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.
Cell System
- Primary culture of oligodendrocytes precursors
- Primary culture of cortical neurons
- Primary culture of Motor neuron
- Myelinating coculture of oligodendrocytes and central neurons
Image of myelinating coculture of oligodendrocyte cells (in green) and cortical neurons(in red )
Image of myelinating coculture of oligodendrocyte cells (in green) and cortical neurons(in red )
Model of Intoxication
- Glutamate injuries
- TNF α injuries
- Pharmacological demyelination
Endpoint Evalution
- Oligodendrocyte survival
- Differentiation and maturation of oligodendrocyte precursors
- Loss of neurite
- Myelination of central neurons by OPC (kinetic of myelination)
- Marker of myelination expression
- Intracellular calcium quantification
- Release of cytokines
- ...
Kinetic curve of oligodendrocyte precursors (OPC) proliferation, maturation and differentiation.