Effects of baicalein pre-treatment on the NLRP3/GSDMD pyroptosis pathway and neuronal injury in pilocarpine-induced status epilepticus in the mice.

Status epilepticus (SE) links to high mortality and morbidity. Considering the neuroprotective property of baicalein (BA), we investigated its effects on post-SE neuronal injury via the NLRP3/GSDMD pathway. Mice were subjected to SE modeling and BA interference, with seizure severity and learning and memory abilities evaluated. The histological changes, neurological injury and neuron-specific enolase (NSE)-positive cell number in hippocampal CA1 region, and cell death were assessed. Levels of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3)/gasdermin-D (GSDMD) pathway-related proteins, inflammatory factors, and Iba-1+NLRP3+ and Iba-1+GSDMD-N+ cells were determined. BA ameliorated post-SE cognitive dysfunction and neuronal injury in mice, as evidenced by shortened escape latency, increased number of crossing the target quadrant within 60 s and the time staying in the target quadrant, alleviated hippocampal damage, increased viable cell number, decreased neuronal injury, and increased NSE-positive cells. Mechanistically, BA repressed microglial pyroptosis, reduced inflammatory factor release, and attenuated neuronal injury by inhibiting the NLRP3/GSDMD pathway. The NLRP3 inhibitor exerted similar effects as BA on SE mice, while the NLRP3 activator partially reversed BA-improved post-SE neuronal injury in mice. Conjointly, BA reduced microglial pyroptosis in hippocampal CA1 area by inhibiting the NLRP3/GSDMD pyroptosis pathway, thereby ameliorating post-SE neuronal injury in mice. This study highlights the ameliorative role of BA in neuronal injury via repression of the NLRP3/GSDMD pyroptosis pathway in SE mice, offering theoretical support for the treatment of SE using BA.