The blood-brain barrier and epilepsy.
During the past several years, there has been increasing interest in the role of the blood-brain barrier (BBB) in epilepsy. Advances in neuroradiology have enhanced our ability to image and study the human cerebrovasculature, and further developments in the research of metabolic deficiencies linked to seizure disorders (e.g., GLUT1 deficiency), neuroinflammation, and multiple drug resistance to antiepileptic drugs (AEDs) have amplified the significance of the BBB's relationship to epilepsy. Prior to 1986, BBB research in epilepsy focused on three main areas: ultrastructural studies, brain glucose availability and transport, and clinical uses of AEDs. However, contrast-based imaging techniques and medical procedures such as BBB disruption provided a framework that demonstrated that the BBB could be reversibly disrupted by pathologic or iatrogenic manipulations, with important implications in terms of CNS drug delivery to "multiple drug resistant" brain. This concept of BBB breakdown for therapeutic purposes has also unveiled a previously unrecognized role for BBB failure as a possible etiologic mechanism in epileptogenesis. Finally, a growing body of evidence has shown that inflammatory mechanisms may participate in the pathological changes observed in epileptic brain, with increasing awareness that blood-borne cells or signals may participate in epileptogenesis by virtue of a leaky BBB. In this article we will review the relationships between BBB function and epilepsy. In particular, we will illustrate consensus and divergence between clinical reality and animal studies.
Oby
Emily
E
Cleveland Clinic Foundation, Department of Neurological Surgery, Cerebrovascular Research, Ohio 44195, USA.
Janigro
Damir
D
D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018432:Drug Resistance, Multiple / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D051381:Rats
D000927:Anticonvulsants