Brain Water Mobility Decreases after Astrocytic Aquaporin-4 Inhibition Using RNA Interference
Open Access
- 29 September 2010
- journal article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 31 (3), 819-831
- https://doi.org/10.1038/jcbfm.2010.163
Abstract
Neuroimaging with diffusion-weighted imaging is routinely used for clinical diagnosis/prognosis. Its quantitative parameter, the apparent diffusion coefficient (ADC), is thought to reflect water mobility in brain tissues. After injury, reduced ADC values are thought to be secondary to decreases in the extracellular space caused by cell swelling. However, the physiological mechanisms associated with such changes remain uncertain. Aquaporins (AQPs) facilitate water diffusion through the plasma membrane and provide a unique opportunity to examine the molecular mechanisms underlying water mobility. Because of this critical role and the recognition that brain AQP4 is distributed within astrocytic cell membranes, we hypothesized that AQP4 contributes to the regulation of water diffusion and variations in its expression would alter ADC values in normal brain. Using RNA interference in the rodent brain, we acutely knocked down AQP4 expression and observed that a 27% AQP4-specific silencing induced a 50% decrease in ADC values, without modification of tissue histology. Our results demonstrate that ADC values in normal brain are modulated by astrocytic AQP4. These findings have major clinical relevance as they suggest that imaging changes seen in acute neurologic disorders such as stroke and trauma are in part due to changes in tissue AQP4 levels.Keywords
This publication has 33 references indexed in Scilit:
- Greatly impaired migration of implanted aquaporin‐4‐deficient astroglial cells in mouse brain toward a site of injuryThe FASEB Journal, 2006
- Time course of aquaporin expression after transient focal cerebral ischemia in miceJournal of Neuroscience Research, 2006
- Involvement of aquaporin-4 in astroglial cell migration and glial scar formationJournal of Cell Science, 2005
- New possible roles for aquaporin‐4 in astrocytes: cell cytoskeleton and functional relationship with connexin43The FASEB Journal, 2005
- Hypoxia/hypoglycemia preconditioning prevents the loss of functional electrical activity in organotypic slice culturesBrain Research, 2005
- Quantitative morphological study of microglial cells in the ischemic rat brain using principal component analysisJournal of Neuroscience Methods, 2005
- In VivoMeasurement of Brain Extracellular Space Diffusion by Cortical Surface PhotobleachingJournal of Neuroscience, 2004
- D-JNKI1, a Cell-Penetrating c-Jun-N-Terminal Kinase Inhibitor, Protects Against Cell Death in Severe Cerebral IschemiaStroke, 2004
- Correspondence of AQP4 expression and hypoxic‐ischaemic brain oedema monitored by magnetic resonance imaging in the immature and juvenile ratEuropean Journal of Neuroscience, 2004
- New insights into water transport and edema in the central nervous system from phenotype analysis of aquaporin-4 null miceNeuroscience, 2004