Mild traumatic brain injury-induced hippocampal gene expressions: The identification of target cellular processes for drug development

J Neurosci Methods. 2016 Oct 15;272:4-18. doi: 10.1016/j.jneumeth.2016.02.003. Epub 2016 Feb 8.

Abstract

Background: Neurological dysfunction after traumatic brain injury (TBI) poses short-term or long-lasting health issues for family members and health care providers. Presently there are no approved medicines to treat TBI. Epidemiological evidence suggests that TBI may cause neurodegenerative disease later in life. In an effort to illuminate target cellular processes for drug development, we examined the effects of a mild TBI on hippocampal gene expression in mouse.

Methods: mTBI was induced in a closed head, weight drop-system in mice (ICR). Animals were anesthetized and subjected to mTBI (30g). Fourteen days after injury the ipsilateral hippocampus was utilized for cDNA gene array studies. mTBI animals were compared with sham-operated animals. Genes regulated by TBI were identified to define TBI-induced physiological/pathological processes. mTBI regulated genes were divided into functional groupings to provide gene ontologies. Genes were further divided to identify molecular/cellular pathways regulated by mTBI.

Results: Numerous genes were regulated after a single mTBI event that mapped to many ontologies and molecular pathways related to inflammation and neurological physiology/pathology, including neurodegenerative disease.

Conclusions: These data illustrate diverse transcriptional changes in hippocampal tissues triggered by a single mild injury. The systematic analysis of individual genes that lead to the identification of functional categories, such as gene ontologies and then molecular pathways, illustrate target processes of relevance to TBI pathology. These processes may be further dissected to identify key factors that can be evaluated at the protein level to highlight possible treatments for TBI in human disease and potential biomarkers of neurodegenerative processes.

Keywords: Dementia; Gene expression; Gene ontology; Inflammation; Mild traumatic brain injury (mTBI); Molecular pathway; Neurodegeneration; Neurological.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Concussion / metabolism*
  • Computational Biology
  • Disease Models, Animal
  • Drug Discovery
  • Functional Laterality
  • Gene Expression Regulation
  • Gene Ontology
  • Hippocampus / metabolism*
  • Mice, Inbred ICR
  • Microarray Analysis
  • Transcription, Genetic