Microglia at the blood-brain barrier (BBB) in health and disease. Front. Cell. Neurosci. 18:1360195. doi: 10.3389/fncel.2024.1360195. © 2024 Mayer and Fischer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. The blood-brain barrier (BBB) is a highly regulated structure that maintains brain homeostasis by selectively preventing the entry of substances from the peripheral blood into the central nervous system (CNS). Composed of endothelial cells, pericytes, and astrocytes, the BBB plays a crucial role in protecting the brain from harmful substances and maintaining the integrity of the CNS. Microglia, the resident macrophages of the brain, interact with the BBB and play a significant role in modulating the activation state of cells comprising the BBB, as well as microglia and perivascular macrophages themselves. Alterations in systemic metabolic and inflammatory states can promote endothelial cell dysfunction, reducing BBB integrity and allowing peripheral blood factors to leak into the CNS, potentially triggering neuroinflammation. Microglia are multifunctional cells that contribute to various aspects of brain function, including brain development, learning and memory, and the maintenance of CNS homeostasis. They continuously survey the brain by extending long processes that allow them to assess changes in the microenvironment. Microglia also interact with brain vascular endothelial cells and play a role in regulating the movement of solutes, chemicals, and foreign antigens into the brain parenchyma. In the context of metabolic dysfunction and inflammation, endothelial cells forming the BBB exhibit heightened levels of adhesion and transmigration molecules, which can contribute to BBB instability. Microglia are also involved in the regulation of cerebral blood flow through their interactions with endothelial cells and other vascular components. In the context of stroke, microglia exhibit a critical balance between protective and detrimental roles in neuroinflammation and BBB integrity. The activation of microglia can lead to increased BBB permeability and vascular leakage, potentially contributing to neuroinflammation and brain injury. However, microglia also play a protective role by limiting the infiltration of peripheral factors into the CNS parenchyma and aiding in the recovery of BBB permeability. Diabetes mellitus is associated with increased risk for neurodegenerative diseases such as Alzheimer's disease, vascular dementia, and mild cognitive impairment. Hyperglycemia contributes to endothelial dysfunction, adversely affecting BBBMicroglia at the blood-brain barrier (BBB) in health and disease. Front. Cell. Neurosci. 18:1360195. doi: 10.3389/fncel.2024.1360195. © 2024 Mayer and Fischer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. The blood-brain barrier (BBB) is a highly regulated structure that maintains brain homeostasis by selectively preventing the entry of substances from the peripheral blood into the central nervous system (CNS). Composed of endothelial cells, pericytes, and astrocytes, the BBB plays a crucial role in protecting the brain from harmful substances and maintaining the integrity of the CNS. Microglia, the resident macrophages of the brain, interact with the BBB and play a significant role in modulating the activation state of cells comprising the BBB, as well as microglia and perivascular macrophages themselves. Alterations in systemic metabolic and inflammatory states can promote endothelial cell dysfunction, reducing BBB integrity and allowing peripheral blood factors to leak into the CNS, potentially triggering neuroinflammation. Microglia are multifunctional cells that contribute to various aspects of brain function, including brain development, learning and memory, and the maintenance of CNS homeostasis. They continuously survey the brain by extending long processes that allow them to assess changes in the microenvironment. Microglia also interact with brain vascular endothelial cells and play a role in regulating the movement of solutes, chemicals, and foreign antigens into the brain parenchyma. In the context of metabolic dysfunction and inflammation, endothelial cells forming the BBB exhibit heightened levels of adhesion and transmigration molecules, which can contribute to BBB instability. Microglia are also involved in the regulation of cerebral blood flow through their interactions with endothelial cells and other vascular components. In the context of stroke, microglia exhibit a critical balance between protective and detrimental roles in neuroinflammation and BBB integrity. The activation of microglia can lead to increased BBB permeability and vascular leakage, potentially contributing to neuroinflammation and brain injury. However, microglia also play a protective role by limiting the infiltration of peripheral factors into the CNS parenchyma and aiding in the recovery of BBB permeability. Diabetes mellitus is associated with increased risk for neurodegenerative diseases such as Alzheimer's disease, vascular dementia, and mild cognitive impairment. Hyperglycemia contributes to endothelial dysfunction, adversely affecting BBB