Mount Union College, Alliance, OH BS, Biology 6/1972
Cornell University Graduate School of Medical Sciences, New York, NY PhD Pharmacology 5/1976
Cornell University Medical College, New York, NY Postdoctoral Fellowship 6/76-12/1977
Pharmacological Treatments for Acute Brain and Spinal Cord Injury
Traumatic brain injury (TBI) and spinal cord injury (SCI) are among the most serious consequences that human beings can suffer. In most cases of TBI and SCI, the neurological, economic and social consequences are devastating to the patient, his or her family and to society as a whole. Although high dose treatment with the glucocorticoid steroid methylprednisolone has been shown to have some beneficial effect in SCI patients, there are no clinically proven and approved pharmacological therapies for acute treatment of TBI patients aimed at mitigating the damaging neurological effects of their injuries. Nevertheless, hope for improved treatments for SCI and the possibility of an effective treatment for TBI is derived from the fact that although some of the neural injury in both instances is due to the primary mechanical events (i.e. shearing of nerve cells and blood vessels), the majority of post-traumatic degeneration is due to a pathochemical and pathophysiological cascade of secondary events occurring in the first minutes, hours and days which exacerbates the effects of the primary injury that can be interrupted by pharmacological approaches.
Dr. Hall's laboratory is focused upon the further understanding of the secondary injury process that follows mechanical trauma to the brain or spinal cord, and the discovery of novel pharmacological treatments that will inhibit post-traumatic neurodegeneration and/or enhance neurological recovery. His laboratory is presently interested in the roles of reactive oxygen-mediated oxidative and calpain-mediated cytoskeletal damage mechanisms and their pharmacological interruption.
Dr. Hall's ongoing research is funded by grants from the National Institute of Neurological Disorders and Stroke and the Kentucky Spinal Cord & Head Injury Research Trust.
R01 NS083405 (PI: Hall, E) 07/01/13-6/30/18
“Multi-mechanism inhibition of lipid peroxidation in TBI”
Goal: This project will examine the potentially greater benefits that might be obtained in the rat controlled cortical impact traumatic brain injury model when multiple neuroprotective compounds that target oxidative secondary injury mechanisms are administered together. Specifically, we will test a combination multi-mechanistic antioxidant treatment strategy combining two or three of the following mechanistically complimentary antioxidant compounds A.
R01 NS084857 (PI: Hall, E) 02/01/14-01/31/18
“Carbonyl scavenging for traumatic brain injury”
Goal: This project will examine the neuroprotective effects of phenelzine, a long-used anti-depressant compound that has recently been discovered to also be a scavenger of lipid peroxidation-derived carbonyl-containing aldehydes such as 4-hydroxynonenal and acrolein, in the rat controlled cortical impact traumatic brain injury model (CCI-TBI)
P30 NS051220 (PI: Hall, E) 05/01/05-11/30/15
“UK-SCoBIRC Center Core Grant”
Goal: This center grant funds the continued technical support and upgrading of five core facilities including an Administrative Core, an Animal Surgery & TBI/SCI Models Core, a Behavioral Testing Core, a Microscopy, Stereology & Image Analysis Core and a Molecular Mechanisms Core.
T32 NS077889 (MPI: Hall, E; Geddes, J) 07/01/12-06/30/17
“Neurobiology of CNS Injury & Repair Training Grant”
Goal: Supports graduate students who are interested in careers in neurotrauma research.
Trust Grant #14-4A (PI: Hall, E) 01/15/15-01/14/18
Kentucky Spinal Cord & Head Injury Research Trust Grant
“Oxidative damage and calcium-activated biomarkers after TBI and effects of cyclosporine A”
Goal: Phase II clinical study of cyclosporine A-response plasma biomarkers in severe TBI patients.
T32 DA022738 (PI: Hall, E) 09/26/06-06/30/12
“Therapeutic Strategies for Neurodegeneration Training Grant”
Goal: Supports graduate students, postdoctoral fellows and a clinical trainee who are interested in careers in translational neuroscience focused on spinal cord and brain injury, stroke and Parkinson’s disease.
Role: PI and Program Director
P01 NS058484 (PI: Geddes, J) 05/01/07-04/30/11
“Calpain as a Therapeutic Target for TBI”
Goal: This grant is directed at the discovery of improved calpain inhibitors for the acute treatment of traumatic brain injury. Project 2 was entitled, “Newer Small Molecule Calpain Inhibitors for TBI” Annual Direct Costs.”
Role: Project 2 Director
R21 NS077434 (PI: Hall, E) 09/16/11-08/31/13
“Inhibition of lipid peroxidation in SCI”
Goal: Investigate the neuroprotective effects of the lipid peroxidation inhibitor U-83836E alone and in combination with the carbonyl scavenger phenelzine in acute SCI in a rat contusion model.
Carrico, K.M., Vaishnav, RA and Hall, E.D. Temporal and spatial dynamics of peroxynitrite-induced oxidative damage after spinal cord contusion injury. J. Neurotrauma 26:1369-1378, 2009. PMCID 2850290
Vaishnav, R.A., Singh, I.N., Miller, D.M. and Hall, E.D. Lipid peroxidation-derived aldehydes directly and differentially impair spinal cord and brain mitochondrial function. J. Neurotrauma 27:1311-1320, 2010. PMCID 2942874
Mustafa, A.G., Singh, I.N., Carrico, K.M., Wang, J. and Hall, E.D. Mitochondrial protection after traumatic brain injury by scavenging lipid peroxyl radicals. J. Neurochem. 114:271-280, 2010. PMCID 3526891
Thompson, S.N., Carrico, K.M., Mustafa, A.G., Bains, M. and Hall, E.D.. A pharmacological analysis of the neuroprotective efficacy of the brain and cell permeable calpain inhibitor MDL-28170 in the the mouse controlled cortical impact traumatic brain injury model. J. Neurotrauma 27:2233-2244, 2010. PMCID 2996835
Mustafa, A.G., Wang, J.A., Carrico, K.M. and Hall, E.D. Pharmacological Inhibition of Lipid Peroxidation Attenuates Calpain-Mediated Cytoskeletal Degradation After Traumatic Brain Injury. J. Neurochem. 117:579-588, 2011. PMCID 3076544
Sullivan, P.G., Sebastian, A. and Hall, E.D. Therapeutic window analysis of the neuroprotective effects of cyclosporine A after traumatic brain injury. J. Neurotrauma 28:311-318, 2011. PMCID 3037811
Hall, E.D., Wang, J.A. and Miller, D.M. Relationship of nitric oxide synthase induction to peroxynitrite-mediated oxidative damage during the first week after experimental traumatic brain injury. Exp. Neurol. 238:176-182, 2012. PMCID 3498522
Miller, D.M., Singh, I.N. and Hall, E.D. Administration of Nrf2-ARE activators sulforaphane and carnosic acid attenuate 4-hydroxy-2-nonenal induced mitochondrial dysfunction ex vivo. Free Rad. Biol. Med. 57:1-9, 2013. PMCID 3594400
Singh, I.N., Gilmer, L.K., Miller, D.M., Cebak, J.E., Wang, J.A. and Hall, E.D. Phenelzine mitochondrial preservation and neuroprotection after traumatic brain injury related to scavenging of the lipid peroxidation-derived aldehyde 4-hydroxy-2-nonenal., J. Cereb. Blood Flow & Metab. 33: 593-599, 2013. PMCID 3618398
Bains, M., Cebak, J.E., Gilmer, L.K., Barnes, C., Thompson, S.N. and Hall, E.D. Pharmacological analysis of the cortical neuronal cytoskeletal protective efficacy of the calpain inhibitor SNJ-1945 in a mouse traumatic brain injury model. J. Neurochem. 125: 125-132, 2013.
Miller, D.M., Wang, J.A., Buchanan, A.K. and Hall, E.D. Temporal and spatial dynamics of Nrf2-ARE mediated gene targets in cortex and hippocampus following controlled cortical impact traumatic brain injury in mice.J. Neurotrauma 31: 1194-1201, 2014.
Miller, D.M., Singh, I.N., Wang, J.A. and Hall, E.D. Nrf2-ARE activator carnosic acid decreases mitochondrial damage, oxidative damage and cytoskeletal degradation following traumatic brain injury in mice. Exp. Neurol.264:103-110, 2015.
Cebak, J.E., Singh, I.N., Wang, J.A. and Hall, E.D. Phenelzine protects brain mitochondrial respiratory function from oxidative damage by scavenging lipid peroxidation-derived reactive carbonyls 4-hydroxynonenal and acrolein., Submitted.
