- Epilepsy of the temporal lobe (TLE) is the most common form of focal epilepsy, and in adults, it most frequently develops after injury. However, the mechanisms by which a normal functioning brain turns into an epileptic one still remain obscure. Recent studies point to vascular involvement and particularly blood-brain barrier (BBB) dysfunction in the development of epilepsy. The BBB is a specialized structure which functions to control the neuronal extracellular milieu. BBB dysfunction is found in many diseases of the central nervous system, including stroke, traumatic injuries, tumors and infections. Interestingly, all these insults may initiate an epileptogenic process which eventually leads to spontaneous, recurrent seizures. This epileptogenic time frame usually lasts weeks, months, or even years in man, and days to weeks in rodents and may serve as a “window of opportunity” for the prevention of epilepsy. However, no prevention strategy exists, stressing the importance of research into the mechanisms of epileptogenesis. Here, we will underscore recent experiments suggesting that BBB dysfunction directly induces epileptogenesis. We will provide new evidence to support the hypothesis that BBB breakdown and specifically exposure of temporal lobe structures to the most common serum protein, albumin, is sufficient to induce epileptogenesis.