Aquaporin 4 Silencing Aggravates Hydrocephalus Induced by Injection of Autologous Blood in Rats

Abstract

BackgroundAquaporin 4 (AQP4), the most abundant aquaporin in the brain, is a type of bidirectional water channel controlling the brain-water balance and plays a critical role in physiologic and pathologic water balance in the brain. AQP4 was reported to be elevated in hydrocephalus; therefore, we hypothesized that AQP4 contributes to hydrocephalus. In this study, the role of AQP4 in hydrocephalus was explored.Material/MethodsThe hydrocephalus rat model was established by injection of autologous blood. On Day 1 and Day 3 after injection of autologous blood, magnetic resonance imaging (MRI) and hematoxylin-eosin (HE) staining were performed to detect the changes in ventricles, and quantitative real-time PCR (qRT-PCR) and immunohistochemistry were carried out to detect the changes in AQP4 level. Thereafter, an AQP4-specific siRNA was used to downregulate AQP4. Then, on Day 3 after injection of autologous blood, the levels of AQP4 and connexin-43 were detected by qRT-PCR, immunohistochemistry, immunofluorescence, or Western blot analysis. MRI and HE staining were performed to detect the changes in ventricles, and Evans blue extravasation assay was used to assess blood-brain barrier integrity.ResultsThe hydrocephalus rat model was established successfully, and hydrocephalus rats showed a higher AQP4 level. Silencing AQP4 aggravated the hydrocephalus, with enlarged lateral ventricles and destruction of ependymal integrity and blood-brain barrier.ConclusionsOur study demonstrates that silencing AQP4 aggravates hydrocephalus, indicating that AQP4 protects against hydrocephalus.

Poldip2 mediates blood‐brain barrier disruption and cerebral edema by inducing AQP4 polarity loss in mouse bacterial meningitis model

“…AQP4 is abundantly expressed in astrocytic endfeet processes in direct contact with blood vessels 7‐9 . The specific highly polarized expression of AQP4 was suggested to play critical roles in maintaining cerebral water balance and BBB integrity 10‐13 . Previous studies have reported that AQP4 polarity was disturbed in various neurological diseases that cause brain edema and BBB disruption 14‐17 .…”

Altered Expression of AQP1 and AQP4 in Brain Barriers and Cerebrospinal Fluid May Affect Cerebral Water Balance during Chronic Hypertension

“…Our previous results have demonstrated the presence of AQP1 and AQP4 in CSF when studying different pathologies [ 26 , 27 , 34 , 46 ]. In the present study, we quantified AQP1 and AQP4 by ELISA and Western blot.…”

“…Brain-derived extracellular vesicles (EVs) have been identified in CSF and blood in both healthy and pathophysiological conditions [ 47 ]. It has been proposed that the presence of AQPs in CSF may be due to their secretion by EVs [ 26 , 27 , 46 , 48 , 49 ]. Our group has reported the expression of AQP4 in the EVs released into the ventricular system associated with ventricular zone glial activation [ 46 ].…”

“…Changes in CSF homeostasis have been heavily associated with the pathophysiology of hydrocephalus [ 22 , 23 ]. Alterations in AQPs expression may contribute to hydrocephalus due to impaired water reabsorption in the venous compartment [ 24 , 25 , 26 ]. Previous reports showed that the ventricular system anatomy and associated CSF transport pattern differed between SHR and WKY rats due to hydrocephalus in SHRs, cerebroventricular volumes are larger and brain volumes significantly smaller in SHR compared to WKY rats [ 27 ].…”

Aquaporine 4 Expression on End Feet Astrocyte Before and After Cerebrospinal Fluid Drainage of Hydrocephalus Mice Model

“…13 AQP4 functions in the physiology of water movement in the brain. 16 AQP4 facilitates water accumulation in cytotoxic edema and excess water clearance in the brain in vasogenic and interstitial edema. 17 In acute hydrocephalus.…”