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.