Outstanding Neuroprotective Efficacy of Dexrazoxane in Mice Subjected to Sequential Common Carotid Artery Sectioning

Rodolfo Rodriguez, Jacinto Santiago-Mejia, Monica Fuentes-Vargas, Eduardo Ramirez San-Juan

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

We evaluated the efficacy of the iron chelator, dexrazoxane, to reduce the neurological alterations and mortality produced by sequential common carotid artery sectioning (SCAS) in mice. Deferoxamine (32 and 128 mg/kg), dexrazoxane (32 and 128 mg/kg), dizolcipine (0.8 and 3.2 mg/kg), or nimodipine (0.4 and 1.6 mg/kg) were injected ip 15 min after the second artery sectioning. Animals were evaluated at 24, 48, and 72 h after compound or vehicle injection using three procedures: neurological examination, spontaneous locomotor activity, and motor coordination. Based on neurological evaluation, we designed and used a disability status scale (NDSS) to determine the degree of functional incapacity after brain ischemia for each animal. The scale comprises 10 progressive grades or steps beyond 0 (normal), extending to status 10 (death due to SCAS). In this scale, the higher the number, the greater is the neurological dysfunction. For the vehicle-treated animals, the survival rate ranged from 41 to 30% and the neurological scores ranged from 6.6 to 7.8 between 24 and 72 h after the second surgery. The survival rate was significantly increased with low and high doses of dexrazoxane (ranges, 57-52% and 66-60%, respectively). Total neurological scores with 32 and 128 mg/kg of dexrazoxane (ranges, 4.5-5.4 and 3.3-4.0, respectively) were significantly lower (P<0.05) than its corresponding solvent. Dexrazoxane administration also avoided hypolocomotion and motor incoordination produced by SCAS. None of three known putative neuroprotective agents tested in this study reduced the mortality and/or consistently diminished neurological deficits. We conclude that dexrazoxane has very important neuroprotective properties and that our scale is useful to quantify the degree of neurological impairment after brain ischemia. © 2003. Wiley Liss, Inc.
Original languageAmerican English
Pages (from-to)294-302
Number of pages263
JournalDrug Development Research
DOIs
StatePublished - 1 Dec 2003

Fingerprint

Dexrazoxane
Common Carotid Artery
arteries
mice
animals
ischemia
mortality
brain
vehicles
Brain Ischemia
disabilities
impairment
Survival Rate
death
surgery
grade
Nimodipine
Deferoxamine
Mortality
examination

Cite this

@article{0e4a566a44a94a1691c9526b495f5750,
title = "Outstanding Neuroprotective Efficacy of Dexrazoxane in Mice Subjected to Sequential Common Carotid Artery Sectioning",
abstract = "We evaluated the efficacy of the iron chelator, dexrazoxane, to reduce the neurological alterations and mortality produced by sequential common carotid artery sectioning (SCAS) in mice. Deferoxamine (32 and 128 mg/kg), dexrazoxane (32 and 128 mg/kg), dizolcipine (0.8 and 3.2 mg/kg), or nimodipine (0.4 and 1.6 mg/kg) were injected ip 15 min after the second artery sectioning. Animals were evaluated at 24, 48, and 72 h after compound or vehicle injection using three procedures: neurological examination, spontaneous locomotor activity, and motor coordination. Based on neurological evaluation, we designed and used a disability status scale (NDSS) to determine the degree of functional incapacity after brain ischemia for each animal. The scale comprises 10 progressive grades or steps beyond 0 (normal), extending to status 10 (death due to SCAS). In this scale, the higher the number, the greater is the neurological dysfunction. For the vehicle-treated animals, the survival rate ranged from 41 to 30{\%} and the neurological scores ranged from 6.6 to 7.8 between 24 and 72 h after the second surgery. The survival rate was significantly increased with low and high doses of dexrazoxane (ranges, 57-52{\%} and 66-60{\%}, respectively). Total neurological scores with 32 and 128 mg/kg of dexrazoxane (ranges, 4.5-5.4 and 3.3-4.0, respectively) were significantly lower (P<0.05) than its corresponding solvent. Dexrazoxane administration also avoided hypolocomotion and motor incoordination produced by SCAS. None of three known putative neuroprotective agents tested in this study reduced the mortality and/or consistently diminished neurological deficits. We conclude that dexrazoxane has very important neuroprotective properties and that our scale is useful to quantify the degree of neurological impairment after brain ischemia. {\circledC} 2003. Wiley Liss, Inc.",
author = "Rodolfo Rodriguez and Jacinto Santiago-Mejia and Monica Fuentes-Vargas and {Ramirez San-Juan}, Eduardo",
year = "2003",
month = "12",
day = "1",
doi = "10.1002/ddr.10330",
language = "American English",
pages = "294--302",
journal = "Drug Development Research",
issn = "0272-4391",
publisher = "John Wiley and Sons Inc.",

}

Outstanding Neuroprotective Efficacy of Dexrazoxane in Mice Subjected to Sequential Common Carotid Artery Sectioning. / Rodriguez, Rodolfo; Santiago-Mejia, Jacinto; Fuentes-Vargas, Monica; Ramirez San-Juan, Eduardo.

