Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury

Abstract

Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury. These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins. In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI. The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion. The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury. These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue.

How and why do T cells and their derived cytokines affect the injured and healthy brain?

“…Several mechanisms of T cell-derived harm (parts a–c ) and benefit (parts d–f ) have been proposed. a | T cells that acquire either the type 1 T helper (T H 1) or T H 17 phenotypes after CNS injury can secrete cytokines such as interleukin-17 (IL-17), IL-23 and interferon-γ(IFNγ), which have detrimental actions 126 . b | In certain circumstances, T cells can acquire detrimental auto-immune activity, skewing to a T H 1 phenotype and resulting in increased tissue injury.…”

PEG-<em>b</em>-(PELG-<em>g</em>-PLL) nanoparticles as TNF-&alpha; nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications

“…23,33,37,38 TNF-α acts as an effector molecule in brain development and is often involved in different signaling pathways to elicit the activation of macrophages and glial cells for neurotoxin production and to initiate the apoptosis/ death process in neurons. [39][40][41] Until now, the overall role of α α α α α α α α α α α α Figure 5 The levels of sOD, MDa, Il-4, Il-6, Il-8, Il-10, and NO in the rat brain tissue (n=10). Notes: (A) sOD; (B) MDa; (C) Il-4; (D) Il-6; (E) Il-8 and Il-10; (F) NO.…”

Biomaterials for Local, Controlled Drug Delivery to the Injured Spinal Cord

“…Growth factor release immediately after injury can help protect neurons from secondary injury (Garcia et al, 2016). However, the scaffolds must also enable long-term delivery of growth factor to regenerate axons during the chronic phase of injury.…”