Sustained astrocytic clusterin expression improves remodeling after brain ischemia

Neurobiol Dis. 2006 May;22(2):274-83. doi: 10.1016/j.nbd.2005.11.009. Epub 2006 Feb 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Brain / metabolism*
  • Brain / pathology
  • Brain / physiopathology
  • Brain Infarction / genetics
  • Brain Infarction / metabolism
  • Brain Infarction / physiopathology
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism*
  • Brain Ischemia / physiopathology
  • Clusterin / genetics*
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosis / genetics
  • Gliosis / metabolism
  • Gliosis / physiopathology
  • Infarction, Middle Cerebral Artery / genetics
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Plasticity / genetics*
  • RNA, Messenger / metabolism
  • Up-Regulation / genetics
  • Wound Healing / genetics


  • Clu protein, mouse
  • Clusterin
  • Glial Fibrillary Acidic Protein
  • RNA, Messenger