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Over-expression of P-glycoprotein in malformations of cortical development

S M Sisodiya1, J Heffernan, M V Squier

  • 1Epilepsy Research Group, Institute of Neurology, University College London, UK.

Neuroreport
|December 22, 1999
PubMed

Insights

Malformations of cortical development (MCD) in epilepsy may cause drug resistance due to P-glycoprotein over-expression. This study found constitutive P-glycoprotein in many MCD brain samples before seizure onset or treatment.

Area of Science:

  • Neuroscience
  • Epilepsy Research
  • Molecular Biology

Background:

  • Drug resistance in epilepsy associated with malformations of cortical development (MCD) remains poorly understood.
  • P-glycoprotein is a known mediator of drug resistance.
  • The hypothesis is that MCD lesions exhibit P-glycoprotein over-expression.

Purpose of the Study:

  • To investigate the expression of P-glycoprotein in brain samples from individuals with MCD.
  • To determine if P-glycoprotein over-expression is a constitutive feature in MCD, independent of antiepileptic drug (AED) treatment.

Main Methods:

  • Immunohistochemistry was used to examine brain tissue samples.
  • Samples were obtained from 16 MCD cases and 16 age-matched controls.
  • Analysis focused on glial P-glycoprotein labeling before seizure onset or AED treatment.

Main Results:

  • Over-expression of P-glycoprotein, indicated by glial labeling, was observed in 10 out of 16 MCD samples.
  • This contrasts with only two out of 16 control samples showing similar labeling (p = 0.003).
  • Semiquantitative assessment revealed numerous immunoreactive glia in five MCD cases versus one control.

Conclusions:

  • The study concludes that constitutive over-expression of P-glycoprotein is present in a significant proportion of MCD cases.
  • This finding suggests a potential mechanism for drug resistance in epilepsy related to MCD.

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