Traumatic injury induces differential expression of cell death genes in organotypic brain slice cultures determined by complementary DNA array hybridization.
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 mol. wt isoform of glutamate decarboxylase, 1beta 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-1beta, 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.
Morrison
B
B
Department of Bioengineering, University of Pennsylvania, Philadelphia 19104, USA.
Eberwine
J H
JH
Meaney
D F
DF
McIntosh
T K
TK
D000818:Animals; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013314:Stress, Mechanical
D018076:DNA, Complementary; D012333:RNA, Messenger