Effect of U-50488h, a selective opioid κ receptor agonist, on vascular injury after spinal cord trauma

• Published in: Brain research Vol. 626; no. 1; pp. 45 - 49
• Main Authors: Qu, Zhi-Xiang, Xu, Jian, Hogan, Edward L., Hsu, Chung Y.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 29.10.1993; Amsterdam Elsevier; New York, NY
• Subjects: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Biological and medical sciences; Blood Vessels - drug effects; Blood Vessels - injuries; Capillary Permeability - drug effects; Disease Models, Animal; Edema; Edema - drug therapy; Female; Inflammation; Injuries of the nervous system and the skull. Diseases due to physical agents; Medical sciences; Neutrophil; Neutrophils - drug effects; Pyrrolidines - pharmacology; Rat; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa - drug effects; Sigma receptor; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - physiopathology; Spinal cord injury; Traumas. Diseases due to physical agents; Vascular permeability; Edema; Rat; Sigma receptor; Inflammation; Neutrophil; Spinal cord injury; Vascular permeability; Animal model; Agonist; Spinal cord; Rodentia; Central nervous system; Neuroprotective agent; Trauma; Opiate receptor κ; Vertebrata; Mammalia; Blood vessel; Circulatory system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(93)90561-Z

U-50488H, a selective opioid κ receptor agonist has been shown to be a neuroprotective agent in animal models of spinal cord injury. The mechanism of action of U-50488H is not known. Methylprednisolone, the only neuroprotective drug proven in patients with acute spinal cord injury may prevent the secondary injury after an initial trauma. Secondary vascular injury develops after experimental spinal cord trauma. In this study we examined the effects of U-50488H on post-traumatic vascular injury based on the measurement of vascular permeability, edema and neutrophil infiltration in a rat spinal cord injury model. Vascular permeability was assessed by vascular extravasation of fluorescein isothiocyanate conjugated dextran (FITC-D), a macromolecular tracer. Tissue edema was determined by percentage water content and neutrophil infiltration by myeloperoxidase (MPO) activity, a marker enzyme for neutrophils. U-50488H at doses of 5, 10, 20 and 40 mg/kg i.p. administered twice (0.5 h before and 0.5 h after trauma) reduced vascular permeability in a dose-dependent manner. More frequent dosing (10 mg/kg, 0.5 h before and 0.5, 2, 8 and 22 h after injury) reduced vascular permeability 24 h after injury. U-50488H also reduced edema formation but did not affect neutrophil infiltration. Results from this study raise the possibility that the neuroprotective effect of U-50488H involves a secondary vascular event.