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

Thomas Tourdias, Nobuyuki Mori, Iulus Dragonu, Nadège Cassagno, Claudine Boiziau, Justine Aussudre, Bruno Brochet, Chrit Moonen, Klaus G Petry, Vincent Dousset
Journal of Neuroinflammation. 2011-01-01; 8(1): 143
DOI: 10.1186/1742-2094-8-143

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1. J Neuroinflammation. 2011 Oct 19;8:143. doi: 10.1186/1742-2094-8-143.

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

Tourdias T(1), Mori N, Dragonu I, Cassagno N, Boiziau C, Aussudre J, Brochet B,
Moonen C, Petry KG, Dousset V.

Author information:
(1)INSERM U,1049 Neuroinflammation, Imagerie et Thérapie de la Sclérose en
Plaques, F-33076 Bordeaux, France.

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
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.

DOI: 10.1186/1742-2094-8-143
PMCID: PMC3220647
PMID: 22011386 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus