Mitochondrial dysfunction and oxidative stress: a contributing link to acquired epilepsy?

Abstract

Mitochondrial dysfunction and oxidative stress contribute to several neurologic disorders and have recently been implicated in acquired epilepsies such as temporal lobe epilepsy (TLE). Acquired epilepsy is typically initiated by a brain injury followed by a "latent period" whereby molecular, biochemical and other cellular alterations occur in the brain leading to chronic epilepsy. Mitochondrial dysfunction and oxidative stress are emerging as factors that not only occur acutely as a result of precipitating injuries such as status epilepticus (SE), but may also contribute to epileptogenesis and chronic epilepsy. Mitochondria are the primary site of reactive oxygen species (ROS) making them uniquely vulnerable to oxidative damage that may affect neuronal excitability and seizure susceptibility. This mini-review provides an overview of evidence suggesting the role of mitochondrial dysfunction and oxidative stress as acute consequences of injuries that are known to incite chronic epilepsy and their involvement in the chronic stages of acquired epilepsy.

Fig. 1

Time-course of mitochondrial oxidative stress and subsequent damage during epileptogenesis. Note the initial and persistent decrease in mitochondrial and tissue redox status (CoASH/CoASSG, GSH/GSSG) throughout epileptogenesis which may serve an ongoing link to chronic epilepsy