Simultaneous inhibition of pannexin-1 by probenecid and caspases by Z-VAD-fmk attenuates apoptosis and necroptosis in a rat model of cerebral ischemia-reperfusion

Simultaneous inhibition of pannexin-1 and caspase activity provides superior neuroprotection in cerebral ischemia-reperfusion injury. This dual-targeting strategy effectively limits cell death and inflammation. Importantly, these findings may help explain the limited success of prior anti-apoptotic monotherapies in stroke and emphasize the necessity of targeting both apoptosis and necroptosis to achieve meaningful neuroprotection.