Vitamin B6 modulates microglial phagocytosis after hemorrhagic stroke

Myelin debris and apoptotic cells generated after intracerebral hemorrhage (ICH) contribute to inflammatory responses and hinder recovery. Efficient clearance of cellular debris by microglia is indispensable for neurological recovery and functional restoration. In this study, we demonstrate that pyridoxal (PL), a form of vitamin B6, plays a pivotal role in enhancing microglial phagocytic activity. Using an ICH mouse model, we found that vitamin B6 deficiency increased the accumulation of demyelinated myelin basic protein (dMBP) and elevated cell death, whereas PL supplementation significantly reduced the dMBP-positive area and the burden of apoptotic cells, thereby improving neurological function. Furthermore, knockout of pyridoxal kinase (Pdxk) in oligodendrocytes improved neurological recovery after ICH. Mechanistically, Pdxk knockout in oligodendrocytes upregulated interleukin-33 (Il33) secretion, thereby promoting microglial phagocytosis. Blocking the Il33 receptor with neutralizing antibodies abolished the protective effects of Pdxk deletion, whereas administration of recombinant Il33 in ICH mice enhanced debris clearance and functional recovery. Collectively, our findings suggest that oligodendrocyte Pdxk may represent a key therapeutic target for enhancing recovery after ICH through Il33-mediated modulation of microglial function.