Hall, E.D., Antioxidant Therapies for Acute Spinal Cord Injury. Neurotherapeutics 8:152-167, 2011. PMCID 3101837
Hall, E.D., Vaishnav, R.A. and Mustafa, A.G. Antioxidant Therapies for Traumatic Brain Injury. Neurotherapeutics 7:51-61, 2010. PMCID 2818465
Hall, E.D., Neurotherapeutics. Editorial. Neurotherapeutics 8:149-151, 2011. PMCID 3101834
Bains, M. and Hall, E.D. Antioxidant Therapies in Traumatic Brain & Spinal Cord Injury. Biochim. Biophys. Acta 1822:675-684, 2012.
Hall, E.D., Wang, J.A., Bosken, J.M. and Singh, I.N. Lipid Peroxidation in Brain or Spinal Cord Mitochondria After Injury. J. Bioenerg. & Biomemb., E pub ahead of print, Jan 18 2015.
Recent Book Chapters:
Hall, E.D. Acute Treatment Strategies for Spinal Cord Injury. Chapter 67 in: Spinal Cord Medicine: Principles and Practice (2nd Edition), (V.W. Lin et al, eds.), Demos Publishing Co., New York, pp. 883-896, 2010.
Hall, E.D. Overview of Therapeutics for TBI In: Nutrition and Traumatic Brain Injury: Improving Acute and Subacute Health Outcomes in Military Personnel, (J. Erdman, M. Oria and L. Pillsbury, eds), The National Academies Press, Washington, DC. pp.382-392, 2011.
Bosken, J.M., Wang, J.A. and Hall, E.D. Assessments of Oxidative Damage and Lipid Peroxidation After TBI/SCI. Chapter 32 In: Animal Models of Acute Neurological Injuries II: Injury and Mechanistic Assessments, J. Chen, X.C. Xu, X-M. Xu and J.H. Zheng (eds.), Humana Press, New York, pp 347-375, 2012.
Reier, P.J., M.A. Lane, E.D. Hall, Y.D. Teng and D.R. Howland. Translational Spinal Cord Injury Research: Preclinical Guidelines and Challenges. Chapter 30 in Handbook of Clinical Neurology 109:411-433, 2012., J. MacDonald and J. Verhagen,(eds.)
Hall, E.D. The Contributing Role of Lipid Peroxidation and Protein Oxidation in the Time Course of CNS Injury Neurodegeneration and Neuroprotection: An Overview. Chapter 21 in Brain Injury Principles: Molecular, Neuropsychological and Rehabilitation Aspects in Brain Injury Models, F. Kobeissy, (ed.). A volume in Methods in Molecular Biology series (Taylor and Francis Group, USA; CRC Press, Inc), pp. 49-60, 2015.
Hall, E.D. Translational Principles of Neuroprotective and Neurorestorative Therapy Testing in Animal Models of Traumatic Brain Injury. Chapter 11 in Translational Research in Traumatic Brain Injury, Frontiers in Neuroscience Series, G. Grant and D. Laskowitz (eds.), (Taylor and Francis Group), pp. 239-262, 2015.
Cebak, J.E., I.N. Singh, J.A. Wang, R.L. Hill, J.R. Kulbe and E. D. Hall. Carbonyl Scavenging as an Antioxidant Strategy for Acute Traumatic Brain Injury, in New Therapeutics for Traumatic Brain Injury: Prevention of Secondary Brain Damage and Enhancement of Repair and Regeneration, K.A. Heidenreich, (ed.) Elsevier, Inc., in press.
Yonutas, H.M., E.D. Hall and P.G. Sullivan. Therapeutic Targeting of Neuronal Mitochondria in Brain Injury. In: The Functions, Disease-Related Dysfunctions, and Therapeutic Targeting of Neuronal Mitochondria, V.K. Gribkoff, E.A. Jonas and J.M. Hardwick (eds.), Wiley Series on Neuropharmacology, (V.K. Gribkoff and L.K. Kaczmarek, Series Editors), Wiley, Inc., pp 359-377, 2016.
Hall, E.D. Neuroprotectants: Reactive Oxygen Species (ROS)-Based. Chapter 37 in: Primer on Cerebrovascular Diseases, Second Edition. L.R. Caplan, J. Billar, A.J. Thomas, E.H. Lo, M. Yenari and J.H. Zhang (eds.), Elsevier, Inc., in press.