Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma

J. Marc Simard, S. Kyoon Woo, Michael D. Norenberg, Cigdem Tosun, Zheng Chen, Svetlana Ivanova, Orest Tsymbalyuk, Joseph Bryan, Douglas Landsman, Volodymyr Gerzanich

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Spinal cord injury (SCI) is typically complicated by progressive hemorrhagic necrosis, an autodestructive process of secondary injury characterized by progressive enlargement of a hemorrhagic contusion during the first several hours after trauma. We assessed the role of Abcc8, which encodes sulfonylurea receptor 1 (SUR1), in progressive hemorrhagic necrosis. After SCI, humans and rodents exhibited similar regional and cellular pattems of up-regulation of SUR1 and Abcc8 messenger RNA. Elimination of SUR1 in Abcc8 -/- mice and in rats given antisense oligodeoxynucleotide against Abcc8 prevented progressive hemorrhagic necrosis, yielded significantly better neurological function, and resulted in lesions that were one-fourth to one-third the size of those in control animals. The beneficial effects of Abcc8 suppression were associated with prevention of oncotic (necrotic) death of capillary endothelial cells. Suppression of Abcc8 with antisense oligodeoxynucleotide after SCI presents an opportunity for reducing the devastating sequelae of SCI.

Original languageEnglish (US)
Pages (from-to)28ra29
JournalScience Translational Medicine
Volume2
Issue number28
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Medicine(all)

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    Simard, J. M., Woo, S. K., Norenberg, M. D., Tosun, C., Chen, Z., Ivanova, S., Tsymbalyuk, O., Bryan, J., Landsman, D., & Gerzanich, V. (2010). Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma. Science Translational Medicine, 2(28), 28ra29. https://doi.org/10.1126/scitranslmed.3000522