Journal
NEUROSCIENCE
Volume 96, Issue 1, Pages 131-139Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0306-4522(99)00537-0
Keywords
genomic expression; in vitro model; traumatic brain injury; organotypic culture; stretch injury; cDNA array
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Funding
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM034690] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS008803, R01NS026818] Funding Source: NIH RePORTER
- NIGMS NIH HHS [R01-GM34690] Funding Source: Medline
- NINDS NIH HHS [P01-NS08803, R01-NS26818] Funding Source: Medline
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The expression of a large panel of selected genes hypothesized to play a central role in post-traumatic cell death was shown to be differentially altered in response to a precisely controlled, mechanical injury applied to an organotypic slice culture of the rat brain. Within 48 h of injury, the expression of nerve growth factor messenger RNA was significantly increased whereas the levels of bcl-2, alpha-subunit of calcium/calmodulin-dependent protein kinase II, cAMP response element binding protein, 65,000 mel. wt isoform of glutamate decarboxylase, 1 beta isoform of protein kinase C, and ubiquitin messenger RNA were significantly decreased. Because the expression levels of a number of other messenger RNAs such as the neuron-specific amyloid precursor protein, beta(2) microglobulin, bax, bcl(xl), brain-derived neurotrophic factor, cyclooxygenase-2, interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, receptor tyrosine kinase A, and receptor tyrosine kinase B were unaffected, these selective changes may represent components of an active and directed response of the brain initiated by mechanical trauma. Interpretation of these co-ordinated alterations suggests that mechanical injury to the central nervous system may lead to disruption of calcium homeostasis resulting in altered gene expression, an impairment of intracellular cascades responsible for trophic factor signaling, and initiation of apoptosis via multiple pathways. An understanding of these transcriptional changes may contribute to the development of novel therapeutic strategies to enhance beneficial and blunt detrimental, endogenous, post-injury response mechanisms. (C) 2000 IBRO. Published by Elsevier Science Ltd.
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