**2. Pathology**

Spinal cord trauma triggers a pathophysiological complex of cellular and molecular reactions leading to edema, hemorrhage, free radical formation, glutamate excitotoxicity, ischemia, macrophage phagocytic activation, glial scar formation, and apoptotic changes in the injured tissue [5]. These processes take place within a few minutes to weeks and years after the injury. During this time, under the influence of secondary events, small primary damage will spread to the surrounding healthy area within the craniocaudal axis, causing partial or complete loss of physiological functions below the site of injury.

One of the key events of secondary processes is inflammation characterized by fluid accumulation (edema) and the recruitment of immune cells (neutrophils, T-cells, macrophages, and monocytes) [6]. In fact, spinal cord microglial cells normally function as a kind of reactive immune cells that begin to respond to signals after pathological stimuli (injury, infection, or tumors) [7] and are activated at the lesion epicenter [8]. It has been suggested that microglia/ macrophages can be polarized into M1-neurotoxic or M2-neuroprotective states and produce a variety of cytokines, chemokines, and neurotrophic factors. However, the mechanisms regulating microglial polarity remain unclear [9].

In addition, not only stimulated microglia/macrophages but also astrocytes, meningeal cells, and fibroblasts together with the increased production of inhibitory chondroitin sulfate proteoglycans (CSPGs) are involved in the spinal cord pathogenesis [10]. Macrophages can alter their phenotypes and functions according to changes in the spinal cord microenvironment during subacute and chronic phases. Thus, SCI triggers an excessive inflammatory response mediated by the invasion of M1/M2 macrophages into and around the central lesion at subacute phase, but not at chronic phase when the formation of glial scar occurs.
