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Jian Guo, Xinjiang Mi, Rucai Zhan, Meng Li, Lin Wei, Jinlong Sun
(First Department of Neurosurgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China (mainland))
Med Sci Monit 2018; 24: ANS4204-4212
Aquaporin 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 AND METHODS: The 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.
RESULTS: The 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.
CONCLUSIONS: Our study demonstrates that silencing AQP4 aggravates hydrocephalus, indicating that AQP4 protects against hydrocephalus.