Gene Expression Profile Changes are Commonly Modulated across Models and Species after Traumatic Brain Injury

JoAnne E Natale, Farid Ahmed, Ibolja Cernak, Bogdan Stoica, Alan I. Faden

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Brain trauma is a major cause of morbidity and mortality, both in adult and pediatric populations. Much of the functional deficit derives from delayed cell death resulting from induction of neurotoxic factors that overwhelm endogenous neuroprotective responses. To identify the potential molecular mechanisms underlying such delayed responses, we compared gene expression patterns using high-density oligonucleotide arrays at 4, 8, 24, and 72 h after moderate levels of lateral fluid percussion-induced brain injury in rats and lateral controlled cortical impact injury in mice (a total of 47 profiles). Expression of 82 genes in 12 functional categories was significantly changed in both species after trauma. The largest number of gene expression changes were found in the functional groups related to inflammation (17%), transcription regulation (16%), and cell adhesion/extracellular matrix (15%). Fifty percent of genes similarly altered across models had not been previously implicated in traumatic brain injury. Of particular interest were expression changes in genes linked to neurodegeneration, such as ATF3 and lysosomal membrane glycoprotein 2, and to neuroprotection including lipocortin 1, calponin 3, gelsolin, Id-1, and p45 NF-E2. Gene expression profiling across species and models may help identify candidate molecular pathways induced by brain injury, some of which may provide novel targets for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)907-927
Number of pages21
JournalJournal of Neurotrauma
Volume20
Issue number10
StatePublished - Oct 2003
Externally publishedYes

Keywords

  • Controlled cortical impact
  • Fluid percussion
  • Gene expression
  • MRNA

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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