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 ce ntral role in post-traumatic cell death was shown to be differentially alte red in response to a precisely controlled, mechanical injury applied to an organotypic slice culture of the rat brain. Within 48 h of injury, the expr ession of nerve growth factor messenger RNA was significantly increased whe reas the levels of bcl-2, alpha-subunit of calcium/calmodulin-dependent pro tein kinase II, cAMP response element binding protein, 65,000 mel. wt isofo rm of glutamate decarboxylase, 1 beta isoform of protein kinase C, and ubiq uitin messenger RNA were significantly decreased. Because the expression le vels of a number of other messenger RNAs such as the neuron-specific amyloi d precursor protein, beta(2) microglobulin, bax, bcl(xl), brain-derived neu rotrophic factor, cyclooxygenase-2, interleukin-1 beta, interleukin-6, tumo r 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 tra uma. Interpretation of these co-ordinated alterations suggests that mechanical i njury to the central nervous system may lead to disruption of calcium homeo stasis resulting in altered gene expression, an impairment of intracellular cascades responsible for trophic factor signaling, and initiation of apopt osis via multiple pathways. An understanding of these transcriptional chang es may contribute to the development of novel therapeutic strategies to enh ance beneficial and blunt detrimental, endogenous, post-injury response mec hanisms. (C) 2000 IBRO. Published by Elsevier Science Ltd.