remyelination

Microglia regulate remyelination via inflammatory phenotypic polarization in CNS demyelinating disorders

The role of CNS microglia in health and disease

Microglia are the resident CNS macrophages of the brain parenchyma. They have many and opposing roles in health and disease, ranging from inflammatory to anti-inflammatory and protective functions, depending on the developmental stage and the disease context. In Multiple Sclerosis, microglia are involved to important hallmarks of the disease, such as inflammation, demyelination, axonal damage and remyelination, however the exact mechanisms controlling their transformation towards a protective or devastating phenotype during the disease progression remains largely unknown until now. We wish to understand how brain microglia respond to demyelinating insults and how their behaviour changes in recovery. To do so we developed a novel histopathological analysis approach in 3D and a cell-based analysis tool that when applied in the cuprizone model of demyelination revealed region- and disease- dependent changes in microglial dynamics in the brain grey matter during demyelination and remyelination. We now use similar approaches with the aim to unravel sensitive changes in microglial dynamics during neuroinflammation in the EAE model. Furthermore, we employ constitutive knockout and tamoxifen-inducible gene-targeting approaches, immunological techniques, genetics and bioinformatics and currently seek to clarify the specific role of the brain resident microglial NF-κB molecular pathway versus other tissue macrophages in EAE.

Valentine’s Day for people with multiple sclerosis: promoting brain repair through remyelination

Current disease-modifying therapies in multiple sclerosis are all focused on suppressing the inflammatory phase of the disease. This has been extremely successful, and it is doubtful that significantly more efficacious anti-inflammatory treatments will be found. However, it remains the case that people with relapsing-remitting multiple sclerosis acquire disability on treatment, and enter the secondary progressive phase. I argue that we now need treatments that prevent neuronal degeneration. The most promising approach is to prevent axons degenerating by remyelination. Since the discovery that the adult brain contains stem cells which can remyelinate, the problem now is how to promote endogenous remyelination, and how to know when we have achieved this! We have successfully identified one drug which promotes remyelination but unfortunately it is too toxic for use in the clinic. So the hunt continues.

Pro-regenerative functions of microglia in demyelinating diseases

Our goal is to understand why myelin repair fails in multiple sclerosis and to develop regenerative medicines for the nervous system. A central obstacle for progress in this area has been the complex biology underlying the response to CNS injury. Acute CNS damage is followed by a multicellular response that encompasses different cell types and spans different scales. Currently, we do not understand which factors determines lesion recovery. Failure of inflammation to resolve is a key underlying reason of poor regeneration, and one focus is therefore on the biology of microglia during de- and remyelination, and their cross talk to other cells, in particular oligodendrocytes and the progenitor cells. In addition, we are exploring the link between lipid metabolism and inflammation, and its role in the regulation of regeneration. I will report about our recent progress in our understanding of how microglia promote regeneration in the CNS.

Exploring the Mechanism of Action of the Novel Remyelination Therapy Nefiracetam

Failed remyelination of the non-human primate optic nerve leads to axon degeneration, retinal damages and visual dysfunction

Immunocompetent cerebral spheroids as a model system to evaluate drug-mediated demyelination and to study remyelination

IRF5 is essential for proper myelin degradation and remyelination

Remyelination of damaged axons after ischemic stroke using a stem-cell-based approach

Elucidating the impact of demyelination and remyelination on inhibitory synaptic transmission in the somatosensory cortex of a mouse model of cuprizone

FENS Forum 2024

The inhibition of oligodendrocyte remyelination after spinal cord injury results in cognitive impairment and delayed/inhibited locomotor recovery in aged mice

FENS Forum 2024

Interleukin-33 as a player in axon remyelination in response to CNS and PNS injury

FENS Forum 2024

Longitudinal single-cell and brain transcriptomic characterization of microglia signatures during experimental demyelination and remyelination

FENS Forum 2024

Role of NCOR1 and NCOR2 transcriptional corepressors in myelin development and remyelination

FENS Forum 2024

Tissue plasminogen activator (tPA) contributes to peripheral remyelination after sciatic nerve injury

FENS Forum 2024