Effects of Aquaporin-4 on edema formation following intracerebral hemorrhage

Exp Neurol. 2010 Jun;223(2):485-95. doi: 10.1016/j.expneurol.2010.01.015. Epub 2010 Feb 2.


Objective: Intracerebral hemorrhage (ICH) constitutes 10% to 15% of all strokes and is associated with high morbidity and mortality. To date, little is known about the role of AQP4 (Aquaporin-4), which is abundantly expressed in pericapillary astrocyte foot processes and in edema formation after intracerebral hemorrhage. The purpose of this study was to examine the role of AQP4 in edema formation after ICH by using AQP4(-/-) mice.

Methods: ICH was induced by microinjecting 5microl autologous whole blood into the striatum of AQP4(+/+) and AQP4(-/-) mice. We compared neurological deficits, brain edema contents of whole hemorrhagic ipsilateral hemisphere, specific gravity of brain tissue surrounding hematoma, Evans blue leakage and ultrastructure of brain microvessels between AQP4(+/+) and AQP4(-/-) mice following ICH. Histological changes were also detected with Nissl's staining and TUNEL staining.

Results: Our experiments showed a significant increase of AQP4 expression following ICH in AQP4(+/+) mice. AQP4 deletion aggravated neurological deficits and brain edema contents of whole hemorrhagic ipsilateral hemisphere. Besides, it also reduced the specific gravity of brain tissue surrounding hematoma. Moreover, it enhanced Evans blue leakage and ultrastructure of brain microvessel damage. Histology also showed less Nissl's staining and more TUNEL staining in AQP4(-/-) mice following ICH.

Conclusions: These results suggest that AQP4 deletion increases ICH damage, including edema formation, blood-brain barrier damage and neuronal death/TUNEL-positive cells. Further studies on the protective role of activated AQP4 expression following ICH may provide useful therapeutic target for ICH-induced brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 4 / genetics*
  • Aquaporin 4 / metabolism*
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Blood-Brain Barrier / ultrastructure
  • Brain Edema / metabolism*
  • Brain Edema / pathology*
  • Cell Death
  • Cerebral Hemorrhage / metabolism*
  • Cerebral Hemorrhage / pathology*
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Fluorescent Antibody Technique
  • In Situ Nick-End Labeling
  • Male
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Specific Gravity
  • Stroke / metabolism
  • Stroke / pathology
  • Tight Junctions / metabolism
  • Tight Junctions / pathology
  • Tight Junctions / ultrastructure
  • Water / metabolism


  • Aqp4 protein, mouse
  • Aquaporin 4
  • Water