title: Effects of chronic guanosine treatment on hippocampal damage and cognitive impairment of rats submitted to chronic cerebral hypoperfusion.
abstract: Chronic cerebral hypoperfusion contributes to a cognitive decline related to brain disorders. Its experimental model in rats is a permanent bilateral common carotid artery occlusion (2VO). Overstimulation of the glutamatergic system excitotoxicity due to brain energetic disturbance in 2VO animals seems to play a pivotal role as a mechanism of cerebral damage. The nucleoside guanosine (GUO) exerts extracellular effects including antagonism of glutamatergic activity. Accordingly, our group demonstrated several neuroprotective effects of GUO against glutamatergic excitotoxicity. Therefore, in this study, we evaluated a chronic GUO treatment effects in rats submitted to 2VO. We evaluated the animals performance in the Morris water maze and hippocampal damage by neurons and astrocytes immunohistochemistry. In addition, we investigated the cerebrospinal fluid (CSF) brain derived neurotrophic factor (BDNF) and serum S100B levels. Additionally, the purine CSF and plasma levels were determined. GUO treatment did not prevent the cognitive impairment promoted by 2VO. However, none of the 2VO animals treated with GUO showed differences in the hippocampal regions compared to control, while 20% of 2VO rats not treated with GUO presented loss of pyramidal neurons and increased glial labeling cells in CA1 hippocampal region. In addition, we did not observe differences in CSF BDNF nor serum S100B levels among the groups. Of note, both the 2VO surgery and GUO treatment changed the purine CSF and plasma profile. In conclusion, GUO treatment did not prevent the cognitive impairment observed in 2VO animals, but our data suggest that GUO could be neuroprotective against hippocampal damage induced by 2VO.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcellos, 2600, anexo, Santana, Porto Alegre, RS 90035-003, Brazil. ganzellam@hotmail.com
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ganzella
authors.forename: Enderson Dias Alves
authors.initials: ED
authors.lastname: de Oliveira
authors.forename: Daniel Diniz
authors.initials: DD
authors.lastname: Comassetto
authors.forename: Fernanda
authors.initials: F
authors.lastname: Cechetti
authors.forename: Victor Hermes
authors.initials: VH
authors.lastname: Cereser
authors.forename: Júlia Dubois
authors.initials: JD
authors.lastname: Moreira
authors.forename: Gisele
authors.initials: G
authors.lastname: Hansel
authors.forename: Roberto Farina
authors.initials: RF
authors.lastname: Almeida
authors.forename: Denise Barbosa
authors.initials: DB
authors.lastname: Ramos
authors.forename: Yanier Nuñes
authors.initials: YN
authors.lastname: Figueredo
authors.forename: Debora Guerini
authors.initials: DG
authors.lastname: Souza
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Oses
authors.forename: Paulo Valdeci
authors.initials: PV
authors.lastname: Worm
authors.forename: Matilde
authors.initials: M
authors.lastname: Achaval
authors.forename: Carlos Alexandre
authors.initials: CA
authors.lastname: Netto
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006151:Guanosine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011687:Purines / Q000097:blood / Q000134:cerebrospinal fluid; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; D011687:Purines; D006151:Guanosine