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Drug resistance in epilepsy: human epilepsy
S M Sisodiya1, W R Lint, B N Harding
1University Department of Clinical Neurology, Institute of Neurology, University College London, UK.
Abstract:
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.
Insights
Drug resistance proteins like P glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1) are expressed in brain tissue from epilepsy patients. This suggests their potential role in refractory epilepsy drug resistance.
Area of Science:
- Neuroscience
- Pharmacology
- Oncology
Background:
- The mechanisms underlying drug resistance in human epilepsy remain unclear.
- Drug resistance in cancer shares similarities, suggesting a role for drug resistance proteins.
Purpose of the Study:
- To investigate the potential role of drug resistance proteins in refractory epilepsy.
- To examine the expression of P glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1) in human brain tissue associated with epilepsy.
Main Methods:
- Immunohistochemistry was used to detect Pgp and MRP1 expression.
- Human brain tissue samples from epilepsy cases (malformation of cortical development, hippocampal sclerosis, dysembryoplastic neuroepithelial tumours) and controls were analyzed.
Main Results:
- Pgp and MRP1 were expressed in glia in various epilepsy-associated pathologies.
- Dysplastic neurons also showed MRP1 expression in a specific malformation type.
- Overexpression was often concentrated around blood vessels.
- Expression patterns suggest some pathologies may have constitutive Pgp and MRP1 expression.
Conclusions:
- The findings suggest that drug resistance proteins, Pgp and MRP1, may contribute to the development of drug resistance in refractory epilepsy.
- Further research is warranted to elucidate the precise role of these proteins in epilepsy treatment.
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