Preclinical Testing Strategies for Epilepsy Therapy Development.

The development of antiepileptogenic and disease-modifying treatments for epilepsy is a key goal of epilepsy research. Technological and scientific advances over the past two decades have seen the development of numerous therapeutic approaches, many of which show great promise in animal models. To facilitate and de-risk the translation of these promising approaches, however, rigorous preclinical testing is needed.

Somatostatin interneuron fate-mapping and structure in a Pten knockout model of epilepsy.

Disruption of inhibitory interneurons is common in the epileptic brain and is hypothesized to play a pivotal role in epileptogenesis. Abrupt disruption and loss of interneurons is well-characterized in status epilepticus models of epilepsy, however, status epilepticus is a relatively rare cause of epilepsy in humans. How interneuron disruption evolves in other forms of epilepsy is less clear.

Behavioral and Cognitive Consequences of Spreading Depolarizations: A Translational Scoping Review.

Spreading depolarizations (SDs) are self-propagating waves of mass depolarization that cause silencing of brain activity and have the potential to impact brain function and behavior. In the eight decades following their initial discovery in 1944, numerous publications have studied the cellular and molecular underpinning of SDs, but fewer have focused on the impact of SDs on behavior and cognition. It is now known that SDs occur in more than 60% of patients with moderate-to-severe traumatic brain injury (TBI), and their presence is associated with poor 6-month outcomes.