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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
ATP-Binding Cassette Transporters / genetics
-
ATP-Binding Cassette Transporters / metabolism*
-
Animals
-
Disease Models, Animal
-
Gene Expression Regulation / drug effects
-
Glyburide / pharmacology
-
Hemorrhage / complications
-
Hemorrhage / pathology
-
Humans
-
Mice
-
Mice, Inbred C57BL
-
Necrosis
-
Potassium Channels, Inwardly Rectifying / deficiency
-
Potassium Channels, Inwardly Rectifying / genetics
-
Potassium Channels, Inwardly Rectifying / metabolism*
-
RNA, Antisense / metabolism
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Rats
-
Receptors, Drug / deficiency
-
Receptors, Drug / genetics
-
Receptors, Drug / metabolism*
-
Sp1 Transcription Factor / metabolism
-
Spinal Cord Injuries / pathology*
-
Spinal Cord Injuries / physiopathology
-
Spinal Cord Injuries / prevention & control*
-
Sulfonylurea Receptors
-
Treatment Outcome
Substances
-
ABCC8 protein, human
-
ATP-Binding Cassette Transporters
-
Abcc8 protein, mouse
-
Abcc8 protein, rat
-
Potassium Channels, Inwardly Rectifying
-
RNA, Antisense
-
RNA, Messenger
-
Receptors, Drug
-
Sp1 Transcription Factor
-
Sulfonylurea Receptors
-
Glyburide