A FUNCTIONAL IN-VITRO MODEL FOR STUDYING THE CELLULAR AND MOLECULAR-BASIS OF SPINAL-CORD INJURY

Very little is understood about how spinal cord injury affects the mol ecular mechanisms responsible for generating locomotion. Recently, it has been shown in the spinal cord that the N-methyl-D-aspartate recept or, a specific class of excitatory amino acid receptors, plays a major role in the neurogenesis of locomotion. Paradoxically, studies of the brain and the spinal cord have shown that overactivation of this rece ptor can cause excitotoxicity and subsequent cell death. The ultimate goal of these experiments was to develop an isolated brain stem/spinal cord/hind limb preparation that would allow study of issues related t o excitotoxicity and the neurogenesis of locomotion. Findings indicate that: 1) exposure of the spinal cord to the excitatory amino acids pr oduced an alternating gate of the hind limbs; 2) application of N-meth yl-D-aspartate inhibitors were effective in preventing hind limb movem ent initiated by exposure to N-methyl-D-aspartate; 3) sensorimotor sti mulation of the tail produced hind limb movement that could be evoked for periods up to 8 hours; and 4) an excitotoxic event produced substa ntial loss of protein and possible osmotic changes. This study represe nts the first step in developing a powerful model for examining the ef fect of spinal cord injury on molecular mechanisms responsible for the neurogenesis of locomotion both at the brain stem, spinal motor gener ator, or sensorimotor level. The opportunity of observing hind limb mo vement in this preparation represents a powerful functional bioassay f or evaluating the extent of spinal cord injury.