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Aquaporin‐4 gene deletion in mice increases focal edema associated with staphylococcal brain abscess
Author(s) -
Bloch Orin,
Papadopoulos Marios C.,
Manley Geoffrey T.,
Verkman A. S.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03362.x
Subject(s) - evans blue , brain abscess , abscess , pathology , extravasation , edema , medicine , blood–brain barrier , aquaporin 4 , cerebral edema , midline shift , anesthesia , central nervous system , surgery , computed tomography
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 (10 5 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 mm 3 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.