SB209670, a potent endothelin receptor antagonist, prevents or delays axonal degeneration after spinal cord injury.
We developed a rat spinal cord transection injury model and investigated whether endogenous endothelin takes part in axonal degeneration after injury, by using a potent nonselective endothelin receptor antagonist, SB209670. Light microscopic analysis showed that axonal degeneration of the spinal cord was clearly observed one week after injury, supported by immunohistochemical study with anti-neurofilament antibody. Electron microscopic observation showed enlargement and shrinking of spinal axons in the injured sites one week after injury. Application of SB209670 to the lesion sites markedly inhibited axonal damage after injury. These results suggest that endogenous endothelin plays a role in axonal degeneration after spinal cord injury and that SB209670 prevents or delays the axonal degeneration after CNS damage.
Uesugi
M
M
Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305, Japan.
Kasuya
Y
Y
Hayashi
K
K
Goto
K
K
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D065128:Endothelin Receptor Antagonists; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000473:pathology* / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology*; D013997:Time Factors
D065128:Endothelin Receptor Antagonists; D007189:Indans; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-