There remains a need for more efficacious treatments for
status epilepticus. Prolonged
seizures result in the release of
ATP from cells which activates the P2 class of ionotropic and metabotropic
purinoceptors. The P2X receptors gate depolarizing
sodium and
calcium entry and are expressed by both neurons and glia throughout the brain, and a number of subtypes are upregulated after
status epilepticus. Recent studies have explored the in vivo effects of targeting
ATP-gated P2X receptors in preclinical models of
status epilepticus, with particular focus on the
P2X7 receptor (P2X7R). The P2X7R mediates microglial activation and the release of the proepileptogenic inflammatory
cytokine interleukin 1β. The receptor may also directly modulate neurotransmission and gliotransmission and promote the recruitment of immune cells into brain parenchyma. Data from our group and collaborators show that
status epilepticus produced by intraamygdala microinjection of
kainic acid increases P2X7R expression in the hippocampus and neocortex of mice. Antagonism of the P2X7R in the model reduced seizure severity, microglial activation and
interleukin 1β release, and neuronal injury. Coadministration of a P2X7R antagonist with a
benzodiazepine also provided seizure suppression in a model of drug-refractory
status epilepticus when either treatment alone was minimally effective. More recently, we showed that
status epilepticus in immature rats is also reduced by P2X7R antagonism. Together, these findings suggest that P2X receptors may be novel targets for seizure control and interruption of
neuroinflammation after
status epilepticus. This article is part of a Special Issue entitled "
Status Epilepticus".