In chronic cobalt-induced experimental epilepsy in the cat, there are alterations in behavior, electroencephalograms, and brain sodium, potassium adenosine triphosphatase (Na, K ATPase) activity. The electrographic and enzymatic changes occur both in focus and homotopic cortex, and are time related. The onset of EEG paroxysms consistently precedes increases in Na,K ATPase activity, indicating that the enzymatic change is adaptive. Prophylactic treatment with phenytoin (formerly diphenylhydantoin) prevents these chronic alterations from developing, although some early changes do occur. After the drug is withdrawn following 28 days of therapy, treated animals still demonstrate no evidence of epileptiform discharges or changes in Na,K ATPase activity, although these changes persist in untreated cats. Given properly, phenytoin may prevent alterations in brain, which can result in the formation of a hyperexcitable population of cells. These data support the efficacy of early pharmacologic prophylaxis in posttraumatic epilepsy.
Rapport RL, Ojemann GA. Prophylactically Administered PhenytoinEffects on the Development of Chronic Cobalt-Induced Epilepsy in the Cat. Arch Neurol. 1975;32(8):539–548. doi:10.1001/archneur.1975.00490500059007