Multiple Sclerosis (MS) is an autoimmune disease leading to demyelination and axonal loss in the brain and spinal cord. The hallmarks of the pathology are plaques found in the myelin-rich white matter region of the central nervous system.
Immune mechanisms and pro-inflammatory molecules released lead to the destruction of myelin sheaths and cells producing them, the oligodendrocytes. Neuroaxonal loss is a result of Wallerian and retrograde degeneration induced by axonal transaction in focally demyelinated lesions. Mechanistically, reactive oxygen species and nitric oxide play a key role in inducing early, acute axonal damage. Mitochondrial dysfunction and enhancement of the glutamatergic transmission are also consequences of chronic exposure to pro-inflammatory cytokines.
However, mechanisms leading to axonal damage are not fully understood. Recent advances hypothesize about an autonomous degenerative component in MS that may explain the ineffectiveness of immunosuppressive or immunomodulatory therapies on patients with progressive MS and support the development of their combination with neuroprotective approaches.
- Primary culture of oligodendrocytes precursors
- Cortical neurons
- Myelinating coculture of oligodendrocytes and central neurons (Picture 1 and 2)
Models of intoxication:
- Glutamate injuries
- TNF α injuries
- Pharmacological demyelination
- Oligodendrocyte morphology / survival
- Differentiation and maturation of oligodendrocyte precursors
- Loss of neurites
- Myelination of central neurons by OPC (kinetic of myelination)
- Marker of myelination expression
Kinetic curve of oligodendrocyte precursors (OPC) proliferation, maturation and differentiation.