Seizure-induced neuronal injury: animal data.

One of the oldest questions in epilepsy is whether seizures are a cause or a result of brain damage. Animal data have provided us with insights into the relationship between seizures and subsequent brain damage. It is now recognized that seizures can be caused by brain injury and that, in certain conditions, can cause brain damage. Whether seizures result in brain damage depends on a number of variables, including age of the animal, seizure type and duration, etiology of the seizures, and genetic substrate on which the seizures occur. Seizures lasting for hours can cause injury to the brain regardless of whether they are generalized or focal in onset. The cell loss that occurs after the seizure is secondary to excessive excitability, with seizures causing massive depolarization of neurons leading to excessive glutamate release. This glutamate release results in increased intracellular calcium, causing a cascade of changes that ultimately result in cell death. Hypoxia and ischemia can exacerbate the injury. However, even in animals that are well ventilated and oxygenated, prolonged seizures can lead to cell loss and subsequent reorganization of synaptic networks. Although prolonged seizures at any age can result in cell loss, the immature brain fares much better than the mature brain with regard to cell loss after a prolonged seizure. Evidence that prolonged seizures result in neuronal loss is firmly established. It is less clear how detrimental recurrent seizures are. Although cell loss and synaptic reorganization have been reported in recurrent seizure models, such as kindling, it is generally modest compared to status epilepticus. When seizure-induced changes do occur, the pathologic patterns in the brain differ from those in status epilepticus.