Increased NKCC1 expression in arachnoid cysts supports secretory basis for cyst formation

Abstract

Arachnoid cysts (AC) are filled with liquid very similar to cerebrospinal fluid (CSF). The mechanisms of fluid accumulation have remained unknown; previous studies have however indicated both fluid secretion and a one-way valve as a mechanism. If the filling was caused by fluid secretion, mechanisms similar to those underlying CSF production would be anticipated. We have investigated the expression levels of all genes known to be involved in mammalian CSF production in surgically removed AC. Based on mRNA microarray analysis of AC and normal arachnoid tissue, we extracted the RNA expression profiles of all genes known to code for proteins involved in CSF production. A selection of genes was further investigated with quantitative real-time polymerase chain reaction (qRT-PCR). For selected CSF production proteins, electron microscopic immunogold techniques (EM) and Western blots were performed. Seven genes were expressed in both cysts and controls. The gene encoding the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 was significantly up-regulated in AC. Gene expression data were supported by Western blot. EM demonstrated NKCC1 expressed at the plasma membranes of the cyst-lining cells. This result points at secretion as the main mechanism of cyst filling, and NKCC1 as the key candidate of fluid transport. Based on these findings, we hypothesize that selective NKCC1 inhibitors could be used in preventing expansion of temporal AC.