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 molecular mechanisms responsible for generating locomotion. Recently, it has been shown in the spinal cord that the N-methyl-D-aspartate receptor, 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 overeactivation of this receptor 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 to excitotoxicity and the neurogenesis of locomotion. Findings indicate that: 1) exposure of the spinal cord to the excitatory amino acids produced an alternating gate of the hind limbs; 2) application of N-methyl-D-aspartate inhibitors were effective in preventing hind limb movement initiated by exposure to N-methyl-D-aspartate; 3) sensorimotor stimulation of the tail produced hind limb movement that could be evoked for periods up to 8 hours; and 4) an excitotoxic event produced substantial loss of protein and possible osmotic changes. This study represents the first step in developing a powerful model for examining the effect of spinal cord injury on molecular mechanisms responsible for the neurogenesis of locomotion both at the brain stem, spinal motor generator, or sensorimotor level. The opportunity of observing hind limb movement in this preparation represents a powerful functional bioassay for evaluating the extent of spinal cord injury.
Takeda
H
H
Department of Orthopaedics, College of Medicine, University of California, Irvine.
Caiozzo
V J
VJ
Gardner
V O
VO
D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000502:physiology; D016923:Cell Death; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006614:Hindlimb / Q000294:innervation; D008124:Locomotion / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000737:chemistry* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology*
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate