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 neuroprotection by a novel NMDA antagonist, Gacyclidine, after experimental spinal cord injury, in terms of its functional, histopathological and electrophysiological effects. This molecule has already demonstrated its capacity for reducing the extent of an ischemic lesion and is currently experimented in a clinical 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 or 1 mg/kg of Gacyclidine i.v., 10, 30, 60 and 120 min after injury. The time-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 epicenter 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 than in the untreated injured animals after 18 days of injury. Motor performances were related to the preservation of a larger undamaged area of spinal cord at the level of the injury (P<0.0125). Somatosensory evoked potential amplitudes were also higher in this group. These results confirm that Gacyclidine attenuates spinal cord damage after an experimental spinal cord lesion. Recovery was better within the group treated 10 min after injury compared with the other groups, which certainly confirms that the acute time-course of glutamate release requires rapid pharmacological intervention to achieve good results.
Gaviria
M
M
Centre PROPARA, Laboratoire de Neurophysiologie Clinique et Laboratoire de Chirurgie Fonctionnelle Expérimentale, Parc Euromédecine, 34195, Montpellier, France. mgaviria@club-internet.fr
Privat
A
A
d'Arbigny
P
P
Kamenka
J
J
Haton
H
H
Ohanna
F
F
D000818:Animals; D003288:Contusions / Q000188:drug therapy*; D003510:Cyclohexanes / Q000494:pharmacology*; D053138:Cyclohexenes; D004594:Electrophysiology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D015430:Weight Gain
D003510:Cyclohexanes; D053138:Cyclohexenes; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D010880:Piperidines; D016202:N-Methylaspartate; C070707:gacyclidine