Mildly Reduced Brain Swelling and Improved Neurological Outcome in Aquaporin-4 Knockout Mice following Controlled Cortical Impact Brain Injury
- 1 October 2015
- journal article
- Published by Mary Ann Liebert Inc in Journal of Neurotrauma
- Vol. 32 (19), 1458-1464
- https://doi.org/10.1089/neu.2014.3675
Abstract
Brain edema following traumatic brain injury (TBI) is associated with considerable morbidity and mortality. Prior indirect evidence has suggested the involvement of astrocyte water channel aquaporin-4 (AQP4) in the pathogenesis of TBI. Here, focal TBI was produced in wild type (AQP4(+/+)) and knockout (AQP4(-/-)) mice by controlled cortical impact injury (CCI) following craniotomy with dura intact (parameters: velocity 4.5 m/sec, depth 1.7 mm, dwell time 150 msec). AQP4-deficient mice showed a small but significant reduction in injury volume in the first week after CCI, with a small improvement in neurological outcome. Mechanistic studies showed reduced intracranial pressure at 6 h after CCI in AQP4(-/-) mice, compared with AQP4(+/+) control mice (11 vs. 19 mm Hg), with reduced local brain water accumulation as assessed gravimetrically. Transmission electron microscopy showed reduced astrocyte foot-process area in AQP4(-/-) mice at 24 h after CCI, with greater capillary lumen area. Blood-brain barrier disruption assessed by Evans blue dye extravasation was similar in AQP4(+/+) and AQP4(-/-) mice. We conclude that the mildly improved outcome in AQP4(-/-) mice following CCI results from reduced cytotoxic brain water accumulation, though concurrent cytotoxic and vasogenic mechanisms in TBI make the differences small compared to those seen in disorders where cytotoxic edema predominates.Keywords
This publication has 44 references indexed in Scilit:
- ‘Hit & Run’ Model of Closed-Skull Traumatic Brain Injury (TBI) Reveals Complex Patterns of Post-Traumatic AQP4 DysregulationJournal of Cerebral Blood Flow & Metabolism, 2013
- Microstructural Basis of Contusion Expansion in Traumatic Brain Injury: Insights from Diffusion Tensor ImagingJournal of Cerebral Blood Flow & Metabolism, 2013
- Valproate Administered after Traumatic Brain Injury Provides Neuroprotection and Improves Cognitive Function in RatsPLOS ONE, 2010
- Effect of Secondary Insults upon Aquaporin-4 Water Channels following Experimental Cortical Contusion in RatsJournal of Neurotrauma, 2010
- Amyloid precursor protein secretases as therapeutic targets for traumatic brain injuryNature Medicine, 2009
- Uniquely Hominid Features of Adult Human AstrocytesJournal of Neuroscience, 2009
- Role of Aquaporin-4 in Cerebral Edema and StrokeHandbook of Experimental Pharmacology, 2008
- Aquaporin‐4 facilitates reabsorption of excess fluid in vasogenic brain edemaThe FASEB Journal, 2004
- Neuroprotective Effect of SolCD39, a Novel Platelet Aggregation Inhibitor, on Transient Middle Cerebral Artery Occlusion in RatsStroke, 2003
- Diffusion-weighted imaging differentiates ischemic tissue from traumatized tissue.Stroke, 1994