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- Title
Antisense prevention of neuronal damages following head injury in mice.
- Authors
Shohami, E.; Kaufer, D.; Chen, Y.; Seidman, S.; Cohen, O.; Ginzberg, D.; Melamed-Book, N.; Yirmiya, R.; Soreq, H.
- Abstract
Closed head injury (CHI) is an important cause of death among young adults and a prominent risk factor for nonfamilial Alzheimer's disease. Emergency intervention following CHI should therefore strive to improve survival, promote recovery, and prevent delayed neuropathologies. We employed high-resolution nonradioactive in situ hybridization to determine whether a single intracerebroventricular injection of 500 ng 2′-O-methyl RNA-capped antisense oligonucleotide (AS-ODN) against acetylcholinesterase (AChE) mRNA blocks overexpression of the stress-related readthrough AChE (AChE-R) mRNA splicing variant in head-injured mice. Silver-based Golgi staining revealed pronounced dendrite outgrowth in somatosensory cortex of traumatized mice 14 days postinjury that was associated with sites of AChE-R mRNA overexpression and suppressed by anti-AChE AS-ODNs. Furthermore, antisense treatment reduced the number of dead CA3 hippocampal neurons in injured mice, and facilitated neurological recovery as determined by performance in tests of neuromotor coordination. In trauma-sensitive transgenic mice overproducing AChE, antisense treatment reduced mortality from 50% to 20%, similar to that displayed by head-injured control mice. These findings demonstrate the potential of antisense therapeutics in treating acute injury, and suggest antisense prevention of AChE-R overproduction to mitigate the detrimental consequences of various traumatic brain insults.
- Subjects
NEUROLOGICAL disorders; BRAIN injuries; ANTISENSE RNA; MESSENGER RNA; NERVOUS system; TRANSGENIC mice
- Publication
Journal of Molecular Medicine, 2000, Vol 78, Issue 4, p228
- ISSN
0946-2716
- Publication type
Article
- DOI
10.1007/s001090000104