Myelin Repair: From Animal Models to Humans

Abstract

It is widely thought that brain repair does not occur, but myelin regeneration provides clear evidence to the contrary. Spontaneous remyelination may occur after injury or in multiple sclerosis (MS). However, the efficiency of remyelination varies considerably between MS patients and between the lesions of each patient. Myelin repair is essential for optimal functional recovery, so a profound understanding of the cells and mechanisms involved in this process is required for the development of new therapeutic strategies. In this review, we describe how animal models and modern cell tracing and imaging methods have helped to identify the cell types involved in myelin regeneration. In addition to the oligodendrocyte progenitor cells identified in the 1990s as the principal source of remyelinating cells in the central nervous system (CNS), other cell populations, including subventricular zone-derived neural progenitors, Schwann cells, and even spared mature oligodendrocytes, have more recently emerged as potential contributors to CNS remyelination. We will also highlight the conditions known to limit endogenous repair, such as aging, chronic inflammation, and the production of extracellular matrix proteins, and the role of astrocytes and microglia in these processes. Finally, we will present the discrepancies between observations in humans and in rodents, discussing the relationship of findings in experimental models to myelin repair in humans. These considerations are particularly important from a therapeutic standpoint.

The Use of Iron Oxide Nanoparticles to Reprogram Macrophage Responses and the Immunological Tumor Microenvironment

“…IONPs have also been used to track microglia and assayed as a potential nanocarrier in brain tumors. Microglia are highly phagocytic cells found entirely in the central nervous system (CNS) where they protect the nervous tissue from debris and damaged CNS structures and from viruses, microorganisms, and tumors (123)(124)(125)(126). Therefore, like macrophages, microglia can phagocytose IONPs and react to them.…”

Brain Plasticity in Humans and Model Systems: Advances, Challenges, and Future Directions

“…The division of oligodendrocyte progenitor cells plays a role in myelination, which is a widespread phenomenon across the CNS and is more common than neuron production during postnatal development [79]. Additionally, these plastic processes show remarkable interspecies differences, which make it difficult to reconcile data obtained in mice and humans [6,110]. Hence, we have limits to our capability to define (and measure) the degrees of CNS tissue immaturity due to an intermix of different cellular and molecular features leading to plastic changes, which can vary among individuals as a consequence of their life experiences.…”

“…Many strategies used to alleviate disease or brain damage rely on plastic features of the nervous system. Stem cells have much potential for brain repair [1,2]; nevertheless, their occurrence and endogenous regenerative capacity have limits in mammals [3][4][5][6][7]. The nervous systems of some non-mammalian vertebrates (e.g., reptiles, axolotls, fish) have striking potential for regeneration [8][9][10] relative to mammals [3,4,7].…”

Oligodendrocyte Development and Implication in Perinatal White Matter Injury

“…Thus, therapeutic enhancement of endogenous oligodendrogenesis and myelination is another promising WMI therapeutic strategy. This can be achieved by either testing known regulators of OL development or high throughput screening ( Cayre et al, 2021 ; Table 3 ).…”