Control of scar formation in experimentally induced epilepsy

Abstract

Penfield proposed that the meningocerebral scar that forms following trauma to the brain plays an important role in the development of posttraumatic epilepsy. Although the epileptogenic scar has come to be widely accepted as a cause of epilepsy, there is no direct evidence that scar formation contributes to epileptogenesis. This current study showed that procedures that control the development of collagen in a fibroblastic scar may modify the development of epilepsy. Epilepsy induced in the guinea pig by injection of metallic aluminum powder into the cerebral cortex was used as a model of posttraumatic epilepsy. Following application of aluminum and implantation of epidural electrodes, animals received either daily injections of prednisolone or an ascorbic acid-deficient diet to block scar formation. Control animals also had an injection of aluminum, but afterward received saline injections or a normal diet. Control animals developed epileptic spikes and often exhibited focal seizures. All manifestations of epileptogenesis were markedly reduced in animals treated with prednisolone or the ascorbic acid-deficient diet. The reduction in epileptiform activity corresponded to reduced collagenous scar formation in the treated animals. Although effective when given prophylactically, prednisolone did not inhibit the activity of an already established epileptic focus whether induced by aluminum or by amygdala kindling, nor did it block pentylenetetrazol-induced seizures. The finding that epileptogenesis is blocked by two procedures that inhibit scar formation but show no evidence of a direct anticonvulsant effect, suggests that scar formation is a significant factor in epileptogenesis induced by metallic aluminum. The collagenous component appears to be more significant than the glial component of the scar.