Aquaporin-4 gene deletion in mice increases focal edema associated with staphylococcal brain abscess

Orin Bloch, Marios C. Papadopoulos, Geoffrey T. Manley, A. S. Verkman

Research output: Contribution to journalArticle

139 Scopus citations

Abstract

Brain abscess is associated with local vasogenic edema, which leads to increased intracranial pressure and significant morbidity. Aquaporin-4 (AQP4) is a water channel expressed in astroglia at the blood-brain and brain-CSF barriers. To investigate the role of AQP4 in brain abscess-associated edema, live Staphylococcus aureus (105 colony-forming units) was injected into the striatum to create a focal abscess. Wild-type and AQP4-deficient mice had comparable immune responses as measured by brain abscess volume (∼ 3.7 mm3 at 3 days), bacterial count and cytokine levels in brain homogenates. Blood-brain barrier permeability was increased comparably in both groups as assessed by extravasation of Evans blue dye. However, at 3 days the AQP4 null mice had significantly higher intracranial pressure (mean ± SEM 27 ± 2 vs. 17 ± 2 mmHg; p < 0.001) and brain water content (81.0 ± 0.3 vs. 79.3 ± 0.5% water by weight in the abscess-containing hemisphere; p < 0.01) than wild-type mice. Reactive astrogliosis was found throughout the abscess-containing hemisphere; however, only a subset of astrocytes in the peri-abscess region of wild-type mice had increased AQP4 immunoreactivity. Our findings demonstrate a protective effect of AQP4 on brain swelling in bacterial abscess, suggesting that AQP4 induction may reduce vasogenic edema associated with cerebral infection.

Original languageEnglish (US)
Pages (from-to)254-262
Number of pages9
JournalJournal of Neurochemistry
Volume95
Issue number1
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

Keywords

  • Aquaporin-4
  • Cerebral edema
  • Intracranial pressure
  • Vasogenic edema
  • Water channel

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Aquaporin-4 gene deletion in mice increases focal edema associated with staphylococcal brain abscess'. Together they form a unique fingerprint.

Cite this