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
Y1 - 2003/12
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.
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.
KW - Brain ischemia
KW - Deferoxamine
KW - Dexrazoxane
KW - Dizolcipine
KW - Mice
KW - Nimodipine
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=0344443761&partnerID=8YFLogxK
U2 - 10.1002/ddr.10330
DO - 10.1002/ddr.10330
M3 - Artículo
SN - 0272-4391
VL - 60
SP - 294
EP - 302
JO - Drug Development Research
JF - Drug Development Research
IS - 4
ER -