The dynamic expression of aquaporins 1 and 4 in rats with hydrocephalus induced by subarachnoid haemorrhage

Folia Neuropathol. 2019;57(2):182-195. doi: 10.5114/fn.2019.86296.

Abstract

Introduction: Hydrocephalus is a common complication of subarachnoid haemorrhage (SAH). As transmembrane water channels, aquaporins 1 and 4 (AQP1 and AQP4) are involved in the pathogenesis of hydrocephalus. We aimed to assess the association between the expressions of AQP1 and AQP4 and the severity and duration of hydrocephalus after SAH.

Material and methods: A double haemorrhage model by injection of autologous blood into the cisterna magna was used to induce SAH in rats. Sham rats received the same procedures, but with the injection of normal saline. The SAH group was divided into the SAH with hydrocephalus group and SAH without hydrocephalus group after identifying hydrocephalus histologically. AQP1 and AQP4 in ventricle regions were detected by immunofluorescence, quantitative polymerase chain reaction (qPCR) and western blot.

Results: Hydrocephalus was the most severe at day 3 after SAH. AQP1 and AQP4 mRNA and protein levels increased at day 1 and peaked at day 3. The SAH with hydrocephalus group had a higher expression of AQP1 and AQP4 than the SAH without hydrocephalus group. Higher AQP1 levels were found at the apical and basolateral membrane of the choroid plexus epithelium, while higher AQP4 levels were found in the ependymal cells. A positive correlation between the relative lateral ventricle area and the ratio of AQP1/AQP4 proteins was identified.

Conclusions: AQP1 and AQP4 are remarkably correlated with the severity of hydrocephalus induced by SAH. AQP1 and AQP4 are potential drug targets for developing therapeutic strategies against hydrocephalus.

Keywords: aquaporin-1; aquaporin-4; hydrocephalus; subarachnoid haemorrhage.

MeSH terms

  • Animals
  • Aquaporin 1 / metabolism*
  • Aquaporin 4 / metabolism*
  • Brain / metabolism*
  • Disease Models, Animal
  • Hydrocephalus / etiology
  • Hydrocephalus / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / metabolism*

Substances

  • Aquaporin 4
  • Aquaporin 1