Loss of astrocyte polarization upon transient focal brain ischemia as a possible mechanism to counteract early edema formation

Steiner, Esther; Enzmann, Gaby U; Lin, Shuo; Ghavampour, Sharang; Hannocks, Melanie-Jane; Zuber, Benoît; Rüegg, Markus A; Sorokin, Lydia; Engelhardt, Britta (2012). Loss of astrocyte polarization upon transient focal brain ischemia as a possible mechanism to counteract early edema formation. GLIA, 60(11), pp. 1646-59. Hoboken, N.J.: Wiley-Blackwell 10.1002/glia.22383

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Brain edema is the main cause of death from brain infarction. The polarized expression of the water channel protein aquaporin-4 (AQP4) on astroglial endfeet surrounding brain microvessels suggests a role in brain water balance. Loss of astrocyte foot process anchoring to the basement membrane (BM) accompanied by the loss of polarized localization of AQP4 to astrocytic endfeet has been shown to be associated with vasogenic/extracellular edema in neuroinflammation. Here, we asked if loss of astrocyte polarity is also observed in cytotoxic/intracellular edema following focal brain ischemia after transient middle cerebral artery occlusion (tMCAO). Upon mild focal brain ischemia, we observed diminished immunostaining for the BM components laminin α4, laminin α2, and the proteoglycan agrin, in the core of the lesion, but not in BMs in the surrounding penumbra. Staining for the astrocyte endfoot anchorage protein β-dystroglycan (DG) was dramatically reduced in both the lesion core and the penumbra, and AQP4 and Kir4.1 showed a loss of polarized localization to astrocytic endfeet. Interestingly, we observed that mice deficient for agrin expression in the brain lack polarized localization of β-DG and AQP4 at astrocytic endfeet and do not develop early cytotoxic/intracellular edema following tMCAO. Taken together, these data indicate that the binding of DG to agrin embedded in the subjacent BM promotes polarized localization of AQP4 to astrocyte endfeet. Reduced DG protein levels and redistribution of AQP4 as observed upon tMCAO might therefore counteract early edema formation and reflect a beneficial mechanism operating in the brain to minimize damage upon ischemia.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy 04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
UniBE Contributor:	Enzmann, Gaby, Zuber, Benoît, Engelhardt, Britta
Subjects:	600 Technology > 610 Medicine & health
ISSN:	0894-1491
Publisher:	Wiley-Blackwell
Language:	English
Submitter:	Benoît Zuber
Date Deposited:	04 Oct 2013 14:39
Last Modified:	05 Dec 2022 14:12
Publisher DOI:	10.1002/glia.22383
PubMed ID:	22782669
Web of Science ID:	000308444000002
URI:	https://boris.unibe.ch/id/eprint/16036 (FactScience: 223586)