Neurovascular unit impairment in iron deficiency anemia

Iron is one of the crucial elements for CNS development and function and its deficiency (ID) is the most common worldwide nutrient deficit in the world. Iron deficiency anemia (IDA) in pregnant women and infants is a worldwide health problem due to its high prevalence and its irreversible long-lasting effects on brain development. Even with iron supplementation, IDA during pregnancy and/or breastfeeding can result in irreversible cognitive, motor, and behavioral impairments. The neurovascular unit (NVU) plays an important role in iron transport within the CNS as well as in the blood brain-barrier (BBB) formation and maturation, vasculogenesis/angiogenesis, neurovascular coupling and metabolic waste clearance. In animal models of IDA, significant changes have been observed at the capillary level, including alterations in iron transport, vasculogenesis, astrocyte endfeet, and pericytes. Despite these findings, the role of the NVU in IDA remains poorly understood. This review summarizes the potential effects of ID/IDA on brain development, myelination and neuronal function and discusses the role of NVU cells in iron metabolism, BBB, vasculogenesis/angiogenesis, neurovascular coupling and metabolic waste clearance. Furthermore, it emphasizes the need to view the NVU as a whole and as a potential target for ID/IDA. However, it remains unclear to what extent NVU alterations contribute to neuronal dysfunction, myelination abnormalities, and synaptic disturbances described in IDA.