SPHK1 and ischemia: Post-ischemia, Tlr2 activation on microglia and neurons triggers divergent pathways: (1) neuronal MyD88/JNK-AP1 signaling induces caspase-3-dependent apoptosis through calcium dysregulation [25]; (2) microglial Tlr2/Sphk1 axis amplifies IL-1β/TNF-α release via S1P-mediated feedback, exacerbating neuroinflammation [26].