a SciTechnol journal Research Article Journal of Spine & Neurosurgery All articles published in Journal of Spine & Neurosurgery are the property of SciTechnol, and is protected by copyright laws. Copyright © 2013, SciTechnol, All Rights Reserved. Ahmed et al., J Spine Neurosurg 2013, 2:3 http://dx.doi.org/10.4172/2325-9701.1000115 International Publisher of Science, Technology and Medicine Spinal Cord Injury-Induced Discharges Modify the Function of Glutamatergic System and Improve Ground and Skilled Locomotor Control Zaghloul Ahmed 1,3 *, Ahmed Hawash 3 and Andrzej Wieraszko 2,3 Abstract 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 frst 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 effux. 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 effciency 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 effciency 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 benefcial effects on functional recovery. Keywords Spinal cord; Injury-induced activity; Recovery; Lidocaine; Plasticity; Glutamate; Behaviour *Corresponding author: Zaghloul Ahmed, Associate Professor, Department of Physical Therapy, 2800 Victory Boulevard, Staten Island, NY10314, USA, E-mail: zaghloul.ahmed@csi.cuny.edu Received: February 22, 2013 Accepted: June 20, 2013 Published: June 24, 2013 Abbreviations AMPA: α-Amino-3-ydroxy-5-methyl-4-isoxazolepropionic acid; BMS: Basso muscle scale; CSI: Spinal cord injury; CNS: Central ner- vous system; D-Asp: 2,3 3 H-D-Aspartic acid; LTP: long-term poten- tiation; mCAP: Mechanically-induced compound action potential; NMDA: N-methyl –D-aspartic acid; VGCC: Voltage gated calcium channel Introduction Te injury of the spinal cord evokes intense neuronal activity of the spinal neurons. It has been always assumed that this excessive activity, correlated with a massive release of excitatory neurotransmitter, glutamate would impair functional recovery [1]. Tis assumption constituted a base for developing many pharmacological treatments for acute spinal cord injury (SCI) aimed at reduction of this hyperactivity. However, the idea of detrimental efects of hyperactivity is challenged by the data demonstrating that neuronal activity following injury may be benefcial for tissue regeneration [2] and functional recovery [3,4] activating intrinsic neuronal mechanism. It is well known that brief but intense activity in the nervous system may lead to long-lasting physiological and structural changes in neurons. Examples include long-lasting increase in synaptic efciency expressed as Long-Term Potentiating (LTP) [1], rapid changes of intrinsic neuronal excitability [5-10], enhanced sensitivity of postsynaptic membranes at individual synapses [11], and fnally an increase in the number of active synapses, silent prior to enhanced activity [8]. All these changes represent neuronal plasticity which has been recognized as the most important phenomenon involved not only in the mechanisms of memory [12], but also recently implicated as one of the processes contributing to recovery afer damage in the central nervous system (CNS) [13]. Te spinal cord injury-induced discharges propagate quickly along spinal nerves and were shown to be correlated with long-term alterations in the spinal neurons and modifcation of behaviour. Among others, an increase in the expression of Fos protein [14], the voltage gated calcium channel (VGCC) [15], and triggering of autotomy (self-injury) [1,16,17] have been reported. Although these discharges are routinely observed as spasms at the onset of SCI in animals, their quantifcation, characteristics, and their efects on behavioural recovery are rarely investigated. Most of spinal cord injuries are incomplete, sparing some functional connections [18] which could constitute anatomical substrate for functional recovery. We hypothesized that SCI by triggering an intense neuronal activity [15] would activate mechanisms involved in just described mechanisms of neuronal plasticity. Subsequently, the efcacy of spared connections between the injured spinal neurons would be enhanced initiating long-term processes leading ultimately to a better recovery. In order to evaluate the role of neuronal activity in the recovery process we compared the efects of spinal cord injury in animals, or in the tissue from the animals expressing injury-induced activity with the preparations where post-injury activity was attenuated by application of lidocaine.