Neuroprotective effects of gacyclidine after experimental photochemical spinal cord lesion in adult rats: Dose-window and time-window effects

The aim of this study was to evaluate the efficacy, optimal dose, and optim al time-window of gacyclidine, a novel N-methyl-D-aspartate (NMDA) receptor antagonist, in terms of its functional, histopathological, and electrophys iological effects after experimental spinal cord injury. The spinal cord of rats was damaged by a photochemical method and the animals were treated by saline or gacyclidine at doses of 1, 2.5, or 5 mg/kg 10 min after injury o r gacyclidine 1 mg/kg 10, 30, 60, and 120 min after injury. The time-course of the motor score (walking and inclined-plane stability) was evaluated un til day 18, and somatosensory evoked potentials were determined on day 18. The animals were then sacrificed, and the cross-sectional area of the spina l cord (at the epicenter of the injury, above and below the injury) was mea sured. Walking recovery was better in most of the groups treated after inju ry than in the untreated injured animals. Motor performances were related t o preservation of a larger undamaged area of spinal cord at the level of th e injury and, interestingly, with prevention of extension of the anatomical lesion above the level of the injury. Somatosensory evoked potential ampli tudes were often higher in treated groups. These results confirm that gacyc lidine induces dose-dependent and time-dependent attenuation of spinal cord damage after an experimental vascular lesion. Although all three doses ind uced neuroprotective effects, recovery was greater and very homogeneous in the group treated with 1 mg/kg. Moreover, recovery was slightly better and more homogeneous within the groups treated 10 and 30 min after injury compa red to the other groups. It appears that, according to the existing evidenc e, NMDA antagonists are an essential component in the elaboration of a neur oprotective strategy after spinal cord trauma.