Correspondence of AQP4 expression and hypoxic‐ischaemic brain oedema monitored by magnetic resonance imaging in the immature and juvenile rat

Abstract

Whether the water channel protein AQP4 is involved in the very early cell swelling and brain oedema observed with cerebral hypoxia-ischaemia (HI) and whether this response depends on the maturity of brain were investigated by comparing regional changes in AQP4 protein expression and signal intensity on magnetic resonance (MR) images in immature and juvenile brains. Maps of T2 and the apparent diffusion coefficient (ADC) of water were acquired in 1- and 4-week-old rats at times prior to HI, within the last 5 min of HI and 1 h or 24 h afterwards. AQP4 expression assessed with Western blotting was not significantly reduced until 24 h post-HI irrespective of age. However, AQP4 immunostaining was decreased at the end of HI and at 1 h or 24 h after HI in the hemisphere ipsilateral to the occlusion with changes being similar in both age groups and coinciding well with regional reductions in ADC. IgG immunostaining to assess blood-brain barrier integrity and T2 were unchanged at early time points in 4-week old rats despite decreases in AQP4 immunostaining. Thus, at early time points there were decreases in AQP4 detected with immunostaining but not Western blotting methods. However, the good correlation between alterations in ADC and AQP4 immunostaining suggests that changes in the AQP4 are involved in some of the early changes in brain water distribution observed in hypoxia-ischemia, and supports the speculation that AQP4 is involved in the transport of water across the perivascular membranes into the vascular lumen.

Aquaporin‐4 knockdown ameliorates hypoxic‐ischemic cerebral edema in newborn piglets

“…Notably, the changes in AQP4 expression paralleled the changes in edema as demonstrated on MRI (15,18,19). Upregulation of AQP4 may occur during trauma-induced cytotoxic edema in rats, and the outcome becomes worse with the upregulation of AQP4 (8), whereas edema is less severe with the downregulation or knockout of AQP4 during cytotoxic edema (20,21).…”

Glial Cell Aquaporin-4 Overexpression in Transgenic Mice Accelerates Cytotoxic Brain Swelling

“…Up-regulated AQP4 expression was also found in penetrating brain injury in rats (4) and in cortical contusion injury (3). Other studies show reduced AQP4 expression in response to various insults, including transient middle cerebral artery occlusion in rats (20,21) and diffuse (22) and focal (23) head trauma. Notwithstanding some conflicting results in the literature regarding the direction of change in AQP4 expression in various pathologies, it is concluded that brain AQP4 expression is sensitive to many types of insults, which, from the functional data here, translates to altered brain water balance.…”

The Protein Kinase C Activator Phorbol Myristate Acetate Decreases Brain Edema by Aquaporin 4 Downregulation after Middle Cerebral Artery Occlusion in the Rat

“…The specific anatomical and cellular localization of aquaporin 4 (AQP 4) water channels in the central nervous system suggests that this protein plays a crucial role in the cerebral water balance . Recently, the role of AQP4 in maintaining water homeostasis during the development of post-traumatic or ischemic brain edema has been described, although conflicting results have been obtained using different models (Hu et al, 2005;Ke et al, 2001;Kiening et al, 2002;Lu and Sun, 2003;Manley et al, 2000;Meng et al, 2004;Sato et al, 2000;Sun et al, 2003;Taniguchi et al, 2000;Vizuete et al, 1999).…”