MS is a chronic disease affecting the central nervous system, including the brain, spinal cord, and optic nerves. It is characterized by inflammation and the progressive breakdown of structures supporting nerve cells, or neurons. MS is classified as a neurodegenerative disorder because it causes physical damage to nerve cells, leading to a spectrum of debilitating symptoms and permanent neurological impairment.
The Essential Role of Myelin and Oligodendrocytes
Neurons in the central nervous system rely on a specialized, fatty coating called myelin for efficient function. Myelin acts like the insulating sheath around an electrical wire, ensuring that electrical signals, or action potentials, travel quickly along the neuron’s projection, the axon.
The myelin sheath is interrupted by small gaps known as the Nodes of Ranvier. This structure allows the electrical signal to “jump” from node to node, a process called saltatory conduction, which dramatically increases signal transmission speed. The myelin-producing cells, called oligodendrocytes, also provide metabolic support to the underlying axons. They supply lactate and other substrates the axon requires for energy and function.
The Autoimmune Attack and Demyelination
The destructive process begins when the body’s immune system mistakenly targets healthy structures within the central nervous system. Immune cells, specifically T cells and B cells, become activated and breach the blood-brain barrier (BBB), a tightly regulated system that normally protects brain tissue.
Once inside, these immune cells misidentify myelin as a foreign threat, initiating inflammation. T cells release inflammatory chemicals called cytokines, recruiting other immune components, including B cells and macrophages, to the injury site. This inflammatory assault leads to the destruction of the myelin sheath, known as demyelination. The resulting areas of destruction form scar-like tissue, visible on imaging scans as lesions or plaques. The inflammation also damages oligodendrocytes, hindering immediate repair attempts.
Direct Damage to the Axon and Neuron
The loss of the protective myelin sheath exposes the underlying axon, making it vulnerable to further damage from the inflammatory environment. Although MS is initially defined by demyelination, damage to the axon itself correlates most strongly with long-term, irreversible disability. Axonal loss occurs even in the early stages of the disease and becomes more prominent in progressive forms.
A major mechanism of this direct damage involves metabolic stress and mitochondrial dysfunction. The inflammatory environment generates high levels of reactive oxygen species and nitric oxide, causing oxidative damage to the axon’s mitochondria. Since mitochondria are the energy-producing organelles, their failure leads to an energy deficit the axon cannot overcome.
The lack of myelin also disrupts the balance of ions across the axonal membrane. Without the metabolic support normally provided by the oligodendrocyte, the axon must work harder, increasing its energy demands. This chronic energy failure, coupled with inflammation, leads to the degeneration and eventual severing of the axon. This irreversible damage, known as axonal transection, is the physical basis for permanent neurological deficits and brain atrophy.
Resulting Disruption of Neural Signaling
The physical damage to neuron structures immediately impairs the nervous system’s ability to communicate. The absence of myelin insulation causes electrical signals to dissipate and leak out of the axon, preventing them from reaching their destination. Consequently, the speed of signal transmission is drastically reduced, or the signal may fail completely, a phenomenon termed conduction block.
This disruption of nerve impulse flow manifests as MS symptoms. For example, a delayed signal to a muscle group causes motor difficulties, and failure of visual signals along the optic nerve results in vision problems. Fatigue, a common complaint, is partly a consequence of the nervous system expending more energy to push slowed signals across damaged pathways. The lesion location dictates the specific functional outcome, such as weakness from motor pathway damage or bladder control issues from spinal cord damage.
The Body’s Response: Attempts at Repair
The central nervous system possesses an intrinsic, though limited, capacity for self-repair following injury. This regenerative process is driven by remyelination, an attempt to restore the damaged myelin sheath. Oligodendrocyte Progenitor Cells (OPCs), which are resident precursor cells, are recruited to the lesion site.
OPCs are meant to mature into new oligodendrocytes, which then wrap new myelin around the demyelinated axons. While this process can be effective in early MS, it often fails to keep pace with ongoing damage. When remyelination occurs, the newly formed myelin is often thinner and less effective than the original sheath, meaning signal transmission is restored but may be slower.
In chronic lesions, OPCs may be present but often fail to differentiate into mature, myelin-producing cells, a phenomenon called differentiation block. This failure, combined with axonal loss, forces the brain to rely on neuroplasticity—the ability to reroute signals through alternative, undamaged pathways. However, as axonal loss accumulates and remyelination capacity declines, these compensatory mechanisms become overwhelmed, leading to progressive and permanent disability.