Hydrogen Alleviates Necroptosis and Cognitive Deficits in Lithium–Pilocarpine Model of Status Epilepticus

Status epilepticus without prompt seizure control always leads to neuronal death and long-term cognitive deficits, but effective intervention is still absent. Here, we found that hydrogen could alleviate the hippocampus-dependent spatial learning and memory deficit in lithium–pilocarpine model of status epilepticus in rats, as evidenced by the results in Morris water maze test. Hydrogen treatment downregulated the expression of necroptosis-related proteins, such as MLKL, phosphorylated-MLKL, and RIPK3 in hippocampus, and further protected neurons and astrocytes from necroptosis which was here first verified to occur in status epilepticus. Hydrogen also protected cells from apoptosis, which was indicated by the decreased cleaved-Caspase 3 expression. Meanwhile, Iba1⁺ microglial activation by status epilepticus was reduced by hydrogen treatment. These findings confirm the utility of hydrogen treatment in averting cell death including necroptosis and alleviating cognitive deficits caused by status epilepticus. Therefore, hydrogen may provide a potential and powerful clinical treatment for status epilepticus-related cognitive deficits.