Guanosine Protects Against Cortical Focal Ischemia. Involvement of Inflammatory Response.
Stroke is the major cause of death and the most frequent cause of disability in the adult population worldwide. Guanosine plays an important neuroprotective role in several cerebral ischemic models and is involved in the modulation of oxidative responses and glutamatergic parameters. Because the excessive reactive oxygen species produced during an ischemic event can trigger an inflammatory response, the purpose of this study was to evaluate the hypothesis that guanosine is neuroprotective against focal cerebral ischemia, inhibits microglia/macrophages activation, and mediates an inflammatory response ameliorating the neural damage. Permanent focal cerebral ischemia was induced in adult rats, and guanosine was administered immediately, 1, 3, and 6 h after surgery. Twenty-four hours after ischemia, the asymmetry scores were evaluated by the cylinder test; neuronal damage was evaluated by Fluoro-Jade C (FJC) staining and propidium iodide (PI) incorporation; microglia and immune cells were evaluated by anti-Iba-1 antibody; and inflammatory parameters such as interleukins (IL): IL-1, IL-6, IL-10; tumor necrosis factors alpha (TNF-α); and interferon-gamma (INF-γ) were evaluated in the brain tissue and cerebrospinal fluid. The ischemic event increased the levels of Iba-1-positive cells and pro-inflammatory cytokines and decreased IL-10 levels (an anti-inflammatory cytokine) in the lesion periphery. The guanosine treatment attenuated the changes in these inflammatory parameters and also reduced the infarct volume, PI incorporation, and number of FJC-positive cells, improving the functional recovery. Thus, guanosine may have been a promising therapeutic agent for the treatment of ischemic brain injury by reduction of inflammatory process triggered in an ischemic event.
Department of Biochemistry, Postgraduate Program in Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600 - Anexo, Santa Cecília, 90035-003, Porto Alegre, RS, Brazil. gihansel@gmail.com.
Gisele
G
Hansel
Department of Biochemistry, Postgraduate Program in Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600 - Anexo, Santa Cecília, 90035-003, Porto Alegre, RS, Brazil.
André Comiran
AC
Tonon
Department of Biochemistry, Postgraduate Program in Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600 - Anexo, Santa Cecília, 90035-003, Porto Alegre, RS, Brazil.
Felipe Lhywinskh
FL
Guella
Department of Biochemistry, Postgraduate Program in Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600 - Anexo, Santa Cecília, 90035-003, Porto Alegre, RS, Brazil.
Letícia Ferreira
LF
Pettenuzzo
Postgraduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil.
Thiago
T
Duarte
Health Sciences Center, Lutheran University of Brazil (ULBRA) - Campus Santa Maria, Santa Maria, RS, Brazil.
Marta Maria Medeiros Frescura
MMMF
Duarte
Postgraduate Program in Health and Behavior, Health and Biological Sciences Center, Catholic University of Pelotas (UCPel), Pelotas, RS, Brazil.
Jean Pierre
JP
Oses
Department of Compared Histophysiologies and Morphologic Science, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Matilde
M
Achaval
Department of Biochemistry, Postgraduate Program in Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600 - Anexo, Santa Cecília, 90035-003, Porto Alegre, RS, Brazil.
Diogo Onofre
DO
Souza
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006151:Guanosine / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D006151:Guanosine
Cerebral ischemia; Cytokines; Guanosine; Microglia; Neuroinflammation; Neuroprotection