Figure 2.

A: Schematic illustration of glial iron metabolism. This hypothetical model illustrates the possible interactions between oligodendrocytes and astrocytes in iron metabolism during development as well as in the adult brain. (1) Most Tf in the brain is synthesized and secreted by OPCs and oligodendrocytes as apo‑Tf. (2) Astrocytes, OPCs and mature oligodendrocytes probably acquire most iron through TfR and holo‑Tf that is present in interstitial fluid and cerebrospinal fluid. (3) DMT1 can participate in Fe²⁺ absorption independent of the Tf cycle. (4) Ceruloplasmin can oxidize Fe²⁺ to Fe³⁺ and then promote ferroportin-mediated Fe²⁺ release in astrocytes, OPCs and mature oligodendrocytes. (5) Iron is stored in astrocytes, OPCs and myelinating oligodendrocytes mainly in the form of ferritin. Ferritin released from astrocytes could be the main mechanism of OPC and matue oligodendrocyte iron intake. B: Schematic representation of the neurovascular unit organization. DMT1: divalent metal transporter 1; OPC: oligodendrocyte progenitor cells.