Skip to main content Skip to main navigation menu Skip to site footer

The relationship between AQP1 expression in the subventricular zone and severity of hydrocephalus in Rattus Norvegicus strain Sprague-Dawley rats

  • Januarman ,
  • Muhammad Arifin Parenrengi ,
  • Wihasto Suryaningtyas ,
  • Budi Utomo ,
  • Abdul Hafid Bajamal ,
  • Eko Agus Subagio ,


Link of Video Abstract:


Background: Hydrocephalus is a condition of dilation of the ventricles caused by disturbances production, distribution, or absorption of cerebrospinal fluid (CSF). One of the integral membrane proteins identified in facilitating water transport across the plasma membrane is aquaporin-1 (AQP1), which is frequently found in the plexus choroid. However, theoretically also transports water to the subventricular zone (SVZ) with an unknown mechanism. AQP1 expression will be raised in SVZ under hydrocephalus conditions. This study aims to evaluate the relationship between the severity of hydrocephalus and AQP1 levels in SVZ.

Methods: This research was conducted in an experimental design using Rattus Norvegicus rats of the Sprague-Dawley strain, which were injected with kaolin to create a hydrocephalus model. The study included 24 rats, divided into four groups of six each: the control group and the hydrocephalus induction group on day 7, day 14, and day 21. AQP1 expression was observed using immunohistochemical staining and counted semi-quantitatively.

Results: The average AQP1 expression increased with observation time in the rat model in each group. The ANOVA test showed a significant difference between the four study groups (p=0.001). The correlation showed a statistically significant difference (p=0.000). The results showed an increased expression of the SVZ with a higher severity of hydrocephalus.

Conclusion: The severity of hydrocephalus and AQP1 levels in SVZ are correlated, with the latter being higher, the more severe the degree of hydrocephalus.