In: Drug Development Research, 01.12.2003, p. 294-302.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Outstanding Neuroprotective Efficacy of Dexrazoxane in Mice Subjected to Sequential Common Carotid Artery Sectioning

AU - Rodriguez, Rodolfo

AU - Santiago-Mejia, Jacinto

AU - Fuentes-Vargas, Monica

AU - Ramirez San-Juan, Eduardo

PY - 2003/12/1

Y1 - 2003/12/1

N2 - We evaluated the efficacy of the iron chelator, dexrazoxane, to reduce the neurological alterations and mortality produced by sequential common carotid artery sectioning (SCAS) in mice. Deferoxamine (32 and 128 mg/kg), dexrazoxane (32 and 128 mg/kg), dizolcipine (0.8 and 3.2 mg/kg), or nimodipine (0.4 and 1.6 mg/kg) were injected ip 15 min after the second artery sectioning. Animals were evaluated at 24, 48, and 72 h after compound or vehicle injection using three procedures: neurological examination, spontaneous locomotor activity, and motor coordination. Based on neurological evaluation, we designed and used a disability status scale (NDSS) to determine the degree of functional incapacity after brain ischemia for each animal. The scale comprises 10 progressive grades or steps beyond 0 (normal), extending to status 10 (death due to SCAS). In this scale, the higher the number, the greater is the neurological dysfunction. For the vehicle-treated animals, the survival rate ranged from 41 to 30% and the neurological scores ranged from 6.6 to 7.8 between 24 and 72 h after the second surgery. The survival rate was significantly increased with low and high doses of dexrazoxane (ranges, 57-52% and 66-60%, respectively). Total neurological scores with 32 and 128 mg/kg of dexrazoxane (ranges, 4.5-5.4 and 3.3-4.0, respectively) were significantly lower (P<0.05) than its corresponding solvent. Dexrazoxane administration also avoided hypolocomotion and motor incoordination produced by SCAS. None of three known putative neuroprotective agents tested in this study reduced the mortality and/or consistently diminished neurological deficits. We conclude that dexrazoxane has very important neuroprotective properties and that our scale is useful to quantify the degree of neurological impairment after brain ischemia. © 2003. Wiley Liss, Inc.

AB - We evaluated the efficacy of the iron chelator, dexrazoxane, to reduce the neurological alterations and mortality produced by sequential common carotid artery sectioning (SCAS) in mice. Deferoxamine (32 and 128 mg/kg), dexrazoxane (32 and 128 mg/kg), dizolcipine (0.8 and 3.2 mg/kg), or nimodipine (0.4 and 1.6 mg/kg) were injected ip 15 min after the second artery sectioning. Animals were evaluated at 24, 48, and 72 h after compound or vehicle injection using three procedures: neurological examination, spontaneous locomotor activity, and motor coordination. Based on neurological evaluation, we designed and used a disability status scale (NDSS) to determine the degree of functional incapacity after brain ischemia for each animal. The scale comprises 10 progressive grades or steps beyond 0 (normal), extending to status 10 (death due to SCAS). In this scale, the higher the number, the greater is the neurological dysfunction. For the vehicle-treated animals, the survival rate ranged from 41 to 30% and the neurological scores ranged from 6.6 to 7.8 between 24 and 72 h after the second surgery. The survival rate was significantly increased with low and high doses of dexrazoxane (ranges, 57-52% and 66-60%, respectively). Total neurological scores with 32 and 128 mg/kg of dexrazoxane (ranges, 4.5-5.4 and 3.3-4.0, respectively) were significantly lower (P<0.05) than its corresponding solvent. Dexrazoxane administration also avoided hypolocomotion and motor incoordination produced by SCAS. None of three known putative neuroprotective agents tested in this study reduced the mortality and/or consistently diminished neurological deficits. We conclude that dexrazoxane has very important neuroprotective properties and that our scale is useful to quantify the degree of neurological impairment after brain ischemia. © 2003. Wiley Liss, Inc.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=0344443761&origin=inward

UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=0344443761&origin=inward

U2 - 10.1002/ddr.10330

DO - 10.1002/ddr.10330

M3 - Article

SP - 294

EP - 302

JO - Drug Development Research

JF - Drug Development Research

SN - 0272-4391

ER -