Astroglial Scarring and Seizures: A Cell Biological Perspective on Epilepsy

Epilepsy is among the most prevalent chronic neurological diseases and affects an estimated 2.2 million people in the United States alone. About one third of patients are resistant to currently available antiepileptic drugs, which are exclusively targeting neuronal function. Yet, reactive astrocytes have emerged as potential contributors to neuronal hyperexcitability and seizures. Astrocytes react to any kind of CNS insult with a range of cellular adjustments to form a scar and protect uninjured brain regions. This process changes astrocyte physiology and can affect neuronal network function in various ways. Traumatic brain injury and stroke, both conditions that trigger astroglial scar formation, are leading causes of acquired epilepsies and surgical removal of this glial scar in patients with drug-resistant epilepsy can alleviate the seizures. This review will summarize the currently available evidence suggesting that epilepsy is not a disease of neurons alone, but that astrocytes, glial cells in the brain, can be major contributors to the disease, especially when they adopt a reactive state in response to central nervous system insult.