Spinal Cord Injury-Induced Discharges Modify the Function of Glutamatergic System and Improve Ground and Skilled Locomotor Control

Background: Recent data demonstrate that enhanced activity, induced by spinal cord injury (SCI) may accelerate functional recovery. This study was design to verify this assumption. Methods: The effects of spinal cord injury with or without pharmacological suppression of injury-induced activity were investigated. In vivo method tested weekly locomotor activity of the animals during 7-week post-injury period. In vitro techniques characterized neuronal activity and properties of glutamatergic system. Results: The sciatic nerve activity during SCI was categorized into sequentially occurring phases. The first phase, represented by mechanically-induced compound action potential, was followed by the second phase of high frequency discharges lasting approximately 2 min. These two phases were accompanied by enhanced glutamate efflux. The third phase lasting about 15 min with no discharges was followed by a hyperactive fourth phase with spasms and increased spontaneous activity. The application of lidocaine over the spinal cord before injury attenuated phasic activity. The ability of glutamatergic system to release glutamate in vitro 2 h, 24 h, and three weeks after the injury (chronic stage) from animals treated, or not treated with lidocaine was reduced, or elevated, respectively. The efficiency of glutamate uptake system in the animals not treated with lidocaine was elevated 2 h after injury and diminished later. In animals treated with lidocaine, the decline in the efficiency of glutamatergic system 2 h after the injury was followed by an increase. The expression of glutamatergic AMPA receptors in lidocaine-treated animals continued to rise from 2 h after the injury through a chronic stage. The expression of AMPA receptors in animals not treated with lidocaine was attenuated 2 and 24 h after the injury but elevated in the chronic stage. Blocking injury-induced activity with lidocaine impaired locomotion recovery. Conclusion: Neural discharges following the onset of SCI have beneficial effects on functional recovery.