Abstract TP452: Systemic Inflammation Reverses Stroke-induced Changes in Astrocytic Aquaporin-4 Expression
Introduction: Aquaporin-4 (AQP4) is a perivascular water channel that plays a key role in regulating the blood-brain barrier (BBB). Stroke acutely reduces expression and polarization of AQP4 on astrocytic endfeet, and these vascular changes might persist chronically and evolve with systemic inflammation. Reduced polarization of AQP4 after traumatic brain injury (TBI) leads to impaired perivascular clearance of debris and cognitive decline in mice, and if similar changes occur after stroke, then they may also contribute to post-stroke dementia.
Hypothesis: Stroke will cause lasting changes in vascular organization, reducing astrocytic AQP4 expression and polarization in the area of injury.
Methods: Thirty male Balb/cJ mice were subjected to distal middle cerebral artery ligation, allowed to survive for 28 days, and sacrificed 24 hours after injection with lipopolysaccharide (LPS, 0.33 mg/kg i.p.) or saline to model systemic inflammation. Three sequential coronal sections (20 μm) near the site of infarct (0.25 mm from Bregma) were stained with lectin, AQP4, and glial fibrillary acidic protein (GFAP) to evaluate BBB organization. Vessel density was evaluated with AngioTool. AQP4 expression was evaluated by Western blot.
Results: Stroke increased vascular density in the injured hemisphere (11 ± 0.8% vs 7.6 ± 0.8% in sham mice, p < 0.05). Decreased AQP4 expression and polarization near the site of the infarct was observed, which were reversed with LPS (Figure 1). LPS increased AQP4 protein levels in stroke (2.5 ± 0.37 fold-increase, p < 0.05), but not sham mice.
Conclusions: Stroke caused a chronic increase in vascular density, with peri-infarct vessels displaying decreased expression and changed polarity of AQP4. However, with systemic inflammation, this is reversed, potentially contributing to neuroinflammation and worsened cognitive outcomes in stroke patients who encounter infections via increased permeability of these abnormal vessels.
Author Disclosures: Y. Sun: None. M.D. Howe: None. M. Spychala: None. R. Rosow: None. L.D. McCullough: Other; Modest; Speaker for Genentech.
- © 2016 by American Heart Association, Inc.