Abstract
Background
Aquaporin-4 (aqp-4) is a member of water channel family proteins primarily expressed in the central nervous system. Physiologically it is the main channel providing water transport into the nervous system water compartments and across the blood–brain barrier. Several studies demonstrated its compensatory role in severe hydrocephalus. However, its role is not clear during the initial stages of hydrocephalus.
Objective
This study was designed to investigate aqp-4 expression in less severe forms of hydrocephalus and to determine its role in disease progression.
Methods
Twenty-five male Wistar-Hannover rats, were distributed into experimental (n = 20) and control (n = 5) groups. Hydrocephalus was induced in the experimental group by injection of 5 μl 25% kaolin suspension into the cisterna magna. Control animals received an injection of 5 μl normal saline. Eight weeks later, the animals were killed by the perfusion-fixation method. Immunohistochemical and Western blot analysis were performed.
Results
Ventricular dilatations were noted in all experimental animals. Both groups demonstrated positive immunoreactive signals to aqp-4. Immunohistochemically there were no changes in aqp-4 pattern and expression intensity between experimental and control animals. Similarly, Western blot analysis revealed mean aqp-4 values in experimental and control groups as 0.3436 and 0.3917, respectively, and the difference did not reach statistical significance (p > 0.05).
Conclusion
Our results indicate that aqp-4 is not up-regulated during the initial stages of hydrocephalus. This implies that aqp-4 may not play a significant role in hydrocephalus compensation until severe ventricular dilatation occurs.
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Comment
The aim of this experimental study was to investigate the supposed protective role of aqp-4 in hydrocephalus. The question is of scientific interest because of the hypothesized facilitated transependymal water transport and egress through the microvasculature. Such a compensatory mechanism may perhaps start when ventricular dilatation occurs at the late stage of hydrocephalus and aqp-4 possibly will facilitate water passage from the ventricles into the brain parenchyma and then from the brain parenchyma into the systemic circulation. The well-designed study was superbly executed.
The present study fails to support this function and indicates that aqp-4 should not be selected as a target for molecular treatment of hydrocephalus. This information should be propagated in the scientific community to avoid supplementary research studies.
Alex Alfieri
Halle-Wittenberg, Germany
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Aghayev, K., Bal, E., Rahimli, T. et al. Aquaporin-4 expression is not elevated in mild hydrocephalus. Acta Neurochir 154, 753–759 (2012). https://doi.org/10.1007/s00701-011-1241-9
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DOI: https://doi.org/10.1007/s00701-011-1241-9