The dynamics of oligodendrocyte populations following permanent ischemia promotes long-term spontaneous remyelination of damaged area

Stroke is a major public health concern, whit limited clinically approved interventions available to enhance sensorimotor recovery beyond reperfusion. Remarkably, spontaneous recovery is observed in certain stroke patients, suggesting the existence of a self-brain repair mechanism not yet fully understood. In a rat model of permanent cerebral ischemia, we described an increase in oligodendrocytes expressing 3RTau in damaged area. Considering that restoration of myelin integrity ameliorates symptoms in many neurodegenerative diseases, here we hypothesize that this cellular response could trigger remyelination. Our results revealed after ischemia an early recruitment of OPCs to damaged area, followed by their differentiation into 3RTau+ pre-myelinating cells and subsequent into remyelinating oligodendrocytes. Using rat brain slices and mouse primary culture we confirmed the presence of 3RTau in pre-myelinating oligodendrocytes and a subset of mature. The myelin status analysis confirmed long-term remyelination in the damaged area. Postmortem samples from stroke subjects showed a reduction in oligodendrocytes, 3RTau+ cells, and myelin complexity in subcortical white matter. In conclusion, the dynamics of oligodendrocytes populations after ischemia reveals a spontaneous brain self-repair mechanism which restores the functionality of neuronal circuits long-term by remyelination of damage area. This is evidenced by the improvement of sensorimotor functions in ischemic rats. A deep understanding of this mechanism could be valuable in the search for alternative oligodendrocyte-based, therapeutic interventions to reduce the effects of stroke. ### Competing Interest Statement The authors have declared no competing interest. The data are available from the corresponding author upon reasonable request. * BCAS1 : Brain enriched Myelin Associated Protein 1 IDI : Ischemic Damage Index MAG : myelin-associated glycoprotein MBD : Microtubule-Binding Domain MBP : myelin basic protein MOG : myelin oligodendrocyte glycoprotein NG2 : nerve/glial-antigen 2 OLGs : oligodendrocytes OPCs : oligodendrocyte precursor cells PDGFRα : Platelet-Derived Growth Factor Receptor Type α PFA : paraformaldehyde PLP : proteolipid protein pMCAo : permanent middle cerebral artery occlusion).