Age dependency of trauma-induced neocortical epileptogenesis

Igor Timofeev, Terrence J. Sejnowski, Maxim Bazhenov, Sylvain Chauvette, Laszlo B. Grand

Trauma and brain infection are the primary sources of acquired epilepsy, which can occur at any age and may account for a high incidence of epilepsy in developing countries. We have explored the hypothesis that penetrating cortical wounds cause deafferentation of the neocortex, which triggers homeostatic plasticity and lead to epileptogenesis (Houweling etal., 2005). In partial deafferentation experiments of adult cats, acute seizures occurred in most preparations and chronic seizures occurred weeks to months after the operation in 65% of the animals (Nita etal., 2006,2007; Nita and Timofeev, 2007). Similar deafferentation of young cats (age 8-12 months) led to some acute seizures, but we never observed chronic seizure activity even though there was enhanced slow-wave activity in the partially deafferented hemisphere during quiet wakefulness. This suggests that despite a major trauma, the homeostatic plasticity in young animals was able to restore normal levels of cortical excitability, but in fully adult cats the mechanisms underlying homeostatic plasticity may lead to an unstable cortical state. To test this hypothesis we made an undercut in the cortex of an elderly cat. After several weeks this animal developed seizure activity. These observations may lead to an intervention after brain trauma that prevents epileptogenesis from occurring in adults.