**2. Paraplegia: mechanisms of degeneration**

SCI is included in two mechanisms: primary and secondary damage. When the direct physical injury to the spinal cord happened like any contusion, compression, contraction, and laceration, it can be called primary injury [46]. In this condition, axons separate from each other, mechanical injury to cells occurs directly, and blood vessels rupture. The progress of the injury site can occur in secondary phase, and it can be led to the restorative process [47]. This phase is including alterations in concentration of local ionic, blood pressure dysregulation (local and systemic), decrease of blood flow in the spine, disruption in the blood-brain barrier (BBB), diffusion of proteins from serum into the spinal cord, alterations in inflammatory chemokines and cytokines, cell apoptosis, excitotoxicity, activation of calpain proteases, accumulation of neurotransmitter, production of free radicals, lipid

#### *Mesenchymal Stem Cell Therapies for Paraplegia: Preclinical and Clinical Studies DOI: http://dx.doi.org/10.5772/intechopen.93249*

peroxidation, and activation of matrix metalloproteinases (MMPs). All of these changes can lead to demyelination of axons and also ischemia, necrosis, and apoptosis of spinal cord tissue [48]. As a result of these alterations, the inhibitory prospect overcomes, and axonal regrowth constrains. By this reason, injured axons cannot regenerate for a second time [49].
