Axons? More like Axoffs
Demyelinated axons redistribute these channels along previously myelinated membrane in an attempt to restore action-potential conduction.
What are voltage-gated sodium channels?
This adhesion molecule on activated leukocytes binds VCAM-1 on CNS endothelium and facilitates migration across the blood-brain barrier. It is also the target of a medical therapy for MS.
What is VLA-4 (α4β1 integrin)?
This lipid-rich structure surrounding CNS axons is the most obvious target of inflammatory injury in MS.
What is myelin?
Excessive extracellular concentrations of this excitatory neurotransmitter can injure neurons and oligodendrocytes through excitotoxicity.
What is glutamate?
This MS medication blocks α4-integrin and therefore prevents leukocyte trafficking into the CNS.
What is natalizumab?
Loss of these CNS cells causes failure to maintain and regenerate myelin.
What are oligodendrocytes?
Activated microglia and macrophages generate these chemically reactive molecules, which can damage proteins, lipids, DNA, and mitochondria.
What are reactive oxygen and nitrogen species?
Leukocytes initially slow and interact with vascular endothelium through this general process before firm adhesion and transmigration.
What is leukocyte rolling?
Permanent neurological disability in MS correlates more closely with damage to these structures than with demyelination alone.
What are axons?
Mitochondrial dysfunction causes insufficient ATP generation, ultimately impairing Na⁺/K⁺ ATPase activity and producing this metabolic state in chronically demyelinated axons.
What is energy failure?
These soluble signaling molecules establish gradients that guide activated leukocytes toward sites of CNS inflammation.
What are chemokines?
In addition to white matter, MS pathology frequently affects this CNS tissue rich in neuronal cell bodies
What is gray matter?
Increased intracellular sodium can reverse this exchanger, producing accumulation of a second ion that activates proteases and contributes to axonal degeneration.
What is the Na⁺/Ca²⁺ exchanger, causing Ca²⁺ accumulation?
These enzymes released by inflammatory cells can degrade extracellular matrix and basement membrane components, facilitating penetration of the blood-brain barrier.
What are matrix metalloproteinases (MMPs)?
This innate lymphocyte population can modulate MS inflammation by killing activated autoreactive T cells and producing cytokines, with the CD56^bright subset often associated with immunoregulatory effects.
What are natural killer (NK) cells?