Astroglial Networks and Implications for Therapeutic Neuromodulation of Epilepsy

Mark R. Witcher, Thomas L. Ellis

Epilepsy is a common chronic neurologic disorder affecting approximately 1% of the world population. More than one-third of all epilepsy patients have incompletely controlled seizures or debilitating medication side effects in spite of optimal medical management. Medically refractory epilepsy is associated with excess injury and mortality, psychosocial dysfunction, and significant cognitive impairment. Effective treatment options for these patients can be limited. The cellular mechanisms underlying seizure activity are incompletely understood, though we here describe multiple lines of evidence supporting the likely contribution of astroglia to epilepsy, with focus on individual astrocytes and their network functions. Of the emerging therapeutic modalities for epilepsy, one of the most intriguing is the field of neuromodulation. Neuromodulatory treatment, which consists of administering electrical pulses to neural tissue to modulate its activity leading to a beneficial effect, may be an option for these patients. Current modalities consist of vagal nerve stimulation, open and closed-loop stimulation, and transcranial magnetic stimulation. Due to their unique properties, we here present astrocytes as likely important targets for the developing field of neuromodulation in the treatment of epilepsy.