Secondary Spinal Cord Injury llI: Pathophysiology

Within minutes of the primary phase of a spinal cord injury, a secondary injury phase of damage begins and can last for weeks.

Vascular disruption and ischemia impair mitochondrial function, leading to ATP depletion and failure of ATP-dependent ion pumps. This leads to intracellular water accumulation and progressive tissue injury.

Damaged neurons release excess glutamate, overstimulating NMDA receptors and allowing calcium to surge into cells, worsening mitochondrial injury.

At the same time, microglia activate, and immune cells infiltrate from the bloodstream.

Their cytokines, chemokines, and reactive oxygen species increase blood–spinal cord barrier permeability, producing vasogenic edema, raising pressure, and further reducing perfusion.

Continued low oxygen and inflammation cause oxidative stress, and many cells undergo delayed programmed cell death.

Oligodendrocytes are especially vulnerable; their loss strips axons of myelin, slowing conduction and contributing to lasting deficits. In later stages, reactive astrocytes form a glial scar that limits the injury.