Remyelination

[Petr75]

2022 Mar 4
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA
Breaking the barriers to remyelination in multiple sclerosis
https://pubmed.ncbi.nlm.nih.gov/35255453/


Abstract

Chronically demyelinated axons are rendered susceptible to degeneration through loss of trophic support from oligodendrocytes and myelin, and this process underlies disability progression in multiple sclerosis. Promoting remyelination is a promising neuroprotective therapeutic strategy, but to date, has not been achieved through simply promoting oligodendrocyte precursor cell differentiation, and it is clear that a detailed understanding of the molecular mechanisms underlying failed remyelination is required to guide future therapeutic approaches. In multiple sclerosis, remyelination is impaired by extrinsic inhibitory cues in the lesion microenvironment including secreted effector molecules released from compartmentalized immune cells and reactive glia, as well as by intrinsic defects in oligodendrocyte lineage cells, most notably increased metabolic demands causing oxidative stress and accelerated cellular senescence. Promising advances in our understanding of the cellular and molecular mechanisms underlying these processes offers hope for strategically designed interventions to facilitate remyelination thereby resulting in robust clinical benefits.

[Petr75]

2024 May 12
Paired vagus nerve stimulation drives precise remyelination and motor recovery after myelin loss
https://pubmed.ncbi.nlm.nih.gov/38766201/


Abstract

Myelin loss in the central nervous system can cause permanent motor or cognitive deficits in patients with multiple sclerosis (MS). While current immunotherapy treatments decrease the frequency of demyelinating episodes, they do not promote myelin repair or functional recovery. Vagus nerve stimulation (VNS) is a neuromodulation therapy which enhances neuroplasticity and the recovery of motor function after stroke, but its effects on myelin repair are not known. To determine if VNS influences myelin repair, we applied VNS following a demyelinating injury and measured longitudinal myelin dynamics and functional recovery. We found that VNS promotes remyelination by increasing the generation of myelinating oligodendrocytes. Pairing VNS with a skilled reach task leads to the regeneration of myelin sheaths on previously myelinated axon segments, enhancing the restoration of the original pattern of myelination. Moreover, the magnitude of sheath pattern restoration correlates with long-term motor functional improvement. Together, these results suggest that recovery of the myelin sheath pattern is a key factor in the restoration of motor function following myelin loss and identify paired VNS as a potential remyelination therapy to treat demyelinating diseases.

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https://www.mayoclinic.org/tests-proced ... c-20384565