Microglia in multiple sclerosis - pathogenesis and imaging
1University of Turku, Turku, Finland.
Purpose Of Review:
Microglia normally protects the central nervous system (CNS) against insults. However, their persistent activation in multiple sclerosis (MS) contributes to injury. Here, we review microglia activation in MS and their detection using positron emission tomography (PET).
Recent Findings:
During lesion evolution and the progression of MS, microglia activity may contribute to neurotoxicity through the release of pro-inflammatory cytokines, reactive oxidative species, proteases and glutamate. A means to detect and monitor microglia activation in individuals living with MS is provided by positron emission tomography (PET) imaging using the mitochondrial 18-kDa translocator protein (TSPO) ligand. TSPO PET imaging shows increased microglial activation within the normal appearing white matter that precedes radiological signs of neurodegeneration measured by T2 lesion enlargement. PET-detected microglia activation increases with progression of MS. These findings demand the use of CNS penetrant inhibitors that affect microglia. Such therapies may include hydroxychloroquine that is recently reported in a small study to reduce the expected progression in primary progressive MS, and Bruton's tyrosine kinase inhibitors for which there are now eleven Phase 3 registered trials in MS.
Summary:
Microglial activation drives injury in MS. PET imaging with microglia-specific ligands offer new insights into progression of MS and as a monitor for treatment responses.
Insights
Persistent microglia activation drives injury in multiple sclerosis (MS). Positron emission tomography (PET) imaging detects this activation, offering insights into MS progression and treatment monitoring.
Area of Science:
- Neuroscience
- Immunology
- Radiology
Background:
- Microglia are central nervous system immune cells crucial for protection.
- Persistent microglia activation contributes to neurodegeneration in multiple sclerosis (MS).
Purpose of the Study:
- To review microglia activation in MS.
- To discuss the use of positron emission tomography (PET) for detecting microglia activation in MS.
Main Methods:
- Review of existing literature on microglia activation in MS.
- Discussion of PET imaging using the mitochondrial 18-kDa translocator protein (TSPO) ligand for detecting microglia.
Main Results:
- Microglia activation contributes to neurotoxicity in MS through various mediators.
- TSPO PET imaging reveals increased microglia activation in normal-appearing white matter preceding radiological signs of neurodegeneration.
- PET-detected microglia activation correlates with MS progression.
Conclusions:
- Microglial activation is a key driver of injury in MS.
- PET imaging with microglia-specific ligands provides valuable insights into MS progression.
- PET imaging can serve as a tool for monitoring treatment responses in MS.
