Spinal Cord Injury MDR

Dorsal Compartment of the Vertebrae

Includes the articular processes, laminae, pedicles and spinous processes

The Middle Compartment of the Vertebrae

Contains the dorsal longitudinal ligament, the dorsal aspect of the vertebral body, and the dorsal portion of the annulus fibrosis

Ventral Compartment of the Vertebrae

Contains the ventral longitudinal ligament, the lateral and ventral aspects of the annulus fibrosis, the nucleus pulposus, and the remaining portions of the vertebral body

Three Compartment Model of the Vertebrae

Dorsal, middle, and ventral compartments

Damage to any two of the three compartments results in spinal instability

Primary Spinal Cord Injury

Damage to the vertebrae, spinal cord, and supporting structures that occur as a direct result of the trauma

Secondary Spinal Cord Injury

Consists of a large number of biochemical processes that occur as a result of the primary injury and that perpetuates spinal cord damage in the hours to days after the primary injury occurs

Pathophysiology of Secondary Spinal Cord Injury

Damage to neuronal membranes, release of excitatory neurotransmitters such as glutamate and activation of voltage-gated calcium channels lead to an influx of calcium into the neuron, leading to apoptosis

Extracellular concentrations of excitatory neurotransmitters such as glutamate and aspartate are increased after trauma due to release by damaged neurons as well as decreased clearance by ischemic astrocytes

• Excitatory neurotransmitters activate a number of neuronal receptors, causing influx of sodium and calcium, as well as causing cellular swelling

Sequence of Events that Begins with Vascular Compromise and Local Hemorrhage as a Result of the Spinal Cord Trauma

Damaged endothelial cells lead to extravasation of RBCs into the spinal cord parenchyma and express increased intercellular adhesion molecules on their surfaces, which bind to integrins on the surface of white blood cells, leading to influxes of leukocytes into damaged spinal cord tissue

Hemolysis of the extravasated RBCs provides ferrous iron (Fe2+) as a substrate to the Fenton reaction, leading to the production of large amounts of hydroxyl radicals

Nitric oxide (NO) synthase induction leads to increased NO concentrations and subsequent production of peroxynitrite

Free radicals induce cellular and tissue injury, including lipid peroxidation, DNA damage, and protein degradation

Role of Glial Cells in Secondary Injury

TLRs on microglial cells bind to ligands indicative of cellular injury, triggering activation of the cells into one of two amoeboid phenotypes, pro-inflammatory M1 (classical activated) microglial cells and anti-inflammatory M2 (alternatively activated) microglial cells

• M1 cells promote apoptosis and necrosis through multiple signaling pathways including inflammatory cytokines, chemokines, iNOS, production of reactive oxygen species, the excitatory neurotransmitter glutamate, and proteases

• M2 cells lead to the production of anti-inflammatory mediators and ultimately lead to cell survival and axonal regeneration

Astrocytes differentiate into similar pro-inflammatory M1 and anti-inflammatory M2 phenotypes

Spinal Shock

The transient development of lower motor neuron signs caudal to the level of an acute spinal cord injury

• Likely due to the loss of descending excitatory input to lower motor neurons, resulting in hyperpolarization of these neurons

• In time the LMNs become excitable again

What is the most important protective effect of methylprednisolone sodium succinate in patients with spinal cord injury?

Free-radical scavenging property

Dexamethasone and prednisone do not have this property and are unlikely to have any significant neuroprotective effect