  1. Rekate HL. The definition and classification of hydrocephalus: a personal recommendation to stimulate debate. Cerebrospinal fluid research. 2008;5(1):1-7.
  2. Winn HR. Youmans and Winn Neurological Surgery E-Book: 4-Volume Set. Elsevier Health Sciences: USA . 2022.
  3. Greenberg MS. Handbook of Neurosurgery. Georg Thieme Verlag: Thieme. 2019.
  4. Dewan MC, Rattani A, Mekary R, Glancz LJ, Yunusa I, Baticulon RE, et al. Global hydrocephalus epidemiology and incidence: systematic review and meta-analysis. Journal of neurosurgery. 2018;130(4):1065-1079.
  5. Melo JRT, de Melo EN, de Vasconcellos ÂG, Pacheco P. Congenital hydrocephalus in the northeast of Brazil: epidemiological aspects, prenatal diagnosis, and treatment. Child's Nervous System. 2013;29(1):1899-1903.
  6. Beitz E, Becker D, von Bülow J, Conrad C, Fricke N, Geadkaew A, et al. In vitro analysis and modification of aquaporin pore selectivity. Aquaporins. 2009;1(1):77-92.
  7. Verkman AS. More than just water channels: unexpected cellular roles of aquaporins. Journal of Cell Science. 2005;118(15):3225-3232.
  8. Owler BK, Pitham T, Wang D. Aquaporins: relevance to cerebrospinal fluid physiology and therapeutic potential in hydrocephalus. Cerebrospinal fluid research. 2010;7(1):1-12.
  9. Longatti PL, Basaldella L, Orvieto E, Fiorindi A, Carteri A. Choroid plexus and aquaporin-1: a novel explanation of cerebrospinal fluid production. Pediatric Neurosurgery. 2004;40(6):277-283.
  10. Olopade FE, Shokunbi MT, Sirén AL. The relationship between ventricular dilatation, neuropathological and neurobehavioural changes in hydrocephalic rats. Fluids and Barriers of the CNS. 2012;9(1):1-10.
  11. Bloch O, Auguste KI, Manley GT, Verkman AS. Accelerated progression of kaolin-induced hydrocephalus in aquaporin-4-deficient mice. Journal of Cerebral Blood Flow & Metabolism. 2006;26(12):1527-1537.
  12. Bakhtiar Y, Sartika D, Muttaqin Z, Arifin MT, Imawati S, Ningrum FH. Trigone point as an alternative location for ventricular shunt insertion. Bali Medical Journal. 2023;12(2):2142–2147.
  13. Kalani MYS, Filippidis AS, Rekate HL. Hydrocephalus and aquaporins: the role of aquaporin-1. In Hydrocephalus: Selected Papers from the International Workshop in Crete Springer Vienna. 2012;1(1):51-54.
  14. Nguyen T, Toussaint J, Xue Y, Raval C, Cancel L, Russell S, et al. Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium. American Journal of Physiology-Heart and Circulatory Physiology. 2015;308(9):H1051-H1064.
  15. Di Curzio DL. Animal models of hydrocephalus. Open Journal of Modern Neurosurgery. 2017;8(1):57-71.
  16. Desai B, Hsu Y, Schneller B, Hobbs JG, Mehta AI, Linninger A. Hydrocephalus: the role of cerebral aquaporin-4 channels and computational modeling considerations of cerebrospinal fluid. Neurosurgical Focus. 2016;41(3):E8.
  17. Jeon T, Park KS, Park SH, Hwang JH, Hwang SK. Expression of aquaporin 1 and 4 in the choroid plexus and brain parenchyma of kaolin-induced hydrocephalic rats. Korean Journal of Neurotrauma. 2017;13(2):68-75.
  18. Hashimoto Y, Matsushige T, Shimonaga K, Hosogai M, Kaneko M, Ono C, et al. Vessel wall imaging predicts the presence of atherosclerotic lesions in unruptured intracranial aneurysms. World Neurosurgery. 2019;132:e775-e782.
  19. Suryaningtyas W, Arifin M, Rantam FA, Bajamal AH, Dahlan YP, Ugrasena IDG, et al. Erythropoietin protects the subventricular zone and inhibits reactive astrogliosis in kaolin-induced hydrocephalic rats. Child's Nervous System. 2019;35(1):469-476.
  20. Trillo-Contreras JL, Ramírez-Lorca R, Villadiego J, Echevarría M. Cellular distribution of brain aquaporins and their contribution to cerebrospinal fluid homeostasis and hydrocephalus. Biomolecules. 2022;12(4):530.
  21. Wang D, Nykanen M, Yang N, Winlaw D, North K, Verkman AS, et al. Altered cellular localization of aquaporin-1 in experimental hydrocephalus in mice and reduced ventriculomegaly in aquaporin-1 deficiency. Molecular and Cellular Neuroscience. 2011;46(1):318-324.
  22. Long CY, Huang GQ, Du Q, Zhou LQ, Zhou JH. The dynamic expression of aquaporins 1 and 4 in rats with hydrocephalus induced by subarachnoid hemorrhage. Folia Neuropathologica. 2019;57(2):182-195.
  23. Mccoy E, Sontheimer H. MAPK induces AQP1 expression in astrocytes following injury. Glia. 2010;58(2):209-217.
  24. Paul L, Madan M, Rammling M, Chigurupati S, Chan SL, Pattisapu JV. Expression of aquaporin 1 and 4 in a congenital hydrocephalus rat model. Neurosurgery. 2011;68(2):462-473.
  25. Castañeyra-Ruiz L, González-Marrero I, González-Toledo JM, Castañeyra-Ruiz A, de Paz-Carmona H, Castañeyra-Perdomo A, et al. Aquaporin-4 expression in the cerebrospinal fluid in congenital human hydrocephalus. Fluids and Barriers of the CNS. 2013;10(1):1-5.
  26. González-Marrero I, Hernández-Abad LG, González-Gómez M, Soto-Viera M, Carmona-Calero EM, Castañeyra-Ruiz L, et al. Altered Expression of AQP1 and AQP4 in Brain Barriers and Cerebrospinal Fluid May Affect Cerebral Water Balance during Chronic Hypertension. International Journal of Molecular Sciences. 2022;23(20):12277.
  27. Golden N, Mardhika PE, Niryana W, Sukarya IM, Prabawa IPY. Risk factors and novel prognostic score for predicting the 14-day mortality of severe traumatic brain injury patients. Intisari Sains Medis. 2020;11(3):1020-1028.
  28. Arifin MT, Purnomo F, Muttaqin Z, Bakhtiar Y, Andar E, Priambada D, et al. Cerebrospinal fluid contents and risk of shunt exposure in hydrocephalus. Bali Medical Journal. 2019;8(3):841–843.
  29. Mao X, Enno TL, Del Bigio MR. Aquaporin 4 changes in rat brain with severe hydrocephalus. European Journal of Neuroscience. 2006;23(11):2929-2936.
  30. Ruspanah I, Hermanto Y, Taihuttu YMJ, Ruspanah A, Adam A, Imron A. Implications of VP-Shunt, Sodium Level, Glucose Level Ratio and Neurologic Deficit as Clinical Outcome Prognostic Factor in Adult Meningitis Tuberculosis with Acute Hydrocephalus in Dr. Hasan Sadikin General Hospital. Bali Medical Journal. 2022;11(2):715–719.

How to Cite

Januarman, Parenrengi, M. A., Suryaningtyas, W., Utomo, B., Bajamal, A. H., & Subagio, E. A. (2023). The relationship between AQP1 expression in the subventricular zone and severity of hydrocephalus in Rattus Norvegicus strain Sprague-Dawley rats. Bali Medical Journal, 12(3), 2401–2406.




Search Panel

Google Scholar
BMJ Journal

Muhammad Arifin Parenrengi
Google Scholar
BMJ Journal

Wihasto Suryaningtyas
Google Scholar
BMJ Journal

Budi Utomo
Google Scholar
BMJ Journal

Abdul Hafid Bajamal
Google Scholar
BMJ Journal

Eko Agus Subagio
Google Scholar
BMJ Journal