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Clinical Neuroengineering
Spinal Cord Injury Treatment & Basic Research
 Abstract
Initial trauma to the spinal cord triggers a series of complex pathophysiological mechanisms leading to physiological, behavioral and pathological degradation. This results in spreading of injury from the direct impact site to surrounding regions, causing delayed secondary degeneration and gross morphological changes such as leukocyte infiltration, neuronal death, and axonal degeneration. This delayed secondary degeneration, originating from the central canal, spreads to surrounding gray and white matter regions over hours, days, or weeks after injury.

There has been some recent interest in the use of therapeutic hypothermia to aid recovery of spinal cord structure and function. Although there have been behavioral investigations to measure the neuroprotective benefits of hypothermia, these have not produced conclusive results. Therefore, we investigate the effect of hypothermia using quantitative somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) monitoring and analysis.
 
Rats that received therapeutic hypothermia after injury had an increased SEP N1-P2 amplitude (left) and reduced N1 latency (right) compared to injured rats with normal body temperature.
 
Recent studies have also indicated that spinal cord injury is accompanied by chronic progressive demyelination. The limited regenerative capacity of the adult CNS has directed the focus of preclinical trauma research on means of reducing secondary degeneration and promoting regeneration. Neural stem cells could potentially address both of these needs by promoting survival of host tissue, growth of host tissue, and/or replacement of cells lost as a result of trauma. We are investigating the effect of transplanted embryonic stem cell-derived immature and mature oligodendrocytes after spinal cord injury using novel SEP/MEP monitoring tools in conjunction with behavioral and histological examination.
 
Thee survival of ESC-derived neural progenitors cells are shown at 1h (right) and 18h (left, middle) after injection into T7 and T9 following 12.5 mm contusion injury in spinal cord T8.
 
Researchers
Angelo H. All, MD, MBA
Gracee Agrawal
Chris Lee
 
Collaborators
Jeff Bulte, PhD - Johns Hopkins School of Medicine (Radiology)
Candace Kerr, PhD - Johns Hopkins School of Medicine (Institute of Cell Engineering)
Douglas Kerr, MD, PhD - Johns Hopkins School of Medicine (Neurology)
Richard Skolasky, PhD - Johns Hopkins School of Medicine (Orthopedic Surgery/Statistics)
Piotr Walczak, MD - Johns Hopkins School of Medicine (Radiology)
 
Funding
Maryland Stem Cell Research Fund (TEDCO)
Johns Hopkins RESTORE Fund
 
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