title: Chronic Alcohol Intoxication and Cortical Ischemia: Study of Their Comorbidity and the Protective Effects of Minocycline.
abstract: Chronic alcohol intoxication (CAI) increases both morbidity and mortality of stroke patients. Despite the high prevalence of CAI and ischemic stroke, studies addressing their comorbidity and/or protective alternatives remain scarce. Thus, the influence of CAI on both stroke outcome and minocycline treatment (recognized for its neuroprotective effect) was investigated. Female Wistar rats (35 days old) were treated with water or ethanol (6.5 g/kg/day, 22.5% w/v) for 55 days. Then, focal ischemia was induced by endothelin-1 in the motor cortex. Two hours later, four doses of 50 mg/kg of minocycline every 12 hours followed by five doses of 25 mg/kg every 24 hours were administered. Behavioral performance (open field and rotarod tests) and immunohistochemical (cellular density, neuronal death, and astrocytic activation) and biochemical (lipid peroxidation and nitrite levels) analyses were performed. CAI increased motor disruption, nitrite and lipid peroxidation levels, and neuronal loss caused by ischemia, whereas it reduced the astrogliosis. Minocycline was effective in preventing the motor and tissue damage caused by stroke. However, these effects were attenuated when CAI preceded stroke. Our data suggest that CAI beginning in adolescence contributes to a worse outcome in ischemic stroke survivors and reduces the benefits of minocycline, possibly requiring adjustments in therapy.
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Biological Sciences, Federal University of Pará, 66075-110 Belém, PA, Brazil; Laboratory of Pharmacology of Inflammation and Behavior, Institute of Health Sciences, Federal University of Pará, 66075-110 Belém, PA, Brazil.
authors.forename: Enéas Andrade
authors.identifier: 0000-0002-6186-9581
authors.initials: EA
authors.lastname: Fontes-Júnior
authors.affiliation: Laboratory of Pharmacology of Inflammation and Behavior, Institute of Health Sciences, Federal University of Pará, 66075-110 Belém, PA, Brazil.
authors.forename: Cristiane Socorro Ferraz
authors.identifier: 0000-0003-4493-7375
authors.initials: CS
authors.lastname: Maia
authors.affiliation: Laboratory of Pharmacology of Inflammation and Behavior, Institute of Health Sciences, Federal University of Pará, 66075-110 Belém, PA, Brazil.
authors.forename: Luanna Melo Pereira
authors.initials: LM
authors.lastname: Fernandes
authors.affiliation: Laboratory of Experimental Neuroprotection and Neurodegeneration, Institute of Biological Sciences, Federal University of Pará, 66075-110 Belém, PA, Brazil.
authors.forename: Walace
authors.initials: W
authors.lastname: Gomes-Leal
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Biological Sciences, Federal University of Pará, 66075-110 Belém, PA, Brazil.
authors.forename: Allan
authors.identifier: 0000-0003-3432-011X
authors.initials: A
authors.lastname: Costa-Malaquias
authors.affiliation: Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, 66075-110 Belém, PA, Brazil.
authors.forename: Rafael Rodrigues
authors.initials: RR
authors.lastname: Lima
authors.affiliation: Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Rui Daniel
authors.initials: RD
authors.lastname: Prediger
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Biological Sciences, Federal University of Pará, 66075-110 Belém, PA, Brazil.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Crespo-López
mesh_terms: D000435:Alcoholic Intoxication / Q000150:complications / Q000188:drug therapy*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000633:toxicity; D005260:Female; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D009044:Motor Cortex / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019332:Endothelin-1; D018696:Neuroprotective Agents; D009573:Nitrites; D008911:Minocycline