**1. Introduction**

Intensive lifestyle brought about by the modern age of the twenty-first century often brings risks of trauma to the CNS. Both trauma of brain and spinal cord are considered not only as lifethreatening conditions, but also as substantial, social, and economic problems that affect mainly the young population. The increased incidence of trauma may be related to popular sports such as ice hockey, American football, rugby, horse riding, and diving, but the most common causes include traffic accidents [1]. Spinal cord trauma accounts for 70% of the total number of CNS injuries.

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

Understanding Molecular Pathology along Injured Spinal Cord Axis: Moving Frontiers…

http://dx.doi.org/10.5772/intechopen.72118

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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 regu-

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 sub-

In the CNS, immune cells acquire diverse phenotypes depending on the pathophysiology of

The inflammatory environment of injured spinal cord contains pro-inflammatory cytokines such as tumor necrosis factor α (TNFα), interleukins IL-1 and IL -6. Anti-inflammatory molecules, like transforming growth factor β1 (TGFβ) and IL-10, are released as well. Immune response in the CNS is mediated by resident microglia and astrocytes, which are innate immune cells with-

Among glial cells, microglia are firstly activated and are able to play a bifunctional role. They secrete toxic factors and contribute to tissue damage, but at the same time also release neuroprotective and neurotrophic molecules to allow tissue repair [11]. Interestingly, microglia and astrocytes are able to cross-talk with CNS-infiltrating immune cells, such as neutrophils,

**Neutrophils** are considered as the first inflammatory cells to arrive at the site of injury with a peak at 24 h after injury [12]. They are rapidly mobilized from the bone marrow in response to signals from pro-inflammatory CXC (CXCL8) family chemokines, IL- and cytokine-induced neutrophil chemoattractant 1 (CINC-1) to mediate pleiotropic functions in the immuneinflammatory response [13]. Neutrophils adhere to post-capillary venules 6–12 h post SCI and afterwards they migrate into the lesion site to phagocytose debris [14]. Neutrophils generate their own cytokines after stimulation by pro-inflammatory mediators and produce proteases

T cells, and other components of the innate immune system, as well as with neurons.

acute phase, but not at chronic phase when the formation of glial scar occurs.

of physiological functions below the site of injury.

lating microglial polarity remain unclear [9].

**2.1. Neuroinflammation**

the microenvironment.

out direct counterparts in the periphery.

Many spinal cord (SCI) patients remain permanently paralyzed with complete or partial loss of neurological functions below the site of injury [2]. The most common is paralysis of the body, usually affecting both lower limbs. At the same time, complications may arise when loss of sensitivity, urinary tract control, or the development of spasticity occur in the affected area [3]. Statistics shows that victims are twice as often men as women, with the highest occurrence of cases between the 19 and 40 years of age [4]. Care for patients with injured spinal cord is demanding and often requires lifelong financial costs [4].

The neurological outcomes depend on the range of damaged neuronal populations at the injury site, the level of disconnection of ascending and descending neuronal pathways, the secondary damage (edema, inflammation, and ischemia), and the age-dependent activation of regenerative processes (endogenous production of trophic factors and revascularization). Thus, patients with incomplete injury who retain some sensory or motor function below the lesion, undergo an extensive rehabilitation program to have a better chance of recovering some function. On the contrary, severe spinal cord injury causes a life-lasting disability for which currently no effective therapy is available. Another important factor is age; statistics shows that younger patients have better prognosis of recovery.

Therefore, the main objective of biomedical research is the development of new therapeutic procedures that would contribute to a more effective functional outcome and improvement of the quality of life.

In this chapter, we would like to highlight pathological consequences that could be evaluated by temporal and spatial proteomic analyses, leading to discrimination of the proteome within the entire spinal cord after acute injury. These data will be correlated with delivery of individual neuroprotective and combinatory neuroregenerative strategies for SCI treatment.
