Spinal cord injury (SCI) most frequently occurs as a result of trauma, primarily from motor vehicle accidents and falls, as well as from gunshot injuries [Citation1,Citation2]. In the year 2013, US estimates suggest that approximately 12,000 new cases of SCI occur each year, while the prevalence may be as high as 265,000 individuals [Citation2]. It is important that any research that investigates the possible pharmaceutical agents action on the traumatized spinal cord is relevant and of major importance for physicians since SCI occurs mainly among males (80.7%) and the average age at injury is 40.7 years [Citation2], an age of high productivity.
However, there is still no significant progress in the research for treatment methods targeting to improve biological repair of the cord and final neurologic recovery following SCI. Although the main mechanism of secondary SCI remains unknown, it is thought that early inflammatory response of the spinal cord to acute injury triggers secondary tissue injury [Citation3].
NASCIS-1 (National Acute Spinal Cord Injury Study), NASCIS-2, and NASCIS-3 studies have shown that a high dose of Methylprednisolone has beneficial effects on SCI. Although there is debate on the therapeutic effect of Methylprednisolone in recent studies, high dose systemic Methylprednisolone remains the only treatment option for spinal cord injury [Citation4,Citation5]. Methylprednisolone acts by preserving the integrity of the structure and functions of biologic membranes through inhibition of lipid peroxidation occurring after SCI, however, it has been reported that it has no effect on tissue regeneration and functional restoration of damaged tissue. Furthermore, by stabilizing the flow of intra- and extracellular Calcium it helps in the reformation of the acid–base balance of the cell.
Moreover, increasing the blood flow of the spinal cord with high doses of Methylprednisolone enhances the reformation of the Na+/K+ ATPase activity, reduces the retention of sodium and water at the site of lesion, prevents potassium loss and reduces neurologic loss [Citation4].
Levetirasetam, is an antiepileptic agent that works by partially closing the N-type high voltage Calcium channels thereby reducing intracellular Calcium levels, and partially reversing the reduced flow regulated by gamma aminobutyric acid (GABA) and Glysine (Glycine is one of the proteinogenic amino acids) [Citation6]. Moreover, the neuroprotective effect of Levetirasetam and the capability of significantly reducing the effects of brain damage in experimental models, and the reduction of lipid peroxidation and oxidative stress as well as preventing apoptosis has been reported [Citation7,Citation8].
Despite advances in spinal instrumentation and surgical techniques, no significant improvement has been identified in the neurological recovery following acute trauma and associated SCI. In this animal investigation in rats, the authors studied the potential therapeutic effects of Levetiracetam compared to Methylprednisolone on SCI in acute and subacute period model [Citation9].
A wide Th5-Th8 laminectomy was made and subsequently using a vascular aneurysm the authors temporarily compressed the thoracic spinal cord to induce SCI. Three groups of animals were compared: 1) SHAM-A group (SCI without pharmacologic agent administration; 2) MP-A group (SCI and a single dose 30 mg/kg Methylprednisolone was administered intraperitoneally; and 3) LV-A group (SCI model and a single dose Levetirasetam 5 mg/kg was administered intraperitoneally. In the control group there was no SCI.
Following that, the damaged thoracic spinal cord was resected and examined both histopathologically and biochemically. The levels of “bleeding severity” and “vacuolization” and the “necrotic neurons” occurring in the SCI were determined. Tissue healing levels were examined in MTS-applied specimens. Toluidine blue axonal injury severity (fragmentation, degeneration and swelling) of the subacute period was evaluated.
The tissues for biochemical analysis were immediately stored frozen at −80 °C. Subsequently, in order to examine the levels of malondialdehyde, insulin-like growth factor-1 beta, interferon-gamma, superoxide dismutase, total nitrite/nitrate, and tumor necrosis factor-alpha in the injured tissues, the tissues were homogenized.
The methods used for histopathological and biomechanical investigation are well established and appropriate for this investigation. The statistical methods used to compare the parameters within different groups of rats are appropriate. The minimum number of 42 experimental animals needed in the study to allow for statistical analysis was used.
The authors showed that both Methylprednisolone and Levetiracetam improved the histopathological architecture within the damaged spinal cord during only the acute period of SCI, but they could not improve it in the subacute period. Additionally, both pharmacological agents affected biochemical parameters in both acute and subacute stages of SCI. However, the authors did not find that the administration of any of the two pharmacological agents (Methylprednisolone and Levetiracetam) had any effect on biochemical data in both acute and subacute periods.
There are several limitations in this study. First, this study included acute and subacute periods of SCI but not from the chronic process. Second, detailed histopathological and biochemical analysis methods were not used to demonstrate the curative effect of pharmacological agents used in experiment due to technical and financial problems. Third, the tests for investigation of the functional recovery were not applied to the subjects in the experimental groups for the reason that the specified experiment time was short. Fourth, it was not possible to perform tests (such as MRI) to obtain radiological figures of the SCI due to the small body size and dimensions of the subjects.
I believe that this study is the first one that investigates the effect of Levetiracetam in Spinal cord injury. I strongly believe that more studies are needed to shed more light in the treatment of SCI in the acute phase.
DECLARATION OF INTEREST
The author(s) report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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