title: Intranasal guanosine administration presents a wide therapeutic time window to reduce brain damage induced by permanent ischemia in rats.
abstract: In addition to its intracellular roles, the nucleoside guanosine (GUO) also has extracellular effects that identify it as a putative neuromodulator signaling molecule in the central nervous system. Indeed, GUO can modulate glutamatergic neurotransmission, and it can promote neuroprotective effects in animal models involving glutamate neurotoxicity, which is the case in brain ischemia. In the present study, we aimed to investigate a new in vivo GUO administration route (intranasal, IN) to determine putative improvement of GUO neuroprotective effects against an experimental model of permanent focal cerebral ischemia. Initially, we demonstrated that IN [(3)H] GUO administration reached the brain in a dose-dependent and saturable pattern in as few as 5 min, presenting a higher cerebrospinal GUO level compared with systemic administration. IN GUO treatment started immediately or even 3 h after ischemia onset prevented behavior impairment. The behavior recovery was not correlated to decreased brain infarct volume, but it was correlated to reduced mitochondrial dysfunction in the penumbra area. Therefore, we showed that the IN route is an efficient way to promptly deliver GUO to the CNS and that IN GUO treatment prevented behavioral and brain impairment caused by ischemia in a therapeutically wide time window.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, Santana, 90035-003, Porto Alegre, RS, Brazil. denibaramos@yahoo.com.br.
authors.forename: Denise Barbosa
authors.initials: DB
authors.lastname: Ramos
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, Santana, 90035-003, Porto Alegre, RS, Brazil. mullergabriel94@gmail.com.
authors.forename: Gabriel Cardozo
authors.initials: GC
authors.lastname: Muller
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, Santana, 90035-003, Porto Alegre, RS, Brazil. guilhermebmrocha@gmail.com.
authors.forename: Guilherme Botter Maio
authors.initials: GB
authors.lastname: Rocha
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, Santana, 90035-003, Porto Alegre, RS, Brazil. hirata.dellavia@ufrgs.br.
authors.forename: Gustavo Hirata
authors.initials: GH
authors.lastname: Dellavia
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, Santana, 90035-003, Porto Alegre, RS, Brazil. almeida_rf@yahoo.com.br.
authors.forename: Roberto Farina
authors.initials: RF
authors.lastname: Almeida
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, Santana, 90035-003, Porto Alegre, RS, Brazil. leticiapettenuzzo@gmail.com.
authors.forename: Leticia Ferreira
authors.initials: LF
authors.lastname: Pettenuzzo
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, Santana, 90035-003, Porto Alegre, RS, Brazil. dasamanta@yahoo.com.br.
authors.forename: Samanta Oliveira
authors.initials: SO
authors.lastname: Loureiro
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, Santana, 90035-003, Porto Alegre, RS, Brazil. gihansel@gmail.com.
authors.forename: Gisele
authors.initials: G
authors.lastname: Hansel
authors.affiliation: Instituto Federal de Educação, Ciência e Tecnologia do Rio Grande do Sul, IFRS, Campus Porto Alegre, Rua Ramiro Barcelos, 2777, Santana, 90035-007, Porto Alegre, RS, Brazil. angelo.horn@poa.ifrs.edu.br.
authors.forename: Ângelo Cássio Magalhães
authors.initials: ÂC
authors.lastname: Horn
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, Santana, 90035-003, Porto Alegre, RS, Brazil. diogo@ufrgs.br.
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, Santana, 90035-003, Porto Alegre, RS, Brazil. ganzellam@gmail.com.|Now at: Neurobiology Department, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077, Göttingen, Germany. ganzellam@gmail.com.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ganzella
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000188:drug therapy* / Q000523:psychology; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D006151:Guanosine / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000188:drug therapy* / Q000523:psychology
chemical_list: D018696:Neuroprotective Agents; D006151:Guanosine
keywords: Guanosine; Intranasal; Ischemia; Neuroprotection; Purines