Abstract
Aquaporin-4 (AQP-4), the most important water channel in the brain, is expressed by astrocyte end feet abutting microvessels. Altered expression levels of AQP-4 and redistribution of the protein throughout the membranes of cells found in glioblastoma multiforme (GBM) lead to development of the edema often found surrounding the tumor mass. Dysregulation of AQP-4 also occurs in hippocampal sclerosis and cortical dysplasia in patients with refractory partial epilepsy. This work reports on analysis of the relationship between AQP-4 expression and the incidence of epileptic seizures in patients with GBM. Immunohistochemical and polymerase chain reaction techniques were used to evaluate AQP-4 in biopsy specimens from 19 patients with GBM, 10 of who had a history of seizures before surgery. AQP-4 mRNA levels were identical in the two groups of patients, but AQP-4 expression was more frequently detected on the GBM membranes from specimens of patients with seizures than from individuals without (10 versus 2, P < 0.001). We conclude that reduced expression of cell surface AQP-4 is characteristic of GBM patients without seizures, likely attributable to a posttranslational mechanism.
Highlights
Epileptic seizures complicate the clinical course of approximately 20–40% of patients with glioblastoma multiforme (GBM) [1,2,3]
Aquaporins (AQPs) are hydrophobic integral membrane proteins that act as water channels and contribute to maintaining proper homeostasis of fluids in various cells and tissues
Large tumor size and increased age seem to be associated with reduced risk [1].The current study investigated whether variations of AQP-4 expression on GBM cell membrane might be linked to the pathogenesis of seizures in GBM
Summary
Epileptic seizures complicate the clinical course of approximately 20–40% of patients with glioblastoma multiforme (GBM) [1,2,3]. The pathogenesis of the seizures associated with malignant intracranial glial tumors is still uncertain and probably differs between GBM and other glial tumors [2]. AQP-4 is the most widely expressed member of the AQP family in the brain [5], where it plays a crucial role in the control of extracellular space volume. Disruption of AQP-4 expression on astrocytes was associated with edema in brain tumors, including GBM [6,7]. Dysregulation of AQP-4 expression was increasingly associated with epilepsy [8,9,10].
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