Novel roles for metallothionein-I + II (MT-I + II) in defense responses, neurogenesis, and tissue restoration after traumatic brain injury: Insights from global gene expression profiling in wild-type and MT-I + II knockout mice

Milena Penkowa, Mario Cáceres, Rehannah Borup, Finn Cilius Nielsen, Christian Bjørn Poulsen, Albert Quintana, Amalia Molinero, Javier Carrasco, Sergi Florit, Mercedes Giralt, Juan Hidalgo*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

42 Citations (Scopus)

Abstract

Traumatic injury to the brain is one of the leading causes of injury-related death or disability, especially among young people. Inflammatory processes and oxidative stress likely underlie much of the damage elicited by injury, but the full repertoire of responses involved is not well known. A genomic approach, such as the use of microarrays, provides much insight in this regard, especially if combined with the use of gene-targeted animals. We report here the results of one of these studies comparing wild-type and metallothionein-I + II knockout mice subjected to a cryolesion of the somatosensorial cortex and killed at 0, 1, 4, 8, and 16 days postlesion (dpl) using Affymetrix genechips/oligonucleotide arrays interrogating ∼10,000 different murine genes (MG_U74Av2). Hierarchical clustering analysis of these genes readily shows an orderly pattern of gene responses at specific times consistent with the processes involved in the initial tissue injury and later regeneration of the parenchyma, as well as a prominent effect of MT-I + II deficiency. The results thoroughly confirmed the importance of the antioxidant proteins MT-I + II in the response of the brain to injury and opened new avenues that were confirmed by immunohistochemistry. Data in KO, MT-I-overexpressing, and MT-II-injected mice strongly suggest a role of these proteins in postlesional activation of neural stem cells. © 2006 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)1452-1474
JournalJournal of Neuroscience Research
Volume84
DOIs
Publication statusPublished - 15 Nov 2006

Keywords

  • Affymetrix microarrays
  • Metallothionein-I + II deficiency
  • Murine genome
  • Traumatic brain injury

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