Neuroprotective effects of a novel NMDA antagonist, Gacyclidine, after experimental contusive spinal cord injury in adult rats

The aim of this study was to analyze the optimal time-window for neuroprote ction by a novel NMDA antagonist, Gacyclidine, after experimental spinal co rd injury, in terms of its functional, histopathological and electrophysiol ogical effects. This molecule has already demonstrated its capacity for red ucing the extent of an ischemic lesion and is currently experimented in a c linical trial of spinal cord injury. In this study, the spinal cord of rats was damaged by a contusive method and the animals were treated by saline o r 1 mg/kg of Gacyclidine i.v., 10, 30, 60 and 120 min after injury. The tim e-course of the motor score was evaluated on days 1, 7 and 18 after injury, and somatosensory evoked potentials were determined on day 20. The animals were then killed and the cross-sectional area of the spinal cord (at the e picenter of the injury, above and below the injury), was measured. Walking recovery was better (P<0.0125) in the group treated 10 min after injury tha n in the untreated injured animals after 18 days of injury. Motor performan ces were related to the preservation of a larger undamaged area of spinal c ord at the level of the injury (P<0.0125). Somatosensory evoked potential a mplitudes were also higher in this group. These results confirm that Gacycl idine attenuates spinal cord damage after an experimental spinal cord lesio n. Recovery was better within the group treated 10 min after injury compare d with the other groups, which certainly confirms that the acute time-cours e of glutamate release requires rapid pharmacological intervention to achie ve good results. (C) 2000 Elsevier Science B.V. All rights reserved.