Expressions of glutathione S-transferase alpha, mu, and pi in brains of medically intractable epileptic patients

Three different GST isoforms (α, μ, and π) were detected with immunohistochemistry. GST-α expression was not seen in any cortex specimens. Sixty three percent (63%) of control and 53% of intractible epileptic specimens showed GST-μ immunoreactivity. No significant difference in intensity of GST-μ staining was observed between these two groups. GST-π expression was found in endothelial cells and glial cells/astrocytes. Fifty percent (50%) of the control patients and 66% of the epileptic patients were GST-π positive. The grading of epileptic patients was significantly higher than that of control patients (p < 0.01).High levels of GST-π in endothelial cells and glial cells/astrocyte correlate to medical intractable epilepsy, suggesting that GST-π contributes to resistance to AED treatment.Epilepsy is a common neurological disorder, affecting approximately 1 to 2% of the population [1]. The majority of epileptic patients are successfully treated with anti-epileptic drugs (AEDs). Nevertheless, about 20–25% of epileptic patients, as defined as medically intractable epilepsy, fail to respond to AEDs [2].AEDs can prevent abnormal neuronal firing and seizure spread at seizure focus. The enzymatic activity of Glutathione S-transferases (GSTs) in liver plays an essential role in metabolizing and clearing AEDs [3-5]. GSTs are a group of phase II enzymes of defense that catalyze the conjugation of reduced glutathione to a wide range of electrophiles [6]. There are eight isoforms of soluble GST (α, μ, π, θ, ω, ζ, σ, and κ) and at least three membrane bound GST isoforms (MGST1, MGST2 and MGST3) [7,8]. GSTs are widely expressed in almost every tissue, while some isoforms show tissue-specific distribution. In mammals, expression of GST-α, μ, and π in CNS was reported [9-12]. In the present study, it is hypothesized that higher levels of GSTs in brain, especially in brain-blood barrier may result in poor intraparenchymal accumulation of AEDs, and lead to medical intractability. There