Neuroinflammation in epilepsy: Mitochondrial connections and therapeutic targets

Epilepsies impact approximately 65 million people worldwide. Clinical management can be difficult – approximately one third of patients fail to respond to existing antiseizure drugs. Neuroinflammation has been implicated in epileptogenesis in animal and clinical studies and is often associated with mitochondrial dysfunction. Seizures are common among patients with primary genetic mitochondrial diseases. Neuroinflammation is commonly reported in mitochondrial diseases where neurologic dysfunction is present, including seizures, and recent findings show that at least some seizures in mitochondrial disease can be prevented by immune suppressing interventions. Existing anti-seizure therapies generally target neuronal functions without addressing potential underlying inflammatory etiology, while inflammatory mediators provide new candidates for intervention. Here, we detail evidence linking inflammation to epilepsy, with an emphasis on epilepsies linked to mitochondrial dysfunction, and discuss as the therapeutic potential of anti-inflammatory interventions in epilepsies. • Neuroinflammation has been implicated in epileptogenesis in animal and clinical studies • Neuroinflammation is often associated with mitochondrial dysfunction • Seizures and neuroinflammation are common among patients with primary genetic mitochondrial diseases • Inflammatory factors mediating the pathogenesis of epilepsy may provide novel candidates for intervention