Abstract

Purpose: To compare the effect of bethanechol versus selegiline in ameliorating spinal cord injury (SCI) in a rat model.Methods: Male adult Wistar rats (200 – 250 g) were equally divided into 3 groups: test (SCI rats treated with bethanechol), and control reference (SCI rats treated with selegiline) and control (SCI rats treated with vehicle). SCI was induced in the rats using the clipping method. Thereafter, motor function was assessed in the rats using a rotarod. Each rat was sacrificed by decapitation, and the cortex was excised for use in the study of the involvement of cholinergic and monoaminergic transmission in SCI rats using real-time quantitative polymerase chain reaction and western blot analysis.Results: Retention time was numerically greater in rats treated with acetyl choline agonist at all rotations (10, 15 and 25 rpm) when compared to MAO A inhibitor group, but the difference was not statistically significant (p > 0.05). Both bethanechol and selegiline improved motor function by increasing cholinergic and monoaminergic transmission. Both drugs (bethanechol and selegiline) were effective in ameliorating the motor function deficit caused by spinal cord injury. A significant upregulation in acetylcholine esterase (AChE) was observed in the cortex of the SCI rats, relative to non-SCI rats (p < 0.005). Results from cholinergic receptor binding studies revealed significantly decreased Bmax and kd values for muscarinic receptors in SCI rats, when compared to non-SCI rats. Moreover, the reduction in the intensity of cholinergic receptors was significantly higher in the cerebral cortex of SCI rats than in non-SCI rats.Conclusion: Bethanechol and selegiline are effective in ameliorating motor function deficit caused by spinal cord injury in rats. Both drugs also improve motor function in SCI rats. Therefore, the drugs have potentials for use in the therapeutical management of spinal cord injury.
 Keywords: Spinal cord injury, Bethanechol, Selegiline, Motor functions, Monoaminergic transmission, Cholinergic transmission

Highlights

  • Spinal cord injury (SCI) is one of most common reasons for disability worldwide

  • The present preclinical investigation is the first study to compare the effect of bethanechol with selegiline in amelioration of spinal cord injury in rat model of spinal cord injury to confirm whether targeting central nervous system pathway – cholinergic or monoaminergic helps in recovering motor functions after spinal cord injury

  • The results of current study showed that the bethanechol was more effective when compared to selegiline in improving motor function and promoting recovery of spinal cord injury (SCI)

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Summary

INTRODUCTION

Spinal cord injury (SCI) is one of most common reasons for disability worldwide. understanding CNS pathways after SCI is a key to establishing an accurate treatment [1]. It was hypothesized that inhibition of monoamine oxidase-B may improve the SCI recovery by increasing level of NA and 5 HT in brain or spinal cord area. Hypothesized that activation of muscarinic receptor in brain and spinal cord may improve recovery of SCI by increasing cholinergic transmission in CNS. The present study was designed to compare the effect of Bethanechol versus Selegiline in amelioration of spinal cord injury (SCI) in a rat model. Comparison of retention times, locomotor function score, pain threshold and the expressions of cholinergic and monoamine oxidase receptors in cortical region between both groups were analyzed using appropriate statistical method such as student t-test. Data related to receptor binding analysis in cortex between both groups were analyzed using nonparametric test.

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