Kainate-mediated excitotoxicity induces synaptic transmission dysfunction with block of locomotor networks even in the absence of extensive motoneuron damage in the rat spinal cord in vitro

The role of excitoxicity in producing neuronal damage following spinal injury was investigated by studying the effects of kainate (1 h) on the isolated spinal cord of newborn rats. Kainate (1 mM) induced a large and persistent depolarization of all ventral roots (VRs) accompanied by transient oscillatory alternating cycles. On intracellularly recorded motoneurons kainate evoked strong depolarization, temporary spiking and electrode disimpalement that prevented continuous cell monitoring. After 1 h washout, reimpaled motoneurons showed normal resting membrane potential and input resistance with full antidromic spike, suggesting only short-lived alterations in motoneuron function without irreversible damage. Consistent with this view was the full recovery of the kainate-suppressed motoneuron field potential evoked by antidromic VR stimulation. Histological examination showed neuronal loss affecting only 12 % of cells in the ventral horn region and predominantly distributed to the central grey matter without apparent discrimination between neurons and glia. Unlike motoneuron activity, polysynaptic transmission to motoneurons was strongly decreased by kainate, could not be reinstated even with 10 time larger stimuli and remained dramatically depressed after 24 h washout. Thus, synaptic transmission impairment appeared to be a contributor to spinal deficit more important than loss of neurons and motoneurons. In conclusion, a strong excitotoxic insult, as the one elicited by kainate, did not produce global damage to spinal cells and circuits, indicating a gradient of sensitivity to excitotoxicity. This observation suggests that mere excitotoxicity (even if accompanied by intense depolarization) was inadequate to generate directly or indirectly extensive spinal lesion and that other sources of damage are likely to contribute to the persistent functional deficit observed after spinal injury.