Parenchymal changes related to plasma protein extravasation in experimental seizures

To determine whether the transient opening of the blood-brain barrier (BBB) during epileptic seizures may lead to permanent neuronal changes, seizures of a few minutes' duration were induced by intravenous (i.v.) administration of 0.3 mg/kg bicuculline to conscious rats with indwelling catheters for blood pressure (BP) and blood gas monitoring. The rats were killed 5 min to 7 days later, and the distribution of endogenous plasma albumin, fibrinogen, and fibronectin in the brain was studied by immunohistochemistry. Parallel sections were scrutinized for evidence of light-microscopic structural changes in the tissue. Extensive multifocal extravasation of plasma proteins throughout the brain and brainstem was observed. The original clearly focal distribution became more diffuse with prolongation of the recovery time. In addition, the intensity of the immunoreactivity decreased, most likely due to drainage into the cerebrospinal fluid (CSF) in the ventricles and the subarachnoidal space of the extravasated proteins, but some antialbumin-positive material was still visible after 7 days. In areas with extravasation, many nerve cells, especially cerebellar Purkinje cells, became strongly positive for albumin. In some of these areas, neurons appeared to be irreversibly injured. Thus, considerable amounts of plasma proteins are extravasated even during short epileptic seizures, and albumin appear to remain in the tissue for a long time, especially in Purkinje cells. The Purkinje cell loss in chronic epilepsy may be caused partly by cumulative bouts of plasma extravasations.