CNS wound healing is severely depressed in metallothionein I- and II- deficient mice

Milena Penkowa, Javier Carrasco, Mercedes Giralt, Torben Moos, Juan Hidalgo*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

141 Citations (Scopus)


To characterize the physiological role of metallothioneins I and II (MT- I+II) in the brain, we have examined the chronological effects of a freeze injury to the cortex in normal and MT-I+II null mice. In normal mice, microglia/macrophage activation and astrocytosis were observed in the areas surrounding the lesion site, peaking at ~1 and 3 d postlesion (dpl), respectively. At 20 dpl, the parenchyma had regenerated. Both brain macro phages and astrocytes surrounding the lesion increased the MT-I+II immunoreactivity, peaking at ~3 dpl, and at 20 d pl it was similar to that of unlesioned mice. In situ hybridization analysis indicates that MT-I+II immunoreactivity reflects changes in the messenger levels. In MT-I+II null mice, microglia/macrophages infiltrated the lesion heavily, and at 20 dpl they were still present. Reactive astrocytosis was delayed and persisted at 20 dpl. in contrast to normal mice, at 20 dpl no wound healing had occurred. The rate of apoptosis, as determined by using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, was drastically increased in neurons of ipsilateral cortex of the MT-I+II null mice. Our results demonstrate that MT-I+II are essential for a normal wound repair in the CNS, and that their deficiency impairs neuronal survival.
Original languageEnglish
Pages (from-to)2535-2545
JournalJournal of Neuroscience
Issue number7
Publication statusPublished - 1 Apr 1999


  • Apoptosis
  • Astrocytes
  • Brain inflammation
  • Brain macrophages
  • Degeneration
  • MT-I+II
  • Neurons
  • Oxidative stress
  • Regeneration
  • Superoxide dismutase
  • Zinc


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