Aquaporins (AQPs) are membrane proteins that facilitate water and small solute movement in tissues. Hydrocephalus is the main central nervous system disorder associated with defective CSF turnover [3, 6]. Aquaporin-4 (AQP4) is a water channel mainly located at the blood–brain barrier (BBB) and is associated with the elimination of cerebral edema via this route . AQP4 levels are significantly altered in kaolin-induced hydrocephalus, suggesting that AQP4 could play an important neurodefensive role in hydrocephalus and CSF disorders [17, 18]. Biphasic AQP1 expression in the choroid plexus with increased AQPs 1 and 4 at the brain-fluid interfaces may indicate compensatory mechanisms to regulate choroidal CSF secretion and increase parenchymal fluid absorption in high-pressure hydrocephalus .
A study  detecting AQP1 and AQP4 in CSF determined that the mean concentration of AQP1 in CSF was significantly higher in patients with bacterial meningitis (BM), AQP4 was also greater but not significantly so . One can see that most of these studies, in hydrocephalus cases, used animal models (AQP4-knockout mice, H-Tx rats, and kaolin and L-α-lysophosphatidylcholine stearoyl-injection models of hydrocephalus), which indicate that there is an up-regulation of AQP4 expression at the BBB interface. Only one study reported sporadic cases of obstructive hydrocephalus in a subgroup of AQP4-knockout mice . But few publications have studied the association between aquaporins and congenital hydrocephalus. Therefore, all existing studies using animal models propose an adaptive and protective role of AQP4 to resolve hydrocephalic edema at the brain barriers in the pathophysiology of hydrocephalus .
Thus, despite their inherent relationship in the processes of water transport in the previously mentioned conditions (edema reabsorption, meningitis, hydrocephalus), AQP4, by means of connexin-43 (Cx43) regulation, is also a modulator of the formation and development of the gap junctions in the ependymal basolateral membrane and astrocyte feet. It has been reported that knockdown and knockout AQP4 mice downregulate the expression of Cx43 in different in vitro studies [10, 21, 22]. Furthermore, AQP4 not only regulates the expression of Cx43, but also secondarily intervenes in the ependyma denudation, given that the decrease of gap junctions, in which Cx43 is the main protein [15, 16].
The CSF protein concentration is compartmental related, thus in the lumbar compartment the protein concentration is higher than in the ventricular compartment . Despite that, in results presented here the AQP4 was increased in the CSF of the hydrocephalus samples taken from the lateral ventricle compared to control CSF taken from lumbar puncture. This increase in CSF AQP4 in hydrocephalus may occur as a consequence of the loss of communication between ependymal cells and subsequent denudation of ependyma, when AQP4 would pass into the CSF. This ependymal loss is accompanied by a microglial and astroglial cell reaction; the subependymal astroglial cells respond by proliferation in such a way that they form a glial scar-like covering of the ventricular surface to replace the ependyma [24, 25]. At that time, if cellular death or disruption occurs, the AQP4 could be in contact with the ventricular lumen and may pass into the CSF. Furthermore, the occurrence of various stages of ependymal denudation within full-term spina bifida aperta (SBA) fetuses, suggests that there may be continuation of the process after birth and that cases of communicating hydrocephalus could soon develop into non-communicating hydrocephalus . Therefore, the increase of CSF AQP4 may be a consequence of the ependymal denudation and the level of AQP4 in the CSF could be an indicator of the ependyma status and the hydrocephalus stage.