Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperFluid-percussion brain injury induces changes in aquaporin channel expression
Highlights
▶Fluid-percussion brain injury induces increases in aquaporin 1 and 9. ▶Levels of aquaporins 3 and 4 are decreased after fluid-percussion brain injury. ▶An inhibitor of aquaporin 1 and 4 increases water content in the non-injured brain. ▶Aquaporin 1 and 4 inhibition does not reduce edema after fluid-percussion brain injury.
Section snippets
Fluid-percussion brain injury model
The experiments were carried out using 99 adult male Sprague Dawley rats (300–400 g, Charles Rivers Laboratories, Wilmington, MA, USA). All experimental procedures were in compliance with the National Institute of Health Guide for the Care and Use of Laboratory Animals and approved by the University of Miami Institutional Animal Care and Use Committee. Animals were anesthetized with 3% isoflurane, 70% N2O, and 30% O2. The animals received a 4.8 mm craniotomy (3.8 mm posterior to bregma, 2.5 mm
Results
AQP4 has been shown to be highly regulated in several experimental brain injury models (Ke et al., 2001, Kiening et al., 2002, Sun et al., 2003, Zhao et al., 2005, Guo et al., 2006, Taya et al., 2008, Ding et al., 2009, Higashida et al., 2011). However, whether other AQPs are regulated after moderate parasagittal FPI is still unknown. In the uninjured brain, AQP1 expression is restricted to the choroid plexus (Speake et al., 2003). To determine if this expression pattern changes after injury,
Discussion
Understanding the changes that occur after brain injury in molecules that subserve water transport may yield novel therapeutic targets for the treatment of edema. To this end, we analyzed the brain for changes in the water channels AQP1, 3, 4, and 9 after moderate parasagittal FPI. We observed that AQP1 and 9 significantly increased in the ipsilateral parietal cortex after injury, whereas AQP3 and 4 were unchanged except for a slight decrease at 7 days post-injury. These changes in protein were
Conclusion
In summary, our data demonstrate that after moderate parasagittal FPI, levels of AQP1 and 9, but not AQP3 or 4, significantly increase from 30 min to 24 h post-injury. Pharmacological inhibition of AQP1 and 4 with a novel drug increased water content in the non-injured brain, and did not reduce edema induced by TBI. These studies suggest that AQP9 is a potential therapeutic target to reduce edema and prevent the devastating consequences of edema after TBI, and that antagonists of AQP water
Acknowledgments
This work was supported by The Miami Project to Cure Paralysis, The Buoniconti Fund to Cure Paralysis, and the Channel 7 Children's Research Foundation, Australia. We thank Dr. C. Falo for scientific input, Dr. G. Flynn for providing AqB013, and Drs. Helen Bramlett and Michael Norenberg for critical reading of the manuscript.
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