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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
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
Copyright
Copyright © Canadian Neurological Sciences Federation 1996

References

1. Hall, ED., Travis, MA. Inhibition of arachidonic acid-induced vasogenic brain edema by the non-glucocorticoid 21-aminosteroid U74006F. Brain Res 1988a; 451: 350352.Google Scholar
2. Hossmann, KA. Calcium antagonist for the treatment of brain ischemia: a critical appraisal. In: Krieglstein, J., ed. Pharmacology of Cerebral Ischemia. Stuttgart, Wissenschaftliche Verlagsgesellschaft, 1988: 5363.Google Scholar
3. Morikawa, E., Ginsbert, MD., Dietrich, WD., Duncan, RC., Busto, R. Postischemic (S)-Emopamil therapy ameliorates focal ischemic brain injury in rats. Stroke 1991; 22: 355360.CrossRefGoogle ScholarPubMed
4. Barsan, WG., Brott, TG., Olinger, CP., Marlar, JR. Early treatment for acute ischemic stroke. Ann Intern Med 1989; 111: 449451.CrossRefGoogle ScholarPubMed
5. Ueda, T., Yamamoto, YL., Takara, E., Diksic, M. Tolerance of the cerebral venous system to retrograde perfusion pressure in focal cerebral ischemia in rats. Stroke 1989a; 20: 378385.CrossRefGoogle Scholar
6. Ueda, T., Yamamoto, YL., Diksic, M. Transvenous perfusion of the brain with verapamil during focal cerebral ischemia in rats. Stroke 1989b; 20: 501506.CrossRefGoogle Scholar
7. Hosaka, T., Yamamoto, YL., Diksic, M. Efficacy of retrograde perfusion of the cerebral vein with verapamil after focal ischemia in rat brain. Stroke 1991; 22: 15621566.CrossRefGoogle ScholarPubMed
8. Shimauchi, M., Yamamoto, YL. Effects of retrograde perfusion of the brain with combined drug therapy after focal ischemia in rat brain. Stroke 1992; 23: 18051811.CrossRefGoogle ScholarPubMed
9. Beckman, JS., Liu, TH., Hogan, EL., et al. Evidence for a role of oxygen radicals in cerebral ischemic injury. In: Ginsbert, MD., Dietrich, WD., eds. Cerebrovascular Diseases. New York: Raven Press, 1989: 373380.Google Scholar
10. Chan, PK., Schimdley, JW., Fishman, RA., Longar, SM. Brain injury, edema, and vascular permeability changes induced by oxygen-derived free radicals. Neurology 1984; 34: 315320.CrossRefGoogle ScholarPubMed
11. Clemens, JA., Ho, PP., Panetta, JA. LY178002 reduces rat brain damage after transient global forebrain ischemia. Stroke 1991; 22: 10481052.CrossRefGoogle ScholarPubMed
12. Clemens, JA., Saunder, RD., Ho, PP., Panetta, JA. The antioxidant, LY231617, reduces global ischemic neuronal injury in rats. Stroke 1993; 24: 716723.CrossRefGoogle ScholarPubMed
13. Kontos, HA. Oxygen radicals in cerebral ischemia. In: Ginsberg, MD., Dietrich, WD., eds. Cerebrovascular Diseases. 16th Princeton Conferences. New York: Raven Press, 1989: 365371.Google Scholar
14. McCord, JM. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 1985; 312: 159163.Google ScholarPubMed
15. Oliver, CN., Starke-Reed, DE., Stadtman, ER., et al. Oxidative damage to brain proteins loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc Nat Acad Sci USA 1990; 87: 51445147.CrossRefGoogle ScholarPubMed
16. Siesjö, BK., Agardh, CD., Bengtsson, F. Free radicals and brain damage. Cereb Brain Metab 1989; 1: 165211.Google ScholarPubMed
17. Siesjö, BK., Lundgren, J., Pahlmark, K. The role of free radicals in ischemic brain damage: a hypothesis. In: Krieglstein, J., Oberpichler, H., eds. Pharmacology of Cerebral Ischemia. Stuttgart, Wissenschaftliche Verlagsgesellschaft, 1990: 319323.Google Scholar
18. Swanson, RA., Morton, MT., Tsao-Wu, G., et al. A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab 1990; 10: 290293.CrossRefGoogle ScholarPubMed
19. Uemura, A., Mabe, H., Nagai, H., Sugino, F. Action of phospholipase A2 and C on free fatty acid release during complete ischemia in rat neocortex. J Neurosurg 1992; 76: 648651.CrossRefGoogle Scholar
20. Araki, N., Greenberg, JH., Uematsu, D., Sladky, JT., Reivich, M. Effect of superoxide dismutase on intracellular calcium in stroke. J Cereb Blood Flow Metab 1992; 12: 4352.CrossRefGoogle ScholarPubMed
21. Cerchiari, EL., Hoel, TH., Safar, P., Sclabassi, RJ. Protective effects of combined superoxide dismutase and defroxamine on recovery of cerebral blood flow and function after cardiac arrest in dogs. Stroke 1987; 18: 869878.CrossRefGoogle Scholar
22. Liu, TH., Beckman, JS., Freeman, BA., Hogan, EL., Hsu, CY. Polyethylene glycolconjugated superoxide dismutase and catalase reduce ischemic brain injury. Am J Physiol 1989; 256: H589H593.Google ScholarPubMed
23. Martz, D., Rayos, G., Schielke, GP., Betz, AL. Allopurinol and dimethylthiorea reduce brain infarction following middle cerebral artery occlusion in rats. Stroke 1989; 20: 488494.CrossRefGoogle Scholar
