David S. Warner, MD

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• Anesthesiology

Department / Division:
Anesthesiology / Anesthesiology

Address:
DUMC 3094
Durham, NC 27710

Office Telephone:
(919) 684-6633

Fax Telephone:
(919) 684-6692

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

• Neurosurgery, University of Iowa, 1980-1982
• Anesthesiology, University of Iowa, 1983-1984

• Laboratory for Experimental Brain Research, University of Lund, Sweden, 1984-1985

Clinical Interests:
Neuroanesthesiology, general anesthesiology

Research Interests:
Humans may sustain a variety of forms of acute central nervous system injury including ischemia, trauma, vasospasm, and perinatal hypoxemia. The Multidisciplinary Neuroprotection Laboraotries are 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 roles of excitatory/inhibitory neurotransmitters and 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, allosteric modifiers of hemoglobin affinity for oxygen, recombinant apolipoprotein E and its peptide fragments, SNO-hemoglobin, and anesthetics on histologic and behavioral recovery from ischemic/traumatic insults. Advanced 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, organtypic hippocampal slices and immortalized transfected human cell lines are used investigate mechanistic interactions between pharmacologic agents and metabolic stresses.

Representative Publications:
Elsersy H, Sheng H, Lynch JR, Moldovan M, Pearlstein RD, Warner DS. Effects of isoflurane versus fentanyl-nitrous oxide anesthesia on long-term outcome from severe forebrain ischemia in the rat. Anesthesiology. 2004 May;100(5):1160-6. (2004) Abstract

Parra A, McGirt MJ, Sheng H, Laskowitz DT, Pearlstein RD, Warner DS. Mouse model of subarachnoid hemorrhage associated cerebral vasospasm: methodological analysis. Neurol Res. 2002 Jul;24(5):510-6. (2002) Abstract

Mackensen GB, Patel M, Sheng H, Calvi CL, Batinic-Haberle I, Day BJ, Liang LP, Fridovich I, Crapo JD, Pearlstein RD, Warner DS. Neuroprotection from delayed postischemic administration of a metalloporphyrin catalytic antioxidant. J Neurosci. 2001 Jul 1;21(13):4582-92. (2001) Abstract

Fabling JM, Gan TJ, El-Moalem HE, Warner DS, Borel CO. A randomized, double-blind comparison of ondansetron versus placebo for prevention of nausea and vomiting after infratentorial craniotomy. J Neurosurg Anesthesiol. 2002 Apr;14(2):102-7. (2002) Abstract

McGirt MJ, Lynch JR, Blessing R, Warner DS, Friedman AH, Laskowitz DT. Serum von Willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery. 2002 Nov;51(5):1128-35. (2002) Abstract

Sheng H, Enghild JJ, Bowler R, Patel M, Batinić-Haberle I, Calvi CL, Day BJ, Pearlstein RD, Crapo JD, Warner DS. Effects of metalloporphyrin catalytic antioxidants in experimental brain ischemia. Free Radic Biol Med. 2002 Oct 1;33(7):947-61. (2002) Abstract

Aono M, Lee Y, Grant ER, Zivin RA, Pearlstein RD, Warner DS, Bennett ER, Laskowitz DT. Apolipoprotein E Protects against NMDA Excitotoxicity. Neurobiol Dis. 2002 Oct;11(1):214-20. (2002) Abstract

McGirt MJ, Lynch JR, Parra A, Sheng H, Pearlstein RD, Laskowitz DT, Pelligrino DA, Warner DS. Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage. Stroke. 2002 Dec;33(12):2950-6. (2002) Abstract

Sheng H, Wang H, Homi HM, Spasojevic I, Batinic-Haberle I, Pearlstein RD, Warner DS. A no-laminectomy spinal cord compression injury model in mice. J Neurotrauma. 2004 May;21(5):595-603. (2004) Abstract

Borel CO, McKee A, Parra A, Haglund MM, Solan A, Prabhakar V, Sheng H, Warner DS, Niklason L. Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage. Stroke. 2003 Feb;34(2):427-33. (2003) Abstract

Lynch JR, Tang W, Wang H, Vitek MP, Bennett ER, Sullivan PM, Warner DS, Laskowitz DT. ApoE genotype and an apoE-mimetic peptide modify the systemic and CNS inflammatory response. J Biol Chem. 2003 Sep 24. (2003) Abstract

Aono M, Bennett ER, Kim KS, Lynch JR, Myers J, Pearlstein RD, Warner DS, Laskowitz DT. Protective effect of apolipoprotein E-mimetic peptides on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cell cultures. Neuroscience. 2003;116(2):437-45. (2003) Abstract

Lynch JR, Wang H, McGirt MJ, Floyd J, Friedman AH, Coon AL, Blessing R, Alexander MJ, Graffagnino C, Warner DS, Laskowitz DT. Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial. Stroke. 2005 Sep;36(9):2024-6. (2005) Abstract

McKee JA, Brewer RP, Macy GE, Phillips-Bute B, Campbell KA, Borel CO, Reynolds JD, Warner DS. Analysis of the brain bioavailability of peripherally administered magnesium sulfate: A study in humans with acute brain injury undergoing prolonged induced hypermagnesemia. Crit Care Med. 2005 Mar;33(3):661-6. (2005) Abstract

McAdoo JD, Warner DS, Goldberg RN, Vitek MP, Pearlstein R, Laskowitz DT. Intrathecal administration of a novel apoE-derived therapeutic peptide improves outcome following perinatal hypoxic-ischemic injury. Neurosci Lett. 2005 Jun 24;381(3):305-8. (2005) Abstract

Wang JK, Portbury S, Thomas MB, Barney S, Ricca DJ, Morris DL, Warner DS, Lo DC. Cardiac glycosides provide neuroprotection against ischemic stroke: discovery by a brain slice-based compound screening platform. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10461-6. (2006) Abstract

Freiberger JJ, Suliman HB, Sheng H, McAdoo J, Piantadosi CA, Warner DS. A comparison of hyperbaric oxygen versus hypoxic cerebral preconditioning in neonatal rats. Brain Res. 2006 Feb 23;1075(1):213-22. (2006) Abstract

Elsersy H, Mixco J, Sheng H, Pearlstein RD, Warner DS. Selective gamma-aminobutyric acid type A receptor antagonism reverses isoflurane ischemic neuroprotection. Anesthesiology. 2006 Jul;105(1):81-90. (2006) Abstract

Wang H, Lynch JR, Song P, Yang HJ, Yates RB, Mace B, Warner DS, Guyton JR, Laskowitz DT. Simvastatin and atorvastatin improve behavioral outcome, reduce hippocampal degeneration, and improve cerebral blood flow after experimental traumatic brain injury. Exp Neurol. 2007 Jul;206(1):59-69. (2007) Abstract

Sakai H, Sheng H, Yates RB, Ishida K, Pearlstein RD, Warner DS. Isoflurane provides long-term protection against focal cerebral ischemia in the rat. Anesthesiology. 2007 Jan;106(1):92-9; discussion 8-10. (2007) Abstract

Wang H, Durham L, Dawson H, Song P, Warner DS, Sullivan PM, Vitek MP, Laskowitz DT. An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interaction. Neuroscience. 2007 Feb 23;144(4):1324-33. (2007) Abstract

Fukuda S, Warner DS. Cerebral protection. Br J Anaesth. 2007 Jul;99(1):10-7. (2007) Abstract

Yang W, Sheng H, Warner DS, Paschen W. Transient global cerebral ischemia induces a massive increase in protein sumoylation. J Cereb Blood Flow Metab. 2007 Jun 13. (2007) Abstract