Molecular Mechanisms in the Vascular and Nervous Systems following Traumatic Spinal Cord Injury

Traumatic spinal cord injury (SCI) leads to physical and psychological issues through complex pathological processes. SCI involves primary mechanical damage and secondary injury which includes vascular disruption, inflammation and glial scar formation. These events prevent nerve regeneration. Neurotrophic and growth factors, and cytokines are involved in the nervous system, and the blood-spinal cord barrier (BSCB) is damaged allowing immune cells to infiltrate. After a spinal cord injury, the microenvironment changes with various blood vessels and neurons. During the acute phase, microvasculature destruction results in cell degeneration/necrosis, and inflammatory cells release many cytokines into the injury site, which then causes ionic imbalance, excitotoxicity, calcium influx and free-radical production. The subacute phase involves astrocytes, microglia and NG2 cells stimulated by cytokines to proliferate and migrate to the lesion. Blood vessels that have ruptured or are dysfunctional (i.e., leaking) have major roles in the progressive nature of tissue loss and the inability of nerve tissue to heal in the spinal cord. Ruptured blood vessels cause hemorrhages, which accelerate tissue loss. Though angiogenesis occurs at the injury site, it doesn’t provide enough vascularization, inhibiting the body’s natural healing process.

• 1
  Neurotrophic factors like NGF, BDNF, and NT-3 are involved in the nervous system's development and maintenance, helping to rebalance the microenvironment after SCI. Mature NGF is neuroprotective, promoting neuronal differentiation and survival. BDNF has neuroprotective and growth-promoting effects, promoting regeneration and formation of damaged axons.
• 2
  Growth factors (FGF, GDNF, IGF-1, PDGF) change expression levels after SCI, affecting the spinal cord microenvironment and motor function recovery. bFGF promotes lesion formation but also improves the spinal cord microenvironment and motor function. GDNF prevents spinal cord motor neuron death and atrophy, improving locomotor function. IGF-1 enhances axonal growth of corticospinal motor neurons.
• 3
  Cytokines (IFN, ILs, TNF, chemokines) are key regulatory proteins in the immuno-inflammatory cascade and cellular repair system. IFNs, particularly IFN-β and IFN-γ, improve lower extremity locomotor function after injury. ILs, with TNF, trigger the inflammatory response. Chemokines, like CCL2, can be protective, while others, like CCL20, have opposite effects.