Animal Models of Acquired Epilepsy and Tauopathies

The tauopathies are a group of neurodegenerative diseases in which aggregates of the hyperphosphorylated form of the microtubule-associated protein, tau, are believed to play a critical role in the pathogenesis. Many of the tauopathies are associated with an increased incidence of development of epilepsy. Deposits of hyperphosphorylated tau have also been documented pathologically in animal models of epilepsy, and in patients with drug-resistant focal epilepsy who have undergone epilepsy surgery. Pathological aggregates of hyperphosphorylated tau can occur in either primary neurodegenerative conditions, such as Alzheimer's disease (AD), or develop following an acquired brain insult, such as traumatic brain injury. The precise mechanisms by which hyperphosphorylated tau contributes to epileptogenesis are currently uncertain, but there is increasing evidence from animal models that targeting tau-based mechanism, either genetically or pharmacologically, can have both antiseizure and antiepileptogenic effects. This chapter will provide an overview of animal models of epilepsy-associated tauopathies, biomarkers of tau pathology, experimental evidence implicating hyperphosphorylated tau in the pathophysiology of acquired epilepsies, and the promise of tau-related therapies to prevent and treat acquired epilepsy.