Role of Perivascular Oligodendrocyte Precursor Cells in Angiogenesis After Brain Ischemia

Abstract

Background Oligodendrocyte precursor cells ( OPC s) regulate neuronal, glial, and vascular systems in diverse ways and display phenotypic heterogeneity beyond their established role as a reservoir for mature oligodendrocytes. However, the detailed phenotypic changes of OPC s after cerebral ischemia remain largely unknown. Here, we aimed to investigate the roles of reactive OPC s in the ischemic brain. Methods and Results The behavior of OPC s was evaluated in a mouse model of ischemic stroke produced by transient middle cerebral artery occlusion in vivo. For in vitro experiments, the phenotypic change of OPC s after oxygen glucose derivation was examined using a primary rat OPC culture. Furthermore, the therapeutic potential of hypoxic OPC s was evaluated in a mouse model of middle cerebral artery occlusion in vivo. Perivascular OPC s in the cerebral cortex were increased alongside poststroke angiogenesis in a mouse model of middle cerebral artery occlusion. In vitro RNA ‐seq analysis revealed that primary cultured OPC s increased the gene expression of numerous pro‐angiogenic factors after oxygen glucose derivation. Hypoxic OPC s secreted a greater amount of pro‐angiogenic factors, such as vascular endothelial growth factor and angiopoietin‐1, compared with normoxic OPC s. Hypoxic OPC ‐derived conditioned media increased the viability and tube formation of endothelial cells. In vivo studies also demonstrated that 5 consecutive daily treatments with hypoxic OPC ‐conditioned media, beginning 2 days after middle cerebral artery occlusion, facilitated poststroke angiogenesis, alleviated infarct volume, and improved functional disabilities. Conclusions Following cerebral ischemia, the phenotype of OPC s in the cerebral cortex shifts from the parenchymal subtype to the perivascular subtype, which can promote angiogenesis. The optimal use of hypoxic OPC s secretome would provide a novel therapeutic option for stroke.

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

“…Oligodendrocyte precursor cells (OPCs) have recently emerged as one of the contributors to BBB. According to their regional differences, OPCs can be divided into two subtypes, namely, perivascular OPCs and parenchymal OPCs (Maki, 2017;Kishida et al, 2019). In the human and mouse brain, perivascular OPCs are attached to cerebral endothelial cells and pericytes through basal lamina, and thereby are thought to become novel components of the BBB (Seo et al, 2013;Maki et al, 2015).…”

Cellular Mechanisms Participating in Brain Repair of Adult Zebrafish and Mammals After Injury

“…This oligodendrogenesis has been shown to improve brain repair processes and neurological scores (Zhang et al, 2013). After brain ischemia, OPCs also seem to be involved in post-stroke angiogenesis (Kishida et al, 2019), a process linked to neurogenesis (Xiong et al, 2010). Indeed, OPCs in the cerebral cortex shift from a parenchymal to a perivascular subtype.…”

Oligodendrocyte Physiology and Pathology Function

“…Examples are metachromatic leukodystrophies, Canavan disease or X-linked adrenoleukodystrophy. Beyond this, the de- and regeneration of oligodendrocytes appears to be an important pathological aspect of many other neuronal disorders including spinal cord injury, where remyelination improves functional recovery [ 33 ], Alzheimer’s disease, where myelination-related processes are recurrently perturbed in multiple cell types, suggesting that myelination has a key role in Alzheimer’s disease pathophysiology [ 34 ], or stroke, where it is believed that oligodendrocyte progenitor cells can promote angiogenesis [ 35 ]. Beyond this, it has recently been suggested that cells of the oligodendrocyte lineage can transform, under specific conditions, into antigen-presenting cells, suggesting that oligodendrocytes can act as active immunomodulators [ 36 ].…”