Neuroglia are essential for the support and protection of neurons.

How BBB breakdown initiates initial glial involvement?

The BBB is the main structure altered in neuroinflammation, losing its permeability as a result of astrocyte activation, excessive production of cytokines and chemokines, and immune cell infiltration. Astrocytes are part of the neurovascular unit — their endfeet wrap around endothelial cells, and they secrete mediators that promote the BBB phenotype, so when they become activated in inflammation, barrier properties are compromised. Microglia act as the CNS's immune cells and are key players in generating the inflammatory response during inflammation, expressing inflammatory cytokines (e.g. IL-1, TNF), chemokines, prostaglandins and reactive oxygen species once activated.

What are astrocytes?

Neuroglia found in the CNS. They maintain the blood-brain barrier (BBB), create a 3D framework for the CNS, repair damaged nervous tissue, guide neuron development, and control the interstitial environment.

What is the role of astrocytes in maintaining CNS homeostasis?

(1) Maintain the BBB — their feet form a blanket around capillaries and secrete chemicals that maintain the BBB's selective permeability. (2) 3D framework — their extensive cytoskeleton provides a structural framework for neurons. (3) Repair — they move to injury sites to stabilize tissue and prevent further injury. (4) Guide development — in embryonic brain development they direct growth and formation of neuron connections. (5) Control the interstitial environment — regulate concentrations of Na⁺, K⁺ and CO₂; provide a rapid-transit system for nutrients, ions and dissolved gases between neurons and capillaries; control blood flow volume through capillaries; absorb and recycle some neurotransmitters; and release chemicals that modulate communication across axon terminals.

What are oligodendrocytes?

Neuroglia found in the CNS. They are responsible for creating the myelin sheath around neuronal axons; multiple oligodendrocytes work together to myelinate one axon, and each one myelinates multiple axons.

What is the role of oligodendrocytes in maintaining CNS homeostasis?

They create the myelin sheath around the axons of CNS neurons, providing the insulation needed for normal saltatory signalling.

What are microglia?

Neuroglia found in the CNS that work as immune cells, engulfing debris, waste and pathogens.

What is the role of microglia in maintaining CNS homeostasis?

They act as immune cells by engulfing debris, waste and pathogens — keeping the CNS clear of cellular waste and threats.

What does multiple sclerosis (MS) do to the CNS?

Immune cells attack and destroy the myelin sheaths encasing neuronal axons and potentially the oligodendrocytes that produce them; the blood-brain barrier relaxes, allowing peripheral immune cells (normally not granted access to the CNS) to enter. This disrupts saltatory signalling and leads to demyelination with conduction failure, and over time astrocyte reactivity, glial scarring, and axonal loss/neurodegeneration.

How do astrocytes respond to the environment of MS in the CNS?

Over time they become reactive: they proliferate, secrete inflammatory mediators, and eventually form glial scars, which inhibit remyelination and axonal regeneration and permanently disrupt connectivity.

How do oligodendrocytes respond to the environment of MS in the CNS?

They can be attacked and destroyed by the immune system along with the myelin sheaths they produce. Their loss removes support from axons, and remyelination is further prevented by glial scarring.

How do microglia respond to the environment of MS in the CNS?

They become activated and amplify the inflammatory response.

How does MS break down the blood-brain barrier (BBB)?

The immune-mediated attack on myelin causes an increase in inflammation; this increased inflammation raises the permeability of the BBB, allowing peripheral immune cells to enter the CNS.

What does demyelination do to signalling?

Damage to CNS myelin sheaths leads to loss of saltatory conduction, decreased conduction speed, and conduction block (where an action potential doesn't propagate at all). In early stages conduction may be restored by redistribution of ion channels along the demyelinated axon, but this is inefficient and energetically taxing.

What are the long-term consequences of glial scarring on axonal regeneration and CNS connectivity?

Glial scars inhibit remyelination and axonal regeneration, permanently disrupting connectivity. Combined with the CNS's very limited regenerative capability, this makes the damage effectively irreversibl