Epigallocatechin-3-gallate treatment to promote neuroprotection and functional recovery after nervous system injury

Traumatic spinal cord injury (SCI) causes motor paralysis, sensory anesthesia and autonomic dysfunction below the lesion site and additionally some SCI patients refer neuropathic pain together with these signs and symptoms. Clinical and experimental studies have revealed the main pathological changes of injured spinal cord implicated in all these signs and symptoms, including neuropathic pain. After few hours of traumatic SCI, it is usual to observe broken blood brain barrier with plasma and blood cells extravasation, cell necrosis, disruption of ascending and descending spinal cord pathways and increased potassium and glutamate. Glutamate contributes to excitotoxicity of neurons whereas potassium facilitates ectopic depolarization of survival neurons and activation of resident microglia. Reactive microglia cells are able to secrete several pro-inflammatory cytokines (e.g., tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), IL-6) and chemokines (C-C motif) ligand 2 (CCL2) or monocyte chemoattractant protein 1 (MCP1) that contribute to the reactivation and migration of more microglial cells located far to lesion site, and also astrocytes that contribute to the secretion of more pro-inflammatory agents. Chemokine attracts blood cells, including neutrophils, lymphocytes and monocytes that infiltrate on injured spinal cord parenchyma, and contribute to eliminate the cellular debris, but also secrete more pro-inflammatory agents. All these cellular and biochemical changes were observed during the first weeks post-injury. Finally, reactive astrocytes and microglial cells form the glial scar around the lesion site, and astrocytes secrete several proteoglycan that inhibit the re-growth of regenerated central axons across the lesion site. Apoptosis of oligodendrocytes, and wallerian degeneration of nude axons also were seen. The associated myelin proteins (e.g., NOGO, OMpG, MAG, LINGO) that appeared in the injured spinal cord parenchyma also contribute to inhibit the regeneration of central axons. In summary, disruption of spinal cord pathways, persistent pro-inflammatory environment, necrosis and apoptosis of neurons, glia and endothelial cells, and inhibitory environment to axonal regeneration are the main changes observed in injured spinal cord (Silva et al., 2014