Treatment of Brain Edema with a Nonpeptide Arginine Vasopressin V1 Receptor Antagonist OPC-21268 in Rats

Treatment of Brain Edema with a Nonpeptide Arginine Vasopressin V1 Receptor Antagonist OPC-21268... AbstractOBJECTIVERecent experimental evidence suggests that centrally released arginine vasopressin plays a significant role in brain capillary water permeability as well as in pathogenesis of vasogenic brain edema. The purpose of this study was to examine the effects of orally administered OPC-21268, a nonpeptide arginine vasopressin receptor antagonist, on cold-induced brain edema in rats.METHODSCold brain injury was induced for 1 minute in 140 rats. Treatment with OPC-21268, at dosages of 100 mg (n = 20), 200 mg (n = 20), and 300 mg/kg (n = 15), or with saline (n = 17) was started 1 hour after the induction of cold injury and was continued every 8 hours for 24 hours. Two percent Evans blue in saline (1 ml/kg) was administered intravenously before cold injury in another group of rats, 15 of which were saline-treated and 55 of which were OPC-21268-treated at the above dosages. After 24 hours, brain tissue water and electrolytes, brain tissue swelling, blood-brain barrier permeability to Evans blue, and plasma electrolytes and osmolality were determined.RESULTSCompared with the saline-treated group, OPC-21268 treatment at the dosages of 200 and 300 mg/kg significantly reduced brain water content in both hemispheres (P < 0.01). Swelling of the traumatized hemispheres was also significantly reduced at 200 and 300 mg/kg dosages (P < 0.05). Brain tissue sodium content was significantly reduced at the dosage of 300 mg/kg (P < 0.05). Blood-brain barrier permeability to Evans blue was significantly decreased in a dose-dependent manner compared with the saline-treated group (P < 0.01). No significant changes were observed in other parameters.CONCLUSIONOur results indicate that OPC-21268 predominantly exerts a protective effect in areas where the maximum amount of blood-brain barrier breakdown occurs, and it is effective in the treatment of cold-induced vasogenic brain edema. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Treatment of Brain Edema with a Nonpeptide Arginine Vasopressin V1 Receptor Antagonist OPC-21268 in Rats

Treatment of Brain Edema with a Nonpeptide Arginine Vasopressin V1 Receptor Antagonist OPC-21268 in Rats

Treatment of Brain Edema with a Nonpeptide Arginine Vasopressin Receptor Antagonist OPC-21268 in Rats Iraj Bemana, M .D ., Seigo Nagao, M .D ., Ph.D. Department of Neurological Surgery, Kagawa Medical University, Kagawa, Japan O B JEC TIV E: Recent experimental evidence suggests that centrally released arginine vasopressin plays a significant role in brain capillary water permeability as well as in pathogenesis of vasogenic brain edema. The purpose of this study was to examine the effects of orally administered O P C -2 1 2 6 8 , a nonpeptide arginine vasopressin receptor antagonist, on cold-induced brain edema in rats. M E T H O D S : Cold brain injury was induced for 1 minute in 140 rats. Treatment with O P C -2 1 2 6 8 , at dosages of 100 mg (n = 20), 200 mg (n = 20), and 300 mg/kg (n = 15), or with saline (n = 17) was started 1 hour after the induction of cold injury and was continued every 8 hours for 24 hours. Two percent Evans blue in saline (1 ml/kg) was administered intravenously before cold injury in another group of rats, 15 of w hich were saline-treated and 55 of which were OPC-21268-treated at the above dosages. After 24 hours, brain tissue water and electrolytes, brain tissue swelling, blood-brain barrier permeability to Evans blue, and plasma electrolytes and osmolality were determined. RESULTS: Compared with the saline-treated group, OPC-21268 treatment at the dosages of 200 and 300 mg/kg significantly reduced brain water content in both hemispheres (P < 0.01). Swelling of the traumatized hemispheres was also significantly reduced at 200 and 300 mg/kg dosages (P < 0.05). Brain tissue sodium content was significantly reduced at the dosage of 300 mg/kg (P < 0.05). Blood-brain barrier permeability to Evans blue was signifi­ cantly decreased in a dose-dependent manner compared with the saline-treated group (P < 0.01). No significant changes were observed in other parameters. C O N C L U S I O N : O u r results indicate that O P C -2 1...
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Publisher
Oxford University Press
Copyright
© Published by Oxford University Press.
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1097/00006123-199901000-00091
Publisher site
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Abstract

AbstractOBJECTIVERecent experimental evidence suggests that centrally released arginine vasopressin plays a significant role in brain capillary water permeability as well as in pathogenesis of vasogenic brain edema. The purpose of this study was to examine the effects of orally administered OPC-21268, a nonpeptide arginine vasopressin receptor antagonist, on cold-induced brain edema in rats.METHODSCold brain injury was induced for 1 minute in 140 rats. Treatment with OPC-21268, at dosages of 100 mg (n = 20), 200 mg (n = 20), and 300 mg/kg (n = 15), or with saline (n = 17) was started 1 hour after the induction of cold injury and was continued every 8 hours for 24 hours. Two percent Evans blue in saline (1 ml/kg) was administered intravenously before cold injury in another group of rats, 15 of which were saline-treated and 55 of which were OPC-21268-treated at the above dosages. After 24 hours, brain tissue water and electrolytes, brain tissue swelling, blood-brain barrier permeability to Evans blue, and plasma electrolytes and osmolality were determined.RESULTSCompared with the saline-treated group, OPC-21268 treatment at the dosages of 200 and 300 mg/kg significantly reduced brain water content in both hemispheres (P < 0.01). Swelling of the traumatized hemispheres was also significantly reduced at 200 and 300 mg/kg dosages (P < 0.05). Brain tissue sodium content was significantly reduced at the dosage of 300 mg/kg (P < 0.05). Blood-brain barrier permeability to Evans blue was significantly decreased in a dose-dependent manner compared with the saline-treated group (P < 0.01). No significant changes were observed in other parameters.CONCLUSIONOur results indicate that OPC-21268 predominantly exerts a protective effect in areas where the maximum amount of blood-brain barrier breakdown occurs, and it is effective in the treatment of cold-induced vasogenic brain edema.

Journal

NeurosurgeryOxford University Press

Published: Jan 1, 1999

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