Sustained astrocytic clusterin expression improves remodeling after brain ischemia.
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.
Department of Psychiatry, HUG, Belle-Idée, 2, ch. du Petit-Bel-Air, 1225 Chêne-Bourg Geneva Switzerland.
Anouk
A
Imhof
Yves
Y
Charnay
Philippe G
PG
Vallet
Bruce
B
Aronow
Eniko
E
Kovari
Lars E
LE
French
Constantin
C
Bouras
Panteleimon
P
Giannakopoulos
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020520:Brain Infarction / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051152:Clusterin / Q000235:genetics*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D014945:Wound Healing / Q000235:genetics
C495243:Clu protein, mouse; D051152:Clusterin; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger