Daniel Marsh PhD
Phone:
902-494-3934 (office)
902-494-7845 (lab)
Email: daniel.marsh@dal.ca

Inflammation, Repair and Regenerative Strategies
After Traumatic Injury.

Spinal Cord

Traumatic spinal cord injury is often associated with secondary injury processes that expand the extent of the initial injury and results in a greater negative impact on neurological outcomes. Inflammation and the invasion of the spinal cord by macrophages and neutrophils are key components of secondary injury and enter into a self-perpetuating cycle of tissue destruction that includes the release of free radicals, proteases, chemokines, cytokines and prostaglandin. My research is focused on trying to limit the infiltration and activation of inflammatory cells into the spinal cord after injury.  Acute reductions in the numbers of neutrophils and macrophages present in the spinal cord after injury is associated with enhanced sparing of white and gray matter and improved sensory, motor, and autonomic neurological outcomes.  Strategies that promote neuroprotection, tissue sparing and decreased secondary damage are important because a relatively few descending bulbospinal axonal tracts are sufficient to provide regulatory inputs and improve control of blood pressure and bladder function – greatly enhancing quality of life.  A condition called autonomic dysreflexia develops in most patients after an upper thoracic or cervical spinal cord injury. This condition is characterized by symptoms that include episodic hypertension, severe headache, profuse sweating, cardiac arrhythmias and hemorrhagic stroke.  I am currently employing experiments using mild, moderate and severe degrees of spinal cord injury to study the relationships among blood pressure, bladder function, autonomic dysreflexia, and sparing of serotonergic bulbo-spinal axons.


Skeletal Muscle

Skeletal muscle injuries resulting from trauma, surgery, and overuse are a common and often debilitating problem.  Complete regeneration of tissue and recovery of function do not always occur, and muscle is often replaced with fibrotic connective tissue or adipose.  In the presence of oxidative stress, free radicals, and cytokines, inflammatory responses are generally more destructive and prone toward scar formation.  The objective of my research is to investigate mechanisms which contribute to inadequate regeneration of skeletal muscle and enhance fibrotic scar formation in rats after age-induced chronic oxidative stress and in rats after ischemia-induced acute oxidative stress.

Research Support

Heart and Stroke Foundation of Nova Scotia
Nova Scotia Health Research Foundation
Canadian Foundation for Innovation
Natural Sciences and Engineering Research Council (NSERC)

Graduate Students

Christen Cormier
Jason Meisner

Technical Personnel

Melanie Wilcox

Selected Publications

1. Weaver, L. C., D. R. Marsh , D. Gris, A. Brown, and G. A. Dekaban.  Autonomic dysreflexia after spinal cord injury: central mechanisms and strategies for prevention. Prog. Brain Res. 152: 245-63, 2005.
2. Gris, D., D. R. Marsh, G. A. Dekaban and L. C. Weaver.  Comparison of effects of methylprednisolone and anti-CD11d antibody treatments on autonomic dysreflexia after spinal cord injury.  Exp. Neurol. 194: 541-549, 2005.
3. Gris, D., D. R. Marsh, M. A. Oatway , Y. Chen, E. F. Hamilton, G. A. Dekaban and L. C. Weaver.  Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function.  J. Neurosci. 24: 4043-4051, 2004.
4. Marsh, D. R., and L. C. Weaver.  Autonomic dysreflexia, induced by noxious or innocuous stimulation, does not depend on changes in dorsal horn substance P.  J. Neurotrauma. 21: 817-828, 2004.
5. Marsh, D. R., S.T. Wong, S. O. Meakin, J. I. S. MacDonald, E. F. Hamilton, and L. C. Weaver. Neutralizing intraspinal NGF with a trkA-IgG fusion protein blocks development of autonomic dysreflexia in a clip-compression model of spinal cord injury. J. Neurotrauma. 19:1531-1540, 2002.
6. Weaver L. C., D. R. Marsh, D. Gris, S. O. Meakin, and G. A. Dekaban.  Central mechanisms for autonomic dysreflexia after spinal cord injury.  Prog Brain Res. 137:83-95, 2002.
7. Marsh, D. R., K. D. Holmes, L. C. Weaver and G. A. Dekaban. Distribution of an NMDA receptor-GFP fusion protein in sensory neurons is altered by a C-terminal construct.  J. Neurochem. 77: 24-35, 2001.