “Ec-SOD overexpression reduces blood-spinal cord barrier permeability and inflammatory cell infiltration, but does not improve outcome from spinal cord compression injury in the mouse.” Free Radical Biology and Medicine, vol. 37, PERGAMON-ELSEVIER SCIENCE LTD, 2004, pp. S165–S165.

Pages

Mackensen, G. B., et al. “Cerebral embolization during cardiac surgery: impact of aortic atheroma burden..” Br J Anaesth, vol. 91, no. 5, Nov. 2003, pp. 656–61. Pubmed, doi:10.1093/bja/aeg234. Full Text

Swaminathan, Madhav, et al. “Serum creatinine patterns in coronary bypass surgery patients with and without postoperative cognitive dysfunction..” Anesth Analg, vol. 95, no. 1, July 2002, pp. 1–8. Pubmed, doi:10.1097/00000539-200207000-00001. Full Text

Grigore, Alina M., et al. “The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery..” Anesth Analg, vol. 94, no. 1, Jan. 2002, pp. 4–10. Pubmed, doi:10.1097/00000539-200201000-00002. Full Text