title: The potential therapeutic effect of guanosine after cortical focal ischemia in rats.
abstract: OBJECTIVE
  Stroke is a devastating disease. Both excitotoxicity and oxidative stress play important roles in ischemic brain injury, along with harmful impacts on ischemic cerebral tissue. As guanosine plays an important neuroprotective role in the central nervous system, the purpose of this study was to evaluate the neuroprotective effects of guanosine and putative cerebral events following the onset of permanent focal cerebral ischemia.
  
  
  METHODS
  Permanent focal cerebral ischemia was induced in rats by thermocoagulation. Guanosine was administered immediately, 1 h, 3 h and 6 h after surgery. Behavioral performance was evaluated by cylinder testing for a period of 15 days after surgery. Brain oxidative stress parameters, including levels of ROS/RNS, lipid peroxidation, antioxidant non-enzymatic levels (GSH, vitamin C) and enzymatic parameters (SOD expression and activity and CAT activity), as well as glutamatergic parameters (EAAC1, GLAST and GLT1, glutamine synthetase) were analyzed.
  
  
  RESULTS
  After 24 h, ischemic injury resulted in impaired function of the forelimb, caused brain infarct and increased lipid peroxidation. Treatment with guanosine restored these parameters. Oxidative stress markers were affected by ischemic insult, demonstrated by increased ROS/RNS levels, increased SOD expression with reduced SOD activity and decreased non-enzymatic (GSH and vitamin C) antioxidant defenses. Guanosine prevented increased ROS/RNS levels, decreased SOD activity, further increased SOD expression, increased CAT activity and restored vitamin C levels. Ischemia also affected glutamatergic parameters, illustrated by increased EAAC1 levels and decreased GLT1 levels; guanosine reversed the decreased GLT1 levels and did not affect the EAAC1 levels.
  
  
  CONCLUSIONS
  The effects of brain ischemia were strongly attenuated by guanosine administration. The cellular mechanisms involved in redox and glutamatergic homeostasis, which were both affected by the ischemic insult, were also modulated by guanosine. These observations reveal that guanosine may represent a potential therapeutic agent in cerebral ischemia by preventing oxidative stress and excitotoxicity.
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas-Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Gisele
authors.initials: G
authors.lastname: Hansel
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas-Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Denise Barbosa
authors.initials: DB
authors.lastname: Ramos
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas-Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Camila Aguilar
authors.initials: CA
authors.lastname: Delgado
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas-Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Débora Guerini
authors.initials: DG
authors.lastname: Souza
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas-Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Roberto Farina
authors.initials: RF
authors.lastname: Almeida
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas-Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Luis Valmor
authors.initials: LV
authors.lastname: Portela
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas-Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Quincozes-Santos
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas-Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology*; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004564:Electrocoagulation / Q000009:adverse effects; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005552:Forelimb / Q000187:drug effects / Q000503:physiopathology; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006151:Guanosine / Q000008:administration & dosage / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C493398:Slc1a1 protein, rat; D006151:Guanosine; D009569:Nitric Oxide; D002374:Catalase; D013482:Superoxide Dismutase; D005974:Glutamate-Ammonia Ligase; D005978:Glutathione; D001205:Ascorbic Acid