Fig. 9
Schematic illustration of NHE-1-mediated pHi and signaling regulation in microglial cells and communication with oligodendrocytes in ischemic white matter repair. Using single cell RNAseq, we discovered that selective deletion of microglial Nhe1 acidified microglia and activated CREB signaling with increased BDNF secretion, and elevated SPP1 signaling pathway, which enhanced the restorative microglia-oligodendrocyte interactions in support of white matter remyelination. Our findings identified a novel group of stroke-associated white matter microglia, which can be activated by acidifying microglial pHi through blocking the NHE1 protein. Regulating microglial pHi presents a possible mechanism in promoting the beneficial microglia-oligodendrocyte interactions in improving white matter myelination after ischemic stroke