Drug resistance in epilepsy: human epilepsy.
The basis of drug resistance in human epilepsy is not understood. Parallels with resistance in cancer suggest that drug resistance proteins may have a role. To examine this possibility, we have studied human brain tissue containing pathologies capable of causing refractory epilepsy. Using immunohistochemistry for P glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1), we examined both pathological tissue and control tissue. We demonstrate expression of Pgp and MRP1 in glia from cases of malformation of cortical development studied both before and after the onset of epilepsy, as well as in cases of hippocampal sclerosis and dysembryoplastic neuroepithelial tumours. In one particular type of malformation, we also demonstrate that dysplastic neurons express MRP1. The pattern of immunolabelling suggests overexpression is concentrated particularly around vessels in most of the pathologies. The timing shows that expression may be constitutive in some pathologies. These findings suggest that drug resistance proteins may contribute to drug resistance in refractory epilepsy.
Sisodiya
S M
SM
University Department of Clinical Neurology, Institute of Neurology, University College London, UK.
Lint
W R
WR
Harding
B N
BN
Squier
M V
MV
Thom
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000737:chemistry / Q000473:pathology; D002540:Cerebral Cortex / Q000002:abnormalities; D004351:Drug Resistance / Q000502:physiology; D018432:Drug Resistance, Multiple; D004828:Epilepsies, Partial / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis* / Q000502:physiology; D009363:Neoplasm Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000502:physiology; D018242:Neuroectodermal Tumors, Primitive / Q000737:chemistry / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism; D012598:Sclerosis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000927:Anticonvulsants; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins