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By Z. Afawi

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Three critical components of barrier function 1) tight junctions, 2) metabolising enzymes and 3) transporter proteins - are introduced and we describe how they are changed in epilepsy and affected by epilepsy treatment. Recent efforts in blood-brain barrier research to overcome drug-resistant epilepsy are also discussed. 2. The blood-brain barrier The History of Blood-Brain Barrier Discovery. First experiments contributing to the discovery of the blood-brain barrier were performed by Paul Ehrlich in 1885 (Figure 1).

Neurosci Lett 217:29-32. Theodore WH, Carson RE, Andreasen P, Zametkin A, Blasberg R, Leiderman DB, Rice K, Newman A, Channing M, Dunn B, et al. (1992) PET imaging of opiate receptor binding in human epilepsy using [18F]cyclofoxy. Epilepsy Res 13:129-139. Tooyama I, Bellier JP, Park M, Minnasch P, Uemura S, Hisano T, Iwami M, Aimi Y, Yasuhara O, Kimura H (2002) Morphologic study of neuronal death, glial activation, and progenitor cell division in the hippocampus of rat models of epilepsy. Epilepsia 43 Suppl 9:39-43.

Third, since transporter upregulation in epilepsy has been linked to increased seizure occurrence, prevention of transporter upregulation holds the promise of better seizure control. Thus, mapping the signalling pathways involved in efflux transporter upregulation at the bloodbrain barrier in epilepsy can help identify new targets that may potentially be used to overcome transporter-mediated AED resistance and improve seizure treatment. Several signalling pathways have been identified that regulate P-gp, BCRP, and Mrp2 at the blood-brain barrier.

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