By Z. Afawi
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Additional resources for Clinical and Genetic Aspects of Epilepsy
1 Blood-brain barrier anatomy Numbers and Facts. The blood-brain barrier is a network of brain capillaries (microvessels). , 2003). The microvasculature in the human brain is comprised of about 100 billion capillaries forming a highly branched vascular network 25 The Blood-Brain Barrier in Epilepsy (Zlokovic & Apuzzo, 1998). , 2003). This ensures that every neuron (about 100 billion in human brain) is in contact with and perfused by its own capillary, which allows efficient nutrient and oxygen supply.
Although this comparison is flawed, inhibiting P-gp increased phenytoin permeation in the AED-resistant cells. , 2007). Using a drug-resistant epilepsy rat model, Potschka et al. , 2004). van Vliet et al. , 2006). Marchi et al. , 2005). , 2007). In addition to P-gp, data indicate that BCRP plays a significant role in drug efflux at the blood-brain barrier. , 2007). However, little information is available on the extent to which BCRP contributes to AED resistance and if Pgp and BCRP work in concert in AED efflux from the brain.
Whether targeting any of the other pathways could be used as a therapeutic strategy in AED-resistant epilepsy is unknown and remains to be determined. , 2002)), but the signalling that upregulates Mrp2 in epilepsy is unknown. , 2000). , 2008). , 2010). , 2009; Zhu & Liu, 2004)). , 1992; Ueda & Tsuru, 1995). Zhu and Liu were the first to connect glutamate with P-gp upregulation at the blood-brain barrier. They found that glutamate increased P-gp expression and activity in rat brain microvessel endothelial cells and suggested that activation of the NMDAR plays a critical role in glutamate-mediated P-gp upregulation (Zhu & Liu, 2004).
Clinical and Genetic Aspects of Epilepsy by Z. Afawi