Aquaporin-4 gene deletion in mice increases focal edema associated with staphylococcal brain abscess.
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 (approximately 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.
Bloch
Orin
O
Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA.
Papadopoulos
Marios C
MC
Manley
Geoffrey T
GT
Verkman
A S
AS
D000818:Animals; D051401:Aquaporin 4; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000473:pathology; D001834:Body Water / Q000378:metabolism; D001922:Brain Abscess / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017353:Gene Deletion; D005911:Gliosis / Q000473:pathology; D007427:Intracranial Pressure; D051379:Mice; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000150:complications* / Q000378:metabolism* / Q000473:pathology
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D020346:Aquaporins; D018696:Neuroprotective Agents