SPHK1 and brain ischemia: By contrast, SphK1-driven autophagy in microglia exacerbates neuronal apoptosis and expands infarct volume by activating the TRAF2 pathway following cerebral ischemia–reperfusion, identifying SphK1 as a pro-inflammatory autophagy regulator [62] Moreover, both pharmacological and genetic inhibition of autophagy—such as via 3-MA treatment or Beclin-1 knockout—unexpectedly intensify microglial inflammatory responses and aggravate secondary brain injury [64,65].