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

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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.