24. Martz, D., Beer, M., Betz, AL. Dimethylthiorea reduces ischemic brain edema without affecting cerebral blood flow. J Cereb Blood Flow Metab 1990; 10: 352357.CrossRefGoogle Scholar
25. Lesiuk, H., Sutherland, G., Peeling, J., Butler, K., Saunders, J. Effect of U74006F on forebrain ischemia in rats. Stroke 1991; 22: 896901.CrossRefGoogle ScholarPubMed
26. Young, W., Wojak, JC., DeCrescito, V. 21-aminosteroid reduces ion shifts and edema in the rat middle cerebral artery occlusion model of regional ischemia. Stroke 1988; 19: 10131019.CrossRefGoogle ScholarPubMed
27. Tamura, A., Graham, DI., McColluch, J., Teasdale, GM. Focal cerebral ischemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1981; 1: 5360.CrossRefGoogle ScholarPubMed
28. Paxinos, G., and Watson, C., eds. The Rat Brain in Stereotaxic Coordinates, 7th edn., New York: Academic Press, Inc., 1986.Google Scholar
29. Osborne, KA., Shigeno, T., Balarsky, AM., et al. Quantitative assessment of early brain damage in a rat model of focal cerebral ischemia. J Neurol Neurosurg Psychiatry 1987; 50: 402410.CrossRefGoogle Scholar
30. Bederson, JB., Pitts, CH., Sabelle, M., et al. Evaluation of 2, 3, 5, Triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke 1986; 17: 13041308.CrossRefGoogle ScholarPubMed
31. Park, CK., Mendelow, AD., Graham, DI., McCulloch, J., Teasdale, GM. Correlation of triphenyltetrazolium chloride perfusion staining with conventional neurohistology in the detection of early brain edema. Neuropathol and Appl Neurobiol 1988; 14: 289298.CrossRefGoogle Scholar
32. Lin, TN., He, YY., Wu, G., Khan, M., Hsu, CY. Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke 1993; 24: 117121.CrossRefGoogle Scholar
33. Blasbert, RG., Patlak, CS., Fenstermacher, JD. Selection of experimental conditions for the accurate determination of blood-brain transfer constants from single-time experiments: a theoretical analysis. J Cereb Blood How Metab 1983; 3: 215225.CrossRefGoogle Scholar
34. Hatfield, RH., Mendelow, AD., Perry, RH., Alvarezs, LM., Modha, P. Triphenyltetrazolium chloride (TTC) as a marker for ischemic changes in rat brain following permanent middle cerebral artery occlusions. Neuropathol Appl Neurobiol 1991; 17: 6167.CrossRefGoogle Scholar
35. Ginsberg, MD. Efficacy of calcium channel blockers in brain ischemia – a critical assessment. In: Krieglstein, J., ed. Pharmacology of Cerebral Ischemia. Stuttgart, Wissenschaftliche Verlagsgesellschaft 1988: 6573.Google Scholar
36. Sakurada, O., Kennedy, C., Jehle, J., et al. Measurement of local cerebral blood flow with iodo[14C]antipyrine. Am J Physiol 1978; 234: H59H66.Google ScholarPubMed
37. Schmidley, JW. Free radicals in central nervous system ischemia. Stroke 1990; 21: 10861090.CrossRefGoogle ScholarPubMed
38. Hall, ED., Yonkers, PA. Attenuation of postischemic cerebral hypoperfusion by the 21-aminosteroid U74006F. Stroke 1988b; 19: 340344.CrossRefGoogle Scholar
39. Abe, K., Yuki, S., Kogure, K. Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger. Stroke 1988; 19: 480485.CrossRefGoogle ScholarPubMed
40. Xue, D., Slivka, A., Buchan, AM. Tirilazad reduces cortical infarction after transient but not permanent focal cerebral ischemia in rats. Stroke 1992; 23: 894899.CrossRefGoogle Scholar
41. Oh, SM., Betz, AL. Interaction between free radicals and excitatory amino acids in the formation of ischemic brain edema in rats. Stroke 1991; 22: 915921.CrossRefGoogle ScholarPubMed
42. Hassler, O. Deep cerebral venous system in man. A microangiographic study on its areas of drainage and its anastomoses with the superficial cerebral veins. Neurology (Minneap.) 1966; 16: 505511.CrossRefGoogle Scholar
43. Yamamoto, YL., Ueda, T., Shimauchi, M., Diksic, M. Efficacy of bypass between extracerebral artery and cerebral vein with retrograde verapamil infusion into focal cerebral ischemia in rats. Neurosurgery 1991; 29: 719726.CrossRefGoogle ScholarPubMed
44. Willmore, LJ., Rubin, JJ. Formation of malonaldehyde and focal brain edema induced by subpial of FeCI2 into rat isocortex. Brain Res 1982; 246: 113119.CrossRefGoogle Scholar
45. Wei, HM., Chi, OZ., Liu, X., Sinlia, AK., Weiss, HR. Nitric oxide synthase inhibition after cerebral blood flow and oxygen balance in focal cerebral ischemia in rats. Stroke 1994; 25: 445450.CrossRefGoogle ScholarPubMed
46. Ito, Y., Leblanc, R., Yamamoto, YL. Effect of retroinfusion of LY231617 in monkeys. (In preparation.)Google Scholar
47. Yamamoto, YL., Ueda, T. Effective delivery of cytoprotective agent into the ischemic tissue following the retrograde intracerebral venous infusion of vasodilator. (In Press).Google Scholar
48. Nagao, T., Yamamoto, YL., Inoue, N., Ito, Y. Retrograde perfusion of the cerebral vein with antioxidant LY231617 reduces brain damage in rat focal ischemia model. Neurol Med Chir 1995; 35: 851.CrossRefGoogle ScholarPubMed
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