Monoamine oxidase-B inhibitor protects degenerating spinal neurons, enhances nerve regeneration and functional recovery in sciatic nerve crush injury model

摘要

Abstract Monoamine oxidase-B (MAOB), a flavin adenine dinucleotide (FAD), is an enzyme which catalyzes the oxidation of amines. MAOB is proposed to play a major role in the pathogenesis of neurodegeneration through the production of reactive oxygen species (ROS) and neurotoxins. The present study was designed to outline the effects of the MAOB inhibitor (MAOB-I) on neuroprotection of spinal neurons, regeneration of sciatic nerve fibers, and recovery of sensory-motor functions in the sciatic nerve crush injury model. Male Wistar rats (4-months-old) were assigned to i) Na?ve (N), ii) Sham (S), iii) Sciatic nerve crush and treated with saline (CRUSH?+?SALINE) and iv) Sciatic nerve crush and treated with MAOB inhibitor (CRUSH?+?MAOB-I) groups (n?=?10/group). In groups iii and iv, the crush injury was produced by crushing the sciatic nerve followed by treatment with saline or MAOB-I (Selegiline ? 2.5?mg/kg) intraperitoneally for 10 days. Behavioral tests were conducted from week 1 to week 6. At the end of the study, sciatic nerve and lumbar spinal cord were examined by immunohistochemistry, light and electron microscopy. MAOB-I treatment showed significant improvement in sensory and motor functions compared to saline treatment (p? Highlights ? MAOB-I treatment produced significant motor deficits reduction post nerve injury. ? Crush nerve?+?MAOB-I animals showed significant decrease in nociception parameters. ? MAOB-I treatment showed significant axonal regeneration and neuronal protection. ? MAOB-I treatment resulted in an increase in myelin basic protein in injured-nerve. ? MAOB-I presented neuroprotective and axonal regenerative effects post nerve injury.