DR. BRYAN HAINS
Bryan C. Hains, Ph.D., Assistant Professor of Neurology at Yale University School of Medicine, and staff scientist at the Center for Neuroscience and Regeneration at the VA Medical Center in West Haven, CT, was one of the four recipients of the Mike Utley Foundation 2007 Grant Awards. Dr. Hains, an accomplished researcher in the field of spinal cord injury and dysfunction, has authored over 35 peer-reviewed journal articles and books, and received numerous academic honors and awards for his work.
Dr. Hains’ research focus is on chronic neuropathic pain, mechanisms of secondary injury such as inflammation, loss or death of neurons after traumatic spinal cord injury, and the impact of such injury on paralysis and chronic pain. Dr. Hains also studies the application of cell–based therapies toward restoration of factors that help damaged neurons recover after spinal cord injury (SCI).
The Mike Utley Foundation’s 2007 Grant was awarded to Dr. Hains in support of his current research titled “Cortical Apoptosis and Motor Dysfuntion after SCI.” This research represents a highly innovative approach aimed at gaining a better understanding of how damage to the spinal cord results in neurological impairment, and is of high importance for the development of treatments for SCI. The proposed experiments will test the hypothesis that treatment with sodium channel blockers will reduce death of primary motor neurons in the brain, improve communication of motor commands to the spinal cord, and thus improve voluntary locomotor function after SCI.
SCI results in locomotor dysfuntion below the level of injury partly due to interruption of nerve circuits which transmit motor commands from the brain to the spinal cord. One prominent circuit, the corticospinal tract or CST, originates in the primary motor cortex region of the brain. Cell bodies of neurons of the CST send axons (nerve fibers) from the brain, down the length of the spinal cord, to make synaptic contact with spinal motor neurons that in turn drive functional groups of muscle motor units. The CST has been specifically implicated in the control of activities such as contact placing and skilled locomotor function.
Contusion to the spinal cord results in destruction of CST fibers and an irreparable loss of CST mediated function. One explanation for such irreparable loss of CST function is that a population of injured CST neurons dies after injury. Efforts to rescue damaged CST neurons from death may therefore offer hope for the improvement of motor recovery following SCI. Dr. Hains’ project will examine the effect of a sodium channel blocker called phenytoin on improvement of the electrophysiological function of CST neurons, motor behaviors associated with the CST, and reducing death of CST motor output neurons in the primary motor cortex following SCI.
Traditionally, treatments aimed at improving function after SCI have targeted the spinal cord. Dr. Hains’ focus on reducing SCI-induced motor neuron loss in the brain represents a highly innovative approach toward understanding cellular mechanisms underlying incomplete recovery of motor function and paralysis. This novel and timely study may have important treatment implications since phenytoin is generally regarded as safe, readily available, and currently used to treat a wide variety of human neurological conditions. We are very excited about the possibilities for this important research.
Rescue of Rat Spinal Cord Neurons from Death after Spinal Cord Injury
Hoechst 33342 (in blue, a nuclear stain), Fluorogold (in red, to mark injured neurons), and TUNEL (in green, identifies dying cells) triple labeling of spinal cord neurons 1 week after spinal cord injury. Hoechst staining of non-TUNEL-positive (arrows with tails) and TUNEL-positive (arrowheads) neurons with corresponding FG-backfilling are shown.
Spinal cord injured rats transplanted with olfactory ensheathing cells show fewer TUNEL-positive FG-backfilled neurons (B) when compared to rats that did not get the cell transplants (A). Olfactory ensheathing cells are known to secrete trophic factors that help injured neurons recover.
Quantitation of neurons that are both TUNEL- and FG-positive (C) reveals that OEC transplantation significantly (*P < 0.05) reduces apoptotic cell death at 1 wk. No
evidence of death was observed at any other time point. Scale bars = 125m in A, B; 20m in inset in A. Reference: Sasaki M, Hains BC, Lankford KL, Waxman SG, Kocsis JD. Protection of corticospinal tract neurons after dorsal spinal cord transection and engraftment of olfactory ensheathing cells. Glia. 2006 Mar; 53(4):352-9.