New study uncovers role of microglia in multiple sclerosis lesions

Recent research has shed light on the initial stages of lesion development in multiple sclerosis (MS), revealing the involvement of small clusters of immune cells known as microglia. Scientists are delving into the mechanisms by which these microglial clusters may progress into MS lesions, aiming to identify new therapeutic targets for combating the disease.

In MS, inflammation within the brain and spinal cord results in areas of damaged nerve tissue, characterised by lesions. However, the precise process underlying lesion formation remains incompletely understood.

Microglia, the resident immune cells of the brain, play crucial roles in brain defence and maintenance by combating infections and clearing molecular debris. Notably, in MS patients, microglia sometimes aggregate into abnormal clusters called microglia nodules. While these nodules have been observed for decades, their significance in lesion development has been unclear.

Previous theories proposing microglia nodules as early indicators of lesion formation faced scepticism due to their presence in other neurological disorders like stroke, which lack lesion formation. Thus, understanding the distinctions between microglia nodules in MS and those in other conditions is crucial.

To investigate further, scientists analysed brain samples from MS patients and individuals who had had a stroke. They found that MS patients with microglia nodules exhibited more lesions and signs of active inflammation compared to those without nodules.

Comparative analysis revealed differences between microglia nodules in MS and stroke cases. Microglia nodules in MS showed increased expression of inflammatory genes associated with MS lesions, as well as a more inflamed microenvironment. Moreover, a significant proportion of microglia nodules in MS brains were located near nerve fibres with damaged myelin, the fatty sheath surrounding nerve fibres.

The study suggests that activated microglia, triggered by the breakdown of myelin and inflammatory signals from other immune cells, contribute to tissue damage, potentially initiating lesion formation in MS.

These findings indicate that some microglia nodules may serve as sites for lesion initiation in MS, presenting a promising target for therapeutic interventions aimed at preventing early demyelination and lesion formation.

The study underscores the importance of understanding microglia’s role in MS pathology and highlights potential avenues for developing targeted treatments to mitigate disease progression.