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Sunday, January 6, 2019

Mechanism of MS: A Complex Mosaic

A Closer Look at #MS Pathogenesis

The pathogenesis of multiple sclerosis (MS) involves a complex and dynamic interplay between the immune system and central nervous system (CNS) resident cells, including neurons and glial cells.1 These mechanisms contribute to the acute inflammation and diffuse neurodegeneration that characterize MS.1,2

The Role of Glial Cells

Neuroglia are a network of cells in the brain and spinal cord that support the CNS by maintaining homeostasis, producing myelin, and protecting neurons from outside attack.1,3,4
Glial cells include astrocytes, microglia, and oligodendrocytes.1
  • Astrocytes provide synaptic support, neuronal guidance, and maintain the blood-brain barrier3
  • Microglia have an important role in inflammatory and immune responses including clearing cellular debris and repairing tissues4
  • Oligodendrocytes create the myelin sheath that helps insulate axons and allows for efficient conduction of nerve impulses1

Glial Cell Activation

Glial cells are activated when immune cells, including T cells, cross the blood-brain barrier and set in motion a chain of cellular reactions.5-8
  • Cytokine Secretion: once inside the central nervous system, autoreactive T cells secrete proinflammatory cytokines1,8-10
  • Glial Activation: in response to these proinflammatory cytokines, resident glial cells such as microglia and astrocytes become activated3,8-10
  • Axonal Demyelination: activated microglia and astrocytes produce additional proinflammatory cytokines, such as TNF-α, NO, and IL-6, which play a key role in demyelination and axonal injury3,4,6,8,9
  • Oligodendrocyte Loss: inflammatory activity also results in the extensive loss and apoptosis of oligodendrocytes, which are no longer able to repair and replenish damaged myelin sheaths1,3,4

Glial Cell Activity in the Pathogenesis of MS1,3-10

Picture of Glial Cell Activity in the Pathogenesis of MS
Modified from Samuel S. Duffy, Justin G. Lees, and Gila Moalem-Taylor. The contribution of immune and glial cell types in experimental autoimmune encephalomyelitis and multiple sclerosis. Multiple Sclerosis International. Hindawi Publishing Corporation. © 2014. From an open access article distributed under the Creative Commons Attribution License, CC BY 4.0.



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