Duke Institute for Brain Sciences

The Multidisciplinary Neuroprotection Laboratories 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 unique methods of oxygen delivery to tissue, interactions between anesthetics and injured brain, oxidative stress, and catalytic dismutation of 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. Recent focus has been on post-translational protein modification by sumoylation events and implications for protein fate during reperfusion. Primary neuronal/glial cultures, organotypic hippocampal slices and immortalized transfected human cell lines are used investigate mechanistic interactions between pharmacologic agents and metabolic stresses.

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

B.A., University of Wisconsin-Madison, 1976

Takata K, Sheng H, Borel C, Warner DS, Lombard FW (2008). Cerebral hypoperfusion, neuronal loss and persistent cognitive impairment: Novel perspectives on a rodent model of subarachnoid hemorrhage. Exp Neurol 213: 336-344.

Yang W, Sheng H, Homi M, Warner DS, Paschen W (2008). Cerebral ischemia/stroke and small ubiquitin-like modifier (SUMO) conjugation – A new target for therapeutic intervention? J Neurochem 106: 989-999.

Yang W, Sheng H, Warner DS, Paschen W. (2008). Transient focal cerebral ischemia induces a dramatic activation of small ubiquitin-like modifier conjugation. J Cereb Blood Flow Metab 28(5):892-896.