3.15

Secondary Spinal Cord Injury llI: Pathophysiology

383 views01:25 min

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.

Overview

Loading...

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

Early Ischemia and Ionic Imbalance

Within minutes of spinal cord injury, a secondary cascade begins, progressing over hours to weeks. Vascular damage reduces blood flow, causing ischemia and mitochondrial dysfunction. ATP depletion leads to ion pump failure, membrane depolarization, sodium influx, potassium efflux, and water accumulation, resulting in cellular swelling. Increased intracellular calcium further disrupts mitochondria and accelerates cellular injury.

Excitotoxicity and Neuronal Damage

Damaged neurons release excess glutamate, overstimulating NMDA receptors and allowing more calcium influx. Elevated calcium activates destructive enzymes, worsens mitochondrial dysfunction, and promotes progressive neuronal damage.

Inflammation, Edema, and Secondary Cellular Damage

Microglia activate rapidly, and immune cells infiltrate through damaged vessels. These cells release cytokines, chemokines, and reactive oxygen species, intensifying inflammation and tissue injury.

Inflammation increases permeability of the blood–spinal cord barrier, leading to vasogenic edema and extracellular fluid accumulation. Rising tissue pressure further reduces perfusion, worsening ischemia and creating a self-amplifying cycle of injury.

Sustained hypoxia and inflammation generate oxidative stress, damaging lipids, proteins, and DNA, and triggering delayed programmed cell death in neurons and glial cells, expanding the lesion.

Demyelination and Glial Scar Formation

Oligodendrocytes are particularly vulnerable to secondary injury. Their loss results in demyelination of axons, slowing nerve conduction, and contributing to persistent functional deficits. In later stages, reactive astrocytes proliferate and form a glial scar, which helps contain the injury but also inhibits axonal regeneration.

Clinical Manifestations

These secondary injury mechanisms progressively enlarge the area of damage beyond the original insult. As a result, patients may experience worsening neurological deficits over time, including loss of motor and sensory function, reflecting the expanding lesion and impaired neural conduction.

Transcript

Explore More Videos

Spinal Cord Injury

Secondary Injury

Ionic Imbalance

Oxidative Stress

Neuronal Damage