Sustained astrocytic clusterin expression improves remodeling after brain ischemia

Abstract

Clusterin is a glycoprotein highly expressed in response to tissue injury. Using clusterin-deficient (Clu−/−) mice, we investigated the role of clusterin after permanent middle cerebral artery occlusion (MCAO). In wild-type (WT) mice, clusterin mRNA displayed a sustained increase in the peri-infarct area from 14 to 30 days post-MCAO. Clusterin transcript was still present up to 90 days post-ischemia in astrocytes surrounding the core infarct. Western blot analysis also revealed an increase of clusterin in the ischemic hemisphere of WT mice, which culminates up to 30 days post-MCAO. Concomitantly, a worse structural restoration and higher number of GFAP-reactive astrocytes in the vicinity of the infarct scar were observed in Clu−/− as compared to WT mice. These findings go beyond previous data supporting a neuroprotective role of clusterin in early ischemic events in that they demonstrate that this glycoprotein plays a central role in the remodeling of ischemic damage.

Keywords

• Astrocytes
• Apolipoprotein J
• Clusterin-deficient mice
• Middle cerebral artery occlusion
• Neuroprotective effect