Affiliation:
1. Department of Neurology, Mental and Neurological Disease Research Center The Third Affiliated Hospital of Sun Yat‐sen University Guangzhou China
2. Guangdong Provincial Key Laboratory of Brain Function and Disease Guangzhou China
Abstract
AbstractAimsHypoperfusion induces significant white matter injury in cerebral vascular disorders, including arteriosclerotic cerebral small vessel disease (aCSVD), which is prevalent among the elderly. Iron transport by blood vessel endothelial cells (BVECs) from the periphery supports oligodendrocyte maturation and white matter repair. This study aims to elucidate the association between iron homeostasis changes and white matter injury severity, and explore the crosstalk between BVECs and oligodendroglial lineage cells.MethodsIn vivo: C57BL/6 mice were subjected to unilateral common carotid artery occlusion (UCCAO). In vitro: BVECs with myelin pretreatment were co‐cultured with oligodendrocyte progenitor cells (OPCs) or organotypic cerebellar slices subjected to oxygen and glucose deprivation.ResultsCirculatory iron tends to be stored in aCSVD patients with white matter injury. Myelin debris endocytosis by BVECs impairs iron transport, trapping iron in the blood and away from the brain, worsening oligodendrocyte iron deficiency in hypoperfusion‐induced white matter injury. Iron accumulation in BVECs triggers ferroptosis, suppressing iron transport and hindering white matter regeneration. Intranasal holo‐transferrin (hTF) administration bypassing the BBB alleviates oligodendrocyte iron deficiency and promotes myelin regeneration in hypoperfusion‐induced white matter injury.ConclusionThe iron imbalance between BVECs and oligodendroglial lineage cells is a potential therapeutic target in hypoperfusion‐induced white matter injury.
Funder
National Natural Science Foundation of China
Guangzhou Municipal Science and Technology Program key projects
Guangzhou Municipal Science and Technology Project
Science and Technology Planning Project of Guangdong Province