Fig. 1

An overview of local spinal cord injury (SCI) pathogenesis. Generally, an initial trauma (primary injury) leads to immediate hemorrhage and cell death at the impact site, mainly affecting neurons and OLs. This initiates a secondary injury cascade. Although secondary injury aims to ameliorate primary injury and limit its progression, it frequently contributes to extending the damage after primary SCI, promoting further cell death, tissue loss and progressive dysfunction. Immune and glial cells are central members involved in secondary injury after SCI. First, neutrophils are recruited to the damage site in response to primary injury, leading to augmented cytokine, protease and ROS production. This activates resident macrophages and microglia, whereas monocyte recruitment from systemic circulation is also stimulated, leading to a maximum peak of macrophages 3 d postinjury. Both macrophages and microglia can polarize into M1 (proinflammatory) and M2 (anti-inflammatory) phenotypes. An exacerbated M1 polarization in both cell types favors an inflammatory environment and the related oxidative damage, which contributes to the secondary mechanisms of injury. On the other hand, astrocytes are involved in glial scar formation (from the subacute stage), limiting the spread of injury and inhibiting axonal growth, thus driving demyelination and neurotransmitter accumulation. Excessive glutamate accumulation triggers a phenomenon called glutamate excitotoxicity, a central mechanism of secondary damage after SCI. Adaptive immune cells (T and B cells) are later recruited to the injured spinal cord. T lymphocytes are activated due to the proinflammatory environment, cell damage and autoantigen presentation (a common event that occurs after SCI). This favors the production of autoantibodies by B cells, leading to an autoimmune response related to SCI. Other critical mechanisms related to SCI are BSCB dysfunction, ischemia, edema and necrotic cell death related to primary and secondary injury. IL-1β Interleukin-1β; IL-6 Interleukin-6; TNF Tumor necrosis factor; CNS Central nervous system; ROS Reactive oxygen species; OLs Oligodendrocytes; BSCB Blood–spinal cord barrier; CTLs Cytotoxic lymphocytes