title: Minocycline mitigates motor impairments and cortical neuronal loss induced by focal ischemia in rats chronically exposed to ethanol during adolescence.
abstract: Ethanol is an important risk factor for the occurrence of cerebral ischemia contributing to poor prognosis and inefficacy of drug treatments for stroke-related symptoms. Females have a higher lifetime risk for stroke than males. Moreover, female gender has been associated with increased ethanol consumption during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence may potentiate the motor impairments and cortical damage induced by focal ischemia in female rats. We also addressed whether these effects can be mitigated by minocycline, which has been shown to be neuroprotective against different insults in the CNS. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) for 55 days by gavage. Focal ischemia was induced by microinjections of endothelin-1 (ET-1) into the motor cortex. Animals of both groups were treated daily with minocycline (25-50 mg/kg, i.p.) or sterile saline (i.p.) for 5 days, and motor function was assessed using open field, inclined plane and rotarod tests. Chronic ethanol exposure exacerbated locomotor activity and motor coordination impairments induced by focal ischemia in rats. Moreover, histological analysis revealed that microinjections of ET-1 induced pyramidal neuron loss and microglial activation in the motor cortex. Minocycline reversed the observed motor impairments, microglial activation and pyramidal neuron loss in the motor cortex of ischemic rats even in those exposed to ethanol. These results suggest that minocycline induces neuroprotection and functional recovery in ischemic female rats intoxicated with ethanol during adolescence. Furthermore, the mechanism underlying this protective effect may be related to the modulation of neuroinflammation.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil.
authors.forename: Gedeão Batista
authors.initials: GB
authors.lastname: Oliveira
authors.affiliation: Programa de Pós-graduação em Neurociências e Biologia Celular, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil.
authors.forename: Enéas de Andrade
authors.initials: Ede A
authors.lastname: Fontes
authors.affiliation: Laboratório de Farmacologia da Inflamação e do Comportamento, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil.
authors.forename: Sabrina
authors.initials: S
authors.lastname: de Carvalho
authors.affiliation: Laboratório de Farmacologia da Inflamação e do Comportamento, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil.
authors.forename: Josiane Batista
authors.initials: JB
authors.lastname: da Silva
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil; Laboratório de Farmacologia da Inflamação e do Comportamento, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil.
authors.forename: Luanna Melo Pereira
authors.initials: LM
authors.lastname: Fernandes
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil.
authors.forename: Maria Cristina Souza Pereira
authors.initials: MC
authors.lastname: Oliveira
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900 Florianópolis, SC, Brazil.
authors.forename: Rui Daniel
authors.initials: RD
authors.lastname: Prediger
authors.affiliation: Laboratório de Neuroproteção e Neurorregeneração Experimental do Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil.
authors.forename: Walace
authors.initials: W
authors.lastname: Gomes-Leal
authors.affiliation: Laboratório de Neuroproteção e Neurorregeneração Experimental do Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil.
authors.forename: Rafael Rodrigues
authors.initials: RR
authors.lastname: Lima
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil; Programa de Pós-graduação em Neurociências e Biologia Celular, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil; Laboratório de Farmacologia da Inflamação e do Comportamento, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil. Electronic address: crismaia@ufpa.br.
authors.forename: Cristiane Socorro Ferraz
authors.initials: CS
authors.lastname: Maia
mesh_terms: D019973:Alcohol-Related Disorders / Q000150:complications; D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D004195:Disease Models, Animal; D019332:Endothelin-1; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D008911:Minocycline / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009044:Motor Cortex / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects
chemical_list: D002492:Central Nervous System Depressants; D019332:Endothelin-1; D018696:Neuroprotective Agents; D000431:Ethanol; D008911:Minocycline
keywords: Adolescence; Cerebral ischemia; Ethanol; Minocycline; Motor Cortex; Motor deficits; Neuroinflammation