Intervertebral Disc Disease Anatomy and Pathophysiology

The vertebral column supports the neck and back and is composed of bony vertebral bodies connected by cushioning intervertebral discs. The vertebral canal is the hollow space formed by the vertebral bodies occupied by the spinal cord. The spinal cord is the nerve bundle responsible for all nerve impulses to and from the body.
The normal intervertebral disc (IVD) cushion is shaped like a jelly donut. The interior “jelly” is made of a rich extracellular matrix that forms the central gelatinous nucleus pulposus, which contains cartilage-like cells. This “jelly” is contained by the rest of the “donut” or annulus fibrosus, made of tougher fibroblast-like cells. This cushioning jelly donut structure is connected to the adjacent bone of the vertebral bodies by cartilaginous endplates.

The “jelly” consists of collagen and proteoglycans which are large molecules capable of attracting and retaining water. Functionally, the collagen provides shape and tensile strength, while proteoglycans confer tissue viscoelasticity, stiffness, and resistance to compression, through their interaction with water. A proper balance between matrix synthesis and degradation is responsible for the maintenance of the integrity of the IVD and hence the mechanical behavior of the IVD itself. This is related to the activity of cellular signaling molecules such as cytokines, growth factors, enzymes, and enzyme inhibitors that act to modulate the action of the cells (and stem cells) that make the collagen and proteoglycans. Degeneration of the structure of the annulus fibrosus and the nucleus pulposus occur early in life in chondrodystrophic breeds resulting in shape and molecular changes in the IVD. Progressive degeneration results in loss of water from the “jelly” in the disc and eventual expulsion of the dehydrated “jelly” from the disc resulting in compression of the spinal nerves and spinal cord itself. Intervertebral Disc Disease (IVDD) occurs when the cartilage disc deforms or ruptures causing pressure and or damage to the spinal cord.

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Figure 1. Normal Anatomy of Intervertebral Disc and Spinal Canal.

As the intervertebral disc degenerates we see dehydration and tears of the disc annulus and nucleus pulposus. At a molecular level, we see decreased cell viability and proteoglycan synthesis and reduced diffusion of nutrient and waste products. This leads to accumulation of dead cellular debris, degraded matrix macromolecules, and an increased degrading enzymatic activity along with a modification of the collagen distribution. It is at this level that stem cells function to regenerate healthy matrix and reform the normal shape of the IVD.

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Figure 2. Intervertebral Disc Disease: Spinal nerve root and spinal cord compression caused by extruded nucleus pulposus.
The disc space is narrower, causing folding and dorsal impingement of the spinal cord by the dorsal longitudinal ligament.

Spinal cord damage from IVDD results from outward to inward compression of the spinal cord. The spinal cord neurons are organized with the less important neurons on the outside and the more important ones on the inside. The outer neurons conduct proprioceptive messages that tell the location and position of the limbs to the brain. The innermost tissues of the spinal cord contain nerve tracts responsible for relaying information from the brain to the muscles. The grey matter of the spinal cord contains nerve cell bodies responsible for spinal reflexes and for coordination. Initial damage to the spinal nerves results in pain as a primary sign, as compression becomes more severe, loss of proprioception is evident, followed by loss of coordination, followed by loss of motor control, then finally loss of deep pain perception. Localization of damage to one side of the spinal cord is evident by comparing the degree of damage and loss of nerve function on one side versus the other.

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Figure 3. Spinal Nerve Tracts: Nerve bundles to and from the brain are organized into tracts. These tracts are compressed during IVDD resulting in loss of their function. Depending on the location and severity of the compression, different functions are lost allowing prognostic decisions to be made.

Central nervous system regeneration is highly limited after injury. Spinal cord injury (SCI) leads to cell death, particularly in neurons, oligodendrocytes, astrocytes, and precursor cells. Any cavities and cysts resulting from this cell death and loss may interrupt healing of axonal tracts. SCI culminates in glial scarring, a multifactorial process involving reactive astrocytes, glial progenitors, microglia, macrophages, fibroblasts, and Schwann cells. Such scars are often oriented across the neuron path and contain transmembrane molecular inhibitors of axon growth, and appear impenetrable. Lack of regenerative capacities of adult spinal cords results from neuron growth inhibitors of myelin proteins, glial scar formation and a poorly defined extracellular matrix-derived factor. Stem cells regenerate the spinal cord by differentiating into astrocytes and oligodendrocytes, as well as neuronal cells. Neurons derived from engrafted stem cells may relay signals from disrupted fibers in the host, including local circuit interneurons or ascending fibers that are present in the dorsal column and grey matter. This neuronal transdifferentiation (changing from one cell type to another based on chemical and molecular by-products) process that occurs with adipose derived stem cells results from the interactions of cells, cytokines provided by these cells, growth factors, and intercellular signals. Adipose derived stem cells have been shown to secrete multiple angiogenic (blood vessel growth) and anti-apoptotic (anti cell death) cytokines that support tissue regeneration and minimize tissue damage. Engrafted stem cells and the chemical factors released by the spinal cord injury play important roles in the proliferation, migration and differentiation of existing spinal cord stem cells. The adipose derived stem cells that survive produce large amounts of fibroblast growth factor and vascular endothelial growth factor in the host spinal cord. These cytokines have been shown to promote neurogenesis.