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The Efficacy of Retrograde Infusion with LY231617 in a Rat Middle Cerebral Artery Occlusion Model

Published online by Cambridge University Press:  18 September 2015

Nobuhiro Inoue ,
Y. Lucas Yamamoto ,
Yasushi Ito ,
James A. Clemens ,
Jill K. Panetta  and
Mirko Diksic
Nobuhiro Inoue
Affiliation:
Kumamoto University Medical School, Kumamoto, Japan
Y. Lucas Yamamoto*
Affiliation:
Neuroisotope Laboratory and Cone Laboratory for Neurosurgical Research Montreal Neurological Institute, McGill University, Montreal
Yasushi Ito
Affiliation:
Niigata University Medical School, Niigata, Japan
James A. Clemens
Affiliation:
Lilly Research Laboratory, Eli Lilly and Company, USA
Jill K. Panetta
Affiliation:
Lilly Research Laboratory, Eli Lilly and Company, USA
Mirko Diksic
Affiliation:
Neuroisotope Laboratory and Cone Laboratory for Neurosurgical Research Montreal Neurological Institute, McGill University, Montreal
*
Neuroisotope Laboratory, Montreal Neruological Institute, 3801 University Street, Room 688, Montreal, Quebec, Canada H3A 2B4
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Abstract

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Background and Purpose: We examined the efficacy of the antioxidant LY231617 administered five hours following middle cerebral artery (MCA) occlusion in rats. Methods: The treatment was contrived for a two hour interval. Group A (n=16) was left untreated. Group B (n=16) received an intravenous infusion of LY231617. Group C (n=6) received saline (86 μI/min) by retrograde infusion of the cerebral vein (RICV). Group D (n=22) was administered LY231617 (10mg/kg/2hr) in saline (86μI/min) by RICV. Local cerebral blood flow with [14C]-iodoantipyrine and blood-brain transfer constant with 14C-α-amino-isobutyric acid were examined. Early ischemic damage was histologically examined with cresyl violet and Luxol fast blue and with triphenyl-tetrazolium chloride. Results: The results revealed a marked increase in local cerebral blood flow (over 600%, p < 0.01) after RICV with LY231617, with a significant improvement of BBB permeability in rats from group D. Ischemic brain damage measured with Luxol fast blue and triphenyl-tetrazolium chloride methods showed a significant improvement (50-91 %) of ischemic damage in group D, as compared to groups B and C. Conclusion: Retrograde infusion of the cerebral vein with LY231617 resulted in a significant amelioration at seven hours post MCA occlusion.

Résumé

Résumé

Efficacité d’une infusion rétrograge de LY231617 chez le rat comme modèle expérimental d’occlusion de l’artère cérébrale moyenne. Introduction: Nous avons évalué l’efficacité du LY231617, un antioxidant, injecté 5 heures après l’occlusion de l’artère cérébrale moyenne (ACM) chez le rat. Méthodes: La durée du traitement était de deux heures. Le groupe A (n=16) n’était pas traité. Le groupe B (n=16) a reçu une infusion intraveineuse de LY231617. Le groupe C (n=6) a reçu du salin (86 (μI/min) par infusion rétrograde dans la veine cérébrale (IRVC). Le groupe D (n=22) a reçu le LY231617 (10 mg/kg/2hrs) dans du salin (86 (il/min) par IRVC. Nous avons évalué le flot sanguin cérébral local (FSCL) au moyen de la [14C]-iodoantipyrine et la constante de transfert hémato-encéphalique au moyen de l’acide [14C]-α-amino-isobutyrique. Le dommage ischémique précoce a été évalué par coloration his-tologique au violet de crésyl et au bleu de Luxol (CL) et au chlorure de triphényl-tétrazolium (CTT). Résultats: Nous avons constaté une augmentation marquée du FSCL (plus de 600%, p<0.01) après l’IRVC au LY231617, accompagnée d’une amélioration significative de la perméabilité de la barrière hémato-encéphalique chez les rats du groupe D. L’évaluation des dommages ischémiques cérébraux par CL et CTT a montré une amélioration significative (50-91 ir) des dommages ischémiques dans le groupe D par rapport aux groupes B et C. Conclusion: Le traitement par IRVC de LY231617 a entraîné une amélioration significative 7 heures après l’occlusion de l’ACM.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 23 , Issue 3 , August 1996 , pp. 175 - 183
Copyright
Copyright © Canadian Neurological Sciences Federation 1996

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