Immunoactivation and Altered Intercellular Communication Mediate the Pathophysiology of Spinal Cord Injury

Abstract

Evidence and inferences from clinical research, clinical observation, and literature review support an etiologic paradigm for the pathophysiology of spinal cord injury (SCI). According to this paradigm, changes in immunoregulation and in the activation of cytokines or intercellular adhesion molecules (ICAMs) contribute to many of the comorbidities, metabolic changes, and pathophysiologic sequelae observed after traumatic SCI. Cytokines and ICAMs are endogenously secreted molecules that serve as intercellular signals and immunoregulators. They modulate the activity of cells and influence the organization and function of tissues or organs. These intercellular signals are posited as molecular links between the damaged, decentralized nervous system of SCI and the acquired autonomic failure, neuroendocrine-immunoregulatory dysfunction, diminished central nervous system (CNS) regenerative capacity, and broad spectrum of pathology, organ failure, and generalized impairment of homeostasis caused by trauma to the spinal cord. These highly bioactive molecules may also mediate or facilitate the intralesional CNS axonal damage and peripheral neurologic deficits sustained at time of acute CNS injury. Ultimately, it should be possible to develop treatments that will block or modulate the local and systemic expression of cytokine or ICAM bioactivity. Such treatments might aid victims of SCI by diminishing overall morbidity or mortality, helping restore sensorimotor function and homeostasis, and enhancing longevity and quality of life.

Acute spinal cord injury: Pathophysiology and pharmacological intervention (Review)

“…Nevertheless, extensive experiments show that the spinal cord has excellent healing properties (22). Proper blood flow is an essential factor in ensuring that progressive tissue damage precedes and promotes necrosis during the healing process (23).…”

“…Peripheral immune cells, including macrophages, neutrophils and T cells, can initiate an inflammatory response following SCI, which may gradually increase within a few days (22). Macrophages and neutrophils can cause the growth of lesions and lead to tissue damage (Fig.…”

Spinal cord injury – scientific challenges for the unknown future

“…However, their pos- sible use is complicated by the difficulties in determining at what time point these molecules should be administered in order to interfere in an efficient way with the inflammatory process (45).…”