Physicians

Departments / Divisions

• Anesthesiology / Anesthesiology-Neuro Division
• Neurobiology
• Surgery

Address
DUMC 3094
Durham, NC 27710

Office Telephone
919-684-6633

Fax Telephone
919-684-6692

Training

• MD, University of Wisconsin School of Medicine and Public Health, 1980

Residency

• Neurosurgery, University of Iowa Hospitals and Clinics, 1980-1982
• Anesthesiology, University of Iowa Hospitals and Clinics, 1982-1984

Fellowship

• Laboratory for Experimental Brain Research, Lund University (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 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.

Industry Relationships and Collaborations (What's this?)

This faculty member (or a member of their immediate family) has a working relationship (i.e. consulting, research, and/or educational services) with the companies listed below. These relations have been reported to the health system leadership and, when appropriate, management plans are in place to address potential conflicts.

• BioMimetix Pharmaceutical, Inc.

Representative Publications
Yates, RB; Sheng, H; Sakai, H; Kleven, DT; DeSimone, NA; Stafford-Smith, M; Warner, DS. Lack of evidence for a remote effect of renal ischemia/reperfusion acute kidney injury on outcome from temporary focal cerebral ischemia in the rat. Journal of Cardiothoracic and Vascular Anesthesia. 2013;27:71-78. (2013) Abstract

Indraswari, F; Wang, H; Lei, B; James, ML; Kernagis, D; Warner, DS; Dawson, HN; Laskowitz, DT. Statins improve outcome in murine models of intracranial hemorrhage and traumatic brain injury: a translational approach. Journal of Neurotrauma. 2012;29:1388-1400. (2012) Abstract

Rajic, Z; Tovmasyan, A; Spasojevic, I; Sheng, H; Lu, M; Li, AM; Gralla, EB; Warner, DS; Benov, L; Batinic-Haberle, I. A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity. Free Radical Biology and Medicine. 2012;52:1828-1834. (2012) Abstract

Topjian, AA; Berg, RA; Bierens, JJ; Branche, CM; Clark, RS; Friberg, H; Hoedemaekers, CW; Holzer, M; Katz, LM; Knape, JT; Kochanek, PM; Nadkarni, V; van der Hoeven, JG; Warner, DS. Brain resuscitation in the drowning victim. Neurocritical Care. 2012;17:441-467. (2012) Abstract

Tovmasyan, A; Sheng, H; Weitner, T; Arulpragasam, A; Lu, M; Warner, DS; Vujaskovic, Z; Spasojevic, I; Batinic Haberle, I. Design, Mechanism of Action, Bioavailability and Therapeutic Effects of Mn Porphyrin-Based Redox Modulators. Medical Principles and Practice. 2012; (2012) Abstract

Guinn, NR; McDonagh, DL; Borel, CO; Wright, DR; Zomorodi, AR; Powers, CJ; Warner, DS; Lam, AM; Britz, GW. Adenosine-induced transient asystole for intracranial aneurysm surgery: a retrospective review. Journal of Neurosurgical Anesthesiology. 2011;23:35-40. (2011) Abstract

Sheng, H; Reynolds, JD; Auten, RL; Demchenko, IT; Piantadosi, CA; Stamler, JS; Warner, DS. Pharmacologically augmented S-nitrosylated hemoglobin improves recovery from murine subarachnoid hemorrhage. Stroke. 2011;42:471-476. (2011) Abstract

Sheng, H; Spasojevic, I; Tse, HM; Jung, JY; Hong, J; Zhang, Z; Piganelli, JD; Batinic-Haberle, I; Warner, DS. Neuroprotective efficacy from a lipophilic redox-modulating Mn(III) N-Hexylpyridylporphyrin, MnTnHex-2-PyP: rodent models of ischemic stroke and subarachnoid hemorrhage. Journal of Pharmacology and Experimental Therapeutics. 2011;338:906-916. (2011) Abstract

Tovmasyan, AG; Rajic, Z; Spasojevic, I; Reboucas, JS; Chen, X; Salvemini, D; Sheng, H; Warner, DS; Benov, L; Batinic-Haberle, I. Methoxy-derivatization of alkyl chains increases the in vivo efficacy of cationic Mn porphyrins. Synthesis, characterization, SOD-like activity, and SOD-deficient E. coli study of meta Mn(III) N-methoxyalkylpyridylporphyrins. Dalton Transactions: an international journal of inorganic chemistry. 2011;40:4111-4121. (2011) Abstract

Pearlstein, RD; Higuchi, Y; Moldovan, M; Johnson, K; Fukuda, S; Gridley, DS; Crapo, JD; Warner, DS; Slater, JM. Metalloporphyrin antioxidants ameliorate normal tissue radiation damage in rat brain. International Journal of Radiation Biology. 2010;86:145-163. (2010) Abstract

Wang, Z; Yang, W; Britz, GW; Lombard, FW; Warner, DS; Sheng, H. Development of a simplified spinal cord ischemia model in mice. Journal of Neuroscience Methods. 2010;189:246-251. (2010) Abstract

Mackensen, GB; McDonagh, DL; Warner, DS. Perioperative hypothermia: use and therapeutic implications. Journal of Neurotrauma. 2009;26:342-358. (2009) Abstract

Sheng, H; Yang, W; Fukuda, S; Tse, HM; Paschen, W; Johnson, K; Batinic-Haberle, I; Crapo, JD; Pearlstein, RD; Piganelli, J; Warner, DS. Long-term neuroprotection from a potent redox-modulating metalloporphyrin in the rat. Free Radical Biology and Medicine. 2009;47:917-923. (2009) Abstract

Takata, K; Sheng, H; Borel, CO; Laskowitz, DT; Warner, DS; Lombard, FW. Simvastatin treatment duration and cognitive preservation in experimental subarachnoid hemorrhage. Journal of Neurosurgical Anesthesiology. 2009;21:326-333. (2009) Abstract