Other
13 Authors
- Ye Q,
- Wang CY,
- Oh H,
- Chen Z,
- Kim KI,
- Zhan J,
- Lee HK,
- Reshetnyak YK,
- D'Alessandro A,
- Choy TJ,
- Jung SY,
- Marrelli SP,
- Jo J
| First Author | Ye Q | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 5 | Pages | 114193 |
| PubMed ID | 38709635 | Mgi Jnum | J:350670 |
| Mgi Id | MGI:7658752 | Doi | 10.1016/j.celrep.2024.114193 |
| Citation | Ye Q, et al. (2024) Astrocytic Slc4a4 regulates blood-brain barrier integrity in healthy and stroke brains via a CCL2-CCR2 pathway and NO dysregulation. Cell Rep 43(5):114193 |
| abstractText | Astrocytes play vital roles in blood-brain barrier (BBB) maintenance, yet how they support BBB integrity under normal or pathological conditions remains poorly defined. Recent evidence suggests that ion homeostasis is a cellular mechanism important for BBB integrity. In the current study, we investigated the function of an astrocyte-specific pH regulator, Slc4a4, in BBB maintenance and repair. We show that astrocytic Slc4a4 is required for normal astrocyte morphological complexity and BBB function. Multi-omics analyses identified increased astrocytic secretion of CCL2 coupled with dysregulated arginine-NO metabolism after Slc4a4 deletion. Using a model of ischemic stroke, we found that loss of Slc4a4 exacerbates BBB disruption, which was rescued by pharmacological or genetic inhibition of the CCL2-CCR2 pathway in vivo. Together, our study identifies the astrocytic Slc4a4-CCL2 and endothelial CCR2 axis as a mechanism controlling BBB integrity and repair, while providing insights for a therapeutic approach against BBB-related CNS disorders. |
