Differential aquaporin 4 expression during edema build-up and resolution phases of brain inflammation

Journal of Neuroinflammation

Vincent Dousset¹  Klaus G Petry³  Chrit Moonen²  Bruno Brochet³  Justine Aussudre³  Claudine Boiziau³  Nadège Cassagno³  Iulus Dragonu²  Nobuyuki Mori³  Thomas Tourdias¹ 

[1] CHU de Bordeaux, Service de Neuroimagerie Diagnostique et Thérapeutique, F-33076 Bordeaux, France;CNRS, UMR 5231 Laboratoire d'Imagerie Moléculaire et Fonctionnelle, F-33076 Bordeaux, France;INSERM U.1049 Neuroinflammation, Imagerie et Thérapie de la Sclérose en Plaques, F-33076 Bordeaux, France

关键词: Magnetic resonance imaging;    Inflammation;    Brain edema;    Blood brain barrier;    Aquaporin 4;   

Others  :  1213050
DOI  :  10.1186/1742-2094-8-143

 received in 2011-06-09, accepted in 2011-10-19,  发布年份 2011

【 摘 要 】

Background

Vasogenic edema dynamically accumulates in many brain disorders associated with brain inflammation, with the critical step of edema exacerbation feared in patient care. Water entrance through blood-brain barrier (BBB) opening is thought to have a role in edema formation. Nevertheless, the mechanisms of edema resolution remain poorly understood. Because the water channel aquaporin 4 (AQP4) provides an important route for vasogenic edema resolution, we studied the time course of AQP4 expression to better understand its potential effect in countering the exacerbation of vasogenic edema.

Methods

Focal inflammation was induced in the rat brain by a lysolecithin injection and was evaluated at 1, 3, 7, 14 and 20 days using a combination of in vivo MRI with apparent diffusion coefficient (ADC) measurements used as a marker of water content, and molecular and histological approaches for the quantification of AQP4 expression. Markers of active inflammation (macrophages, BBB permeability, and interleukin-1β) and markers of scarring (gliosis) were also quantified.

Results

This animal model of brain inflammation demonstrated two phases of edema development: an initial edema build-up phase during active inflammation that peaked after 3 days (ADC increase) was followed by an edema resolution phase that lasted from 7 to 20 days post injection (ADC decrease) and was accompanied by glial scar formation. A moderate upregulation in AQP4 was observed during the build-up phase, but a much stronger transcriptional and translational level of AQP4 expression was observed during the secondary edema resolution phase.

Conclusions

We conclude that a time lag in AQP4 expression occurs such that the more significant upregulation was achieved only after a delay period. This change in AQP4 expression appears to act as an important determinant in the exacerbation of edema, considering that AQP4 expression is insufficient to counter the water influx during the build-up phase, while the second more pronounced but delayed upregulation is involved in the resolution phase. A better pathophysiological understanding of edema exacerbation, which is observed in many clinical situations, is crucial in pursuing new therapeutic strategies.

【 授权许可】

   
2011 Tourdias et al; licensee BioMed Central Ltd.

【 图 表 】

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