Axon Biology & Nerve Regeneration
Dr. Peter StysFaculty of Medicine PubMed
Dr. Stys is a neurologist/neuroscientist and a world leader in the detailed study of pathophysiological mechanisms of white matter injury in stroke and trauma. He has extensive expertise in electrophysiological recording methods in myelinated axons and his team has recently developed confocal, multiphoton and coherent anti-Stokes Raman scattering (CARS) imaging techniques for both fixed immunostained and live myelinated axons and glial cells.
Dr. Stys’ team discovered several novel injury mechanisms responsible for axo-glial damage in ischemia/trauma: Ca overload secondary to reverse Na-Ca exchange (Stys et al., J Neurosci, 1992) and glutamate excitotoxicty due to reversal of Na-dependent glutamate transport in damaged spinal axons (Li and Stys, J Neurosci, 1999). This endogenously released glutamate then activates newly discovered AMPA/kainate receptors on axons (Ouardouz et al., J Physiol, 2006), and surprisingly, NMDA receptors on oligodendrocytes and the myelin sheath itself (Micu et al., Nature, 2006). In addition, depolarization of damaged fibers leads to release of toxic amounts of Ca from intra-axonal Ca stores, dependent on L-type Ca channels and ryanodine receptors (Ouardouz et al., Neuron, 2003), via a mechanism very similar to excitation-contraction coupling in muscle cells. The various signaling molecules (glutamate receptors, Ca channels, nNOS, RyRs, and likely many others) are organized along the internodal axolemma under the myelin sheath in discrete “axonal nanocomplexes”, very reminiscent of arrangements at the post-synaptic membrane of conventional interneuronal synapses.
Dr. Stys' insights provide a rational basis for devising drug therapy for the acute phases of stroke, spinal cord injury, brain trauma, and neuroinflammatory conditions such as EAE/MS in which axons, oligodendrocytes and myelin are prominent targets of damage.
In his current research Dr. Stys aims to develop even more advanced imaging technologies to study axo-glial interactions under physiological and pathological conditions.