nderstanding the pathophysiological changes triggered by an acute spinal cord injury is
a primary goal to prevent and treat chronic disability with a mechanism-based approach.
After the primary phase of rapid cell death at the injury site, secondary damage occurs
via autodestruction of unscathed tissue through complex cell-death mechanisms that
comprise caspase-dependent and caspase-independent pathways. To devise novel neu-
roprotective strategies to restore locomotion, it is, therefore, necessary to focus on the
death mechanisms of neurons and glia within spinal locomotor networks.To this end, the
availability of
in vitro
preparations of the rodent spinal cord capable of expressing locomotor-
like oscillatory patterns recorded electrophysiologically from motoneuron pools offers the
novel opportunity to correlate locomotor network function with molecular and histological
changes long after an acute experimental lesion. Distinct forms of damage to the
in vitro
spinal cord, namely excitotoxic stimulation or severe metabolic perturbation (with oxidative
stress, hypoxia/aglycemia), can be applied with differential outcome in terms of cell types
and functional loss. In either case, cell death is a delayed phenomenon developing over
several hours. Neurons are more vulnerable to excitotoxicity and more resistant to meta-
bolic perturbation, while the opposite holds true for glia. Neurons mainly die because of
hyperactivation of poly(ADP-ribose) polymerase-1 (PARP-1) with subsequent DNA damage
and mitochondrial energy collapse. Conversely, glial cells die predominantly by apoptosis.
It is likely that early neuroprotection against acute spinal injury may require tailor-made
drugs targeted to specific cell-death processes of certain cell types within the locomotor
circuitry. Furthermore, comparison of network size and function before and after graded
injury provides an estimate of the minimal network membership to express the locom
