Brief Suppression of Abcc8 Prevents Autodestruction of Spinal Cord After Trauma
Year: 2010
Type: article
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 patterns 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.
Source: Science Translational Medicine
Authors: J. Marc Simard, S. Kyoon Woo, Michael D. Norenberg, Cigdem Tosun, Zheng Chen, Svetlana Ivanova, Orest Tsymbalyuk, Joseph Bryan, Douglas Landsman, Volodymyr Gerzanich
Language: English
Topic: Spinal Cord Injury Research
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G28512136, G5316128957, Astrocyte regulation of the blood-brain barrier in intracerebral hemorrhage, G6000446961, G6703938103, TrpM4 channel in spinal cord injury, Spinal cord injury, progressive hemorrhagic necrosis and the NC(Ca-ATP) channel, Pathological role of the SUR1-regulated NC(Ca-ATP) channel in cortex after subara
OpenAlex ID: W2153269370