Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-29T04:19:19.680Z Has data issue: false hasContentIssue false
  • English
  • Français

Failure of Iron Chelators to Protect Against Cerebral Infarction in Hypoxia-Ischemia

Published online by Cambridge University Press:  18 September 2015

V. MacMillan ,
I. Fridovich  and
J. Davis
V. MacMillan*
Affiliation:
Division of Neurology, University of Toronto, Toronto (V.M.); and Departments of Biochemistry (I.F.) and Medicine (Neurology) (J.D.), Duke University, Durham, U.S.A.
I. Fridovich
Affiliation:
Division of Neurology, University of Toronto, Toronto (V.M.); and Departments of Biochemistry (I.F.) and Medicine (Neurology) (J.D.), Duke University, Durham, U.S.A.
J. Davis
Affiliation:
Division of Neurology, University of Toronto, Toronto (V.M.); and Departments of Biochemistry (I.F.) and Medicine (Neurology) (J.D.), Duke University, Durham, U.S.A.
*
Room 6366, Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada M5S IA8
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

In this study the ability of iron chelators to attenuate hypoxic-ischemic brain damage was assessed in hyperglycemic rats that were exposed to 1% carbon monoxide and right carotid occlusion. The animals received deferoxamine (50 mg/kg), manganese-deferoxamine (50 mg/kg) or vehicle i.p. 0.5 h prior to hypoxemic-ischemic exposure and at 0.5, 3 and 24 h post-exposure; with subsequent histological examination of the brain at 7 days recovery. The area of cerebral infarction was measured at three levels using video imaging methods. The mean percentage of total hemisphere that was infarcted in the three groups was: vehicle — 28.5 ± 5.0; deferoxamine — 31.7 ± 12.1; and manganese deferoxamine — 30.6 ± 6.8 (p - n.s.). The results as obtained in this preliminary study indicate that aggressive pre- and post-treatment with iron chelators has no ability to attenuate cerebral infarction in this model.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 20 , Issue 1 , February 1993 , pp. 41 - 43
Copyright
Copyright © Canadian Neurological Sciences Federation 1993

References

1.White, BC, Aust, SD, Arfors, KE, et al.Brain injury by ischemic anoxia: hypothesis extension — a tale of two ions? Ann Emerg Med 1984; 13: 862–867.CrossRefGoogle ScholarPubMed
2.Babbs, CF. Role of iron ions in the genesis of reperfusion injury following successful cardiopulmonary resuscitation: preliminary data and a biochemical hypothesis. Ann Emerg Med 1985; 14: 777–783.CrossRefGoogle Scholar
3.Siesjo, BK, Agardh, CD, Bengtsson, F.Free radicals and brain damage. Cereb Brain Metab Rev 1989; 1: 165–211.Google ScholarPubMed
4.Aust, SD, Svingen, BA.The role of iron in enzymatic lipid peroxidation. Free Radicals Biol 1982; 5: 1–28.Google Scholar
5.Siesjo, BK, Bendek, G, Koide, T, et al.Influence of acidosis on lipid peroxidation in brain tissues in vitro. J Cereb Blood Flow Metab 1985; 5: 253–258.CrossRefGoogle ScholarPubMed
6.Rehncrona, S, Hauge, HN, Siesjo, BK.Enhancement of iron-catalyzed free radical formation by acidosis in brain homogenates: difference in effect by lactic acid and C02. J Cereb Blood Flow Metab 1989; 9: 65–70.CrossRefGoogle Scholar
7.Kompala, SD, Babbs, CF, Blaho, KE.Effect of deferoxamine on late deaths following CPR in rats. Ann Emerg Med 1986; 15: 405–407.CrossRefGoogle ScholarPubMed
8.Komara, JS, Nayini, NR, Bialick, HA, et al.Brain iron derealization and lipid peroxidation following cardiac arrest. Ann Emerg Med 1986; 15: 384–389.CrossRefGoogle Scholar
9.Badylak, SF, Babbs, CFR.The effect of carbon dioxide. Ikloflazine and deferoxamine upon long term survival following cardiorespiratory arrest in rats. Resuscitation 1986; 13: 165–173.CrossRefGoogle ScholarPubMed
10.Cerchiari, EL, Holl, TM, Safar, F, et al.Protective effects of combined superoxide dismutase and deferoxamine on recovery of cerebral blood flow and function after cardiac arrest in dogs. Stroke 1987; 18: 869–878.CrossRefGoogle ScholarPubMed
11.Konig, FR, Klippel, RA.The Rat Brain: A Stereotaxic Atlas. Williams and Wilkins Company, Baltimore, 1963.Google Scholar
12.MacMillan, V.Cerebral energy metabolism during recovery from carbon monoxide hypoxia-oligemia. Brain Res 1978; 151: 353–368.CrossRefGoogle ScholarPubMed
13.Fleischer, JE, Lanier, WL, Milde, JH, et al.Failure of deferoxamine, an iron chelator, to improve neurologic outcome following complete cerebral ischemia in dogs. Stroke 1987; 18: 124–127.CrossRefGoogle ScholarPubMed
14.Garavilla, L de, Chermak, T, Valentine, HL.et al.The superoxide dismutase (SOD) mimic manganese-deferoxamine (Mn-DFO) improves survival following hemorrhagic and endotoxic shock. FASEB J 1990; 4: A626.Google Scholar
15.MacMillan, V.Cerebral carbohydrate metabolism during acute carbon monoxide intoxication. Brain Res 1977; 121: 271–286.CrossRefGoogle ScholarPubMed
16.Salford, LG, Plum, F, Siesjo, BK.Graded hypoxemia-oligemia in rat brain: I. Biochemical alterations and their implications. Arch Neurol (Chic) 1973; 29: 227–233.CrossRefGoogle Scholar
17.Kalimo, H, Rehncrona, S, Soderfeldt, B, et al.Brain lactic acidosis and ischemic cell damage: 2. Histopathology. J Cereb Blood Flow Metab 1981; 1:313–327.CrossRefGoogle ScholarPubMed