Efeitos neurohistológicos e comportamentais da isquemia cerebral global e transitória em camundongos

Abstract

Transient global cerebral ischemia (TGCI), leads to the reduction of oxygen and glucose to the brain tissues, causing cell death and neurodegeneration in susceptible regions such as the hippocampus, especially the CA1 subfield, reticular nucleus of the thalamus, cortex and striatum. Neurodegeneration has been associated with behavioral/emotional, cognitive and motor deficits. The effects of TGCI are well characterized in rats, but in mice, there are few studies reporting on these effects. Moreover, the results published in mice are often inconsistent and incomplete, which complicates interpretations and, the choice of the best parameters for evaluating the neuroprotective effects of drugs. Therefore the objective of this study was to characterize the time course of behavioral changes and hippocampal neurodegeneration after TGCI in mice. For this, adult, male albino Swiss, mice, weighing 30-40 g were used. Initially we evaluated the degree of hippocampal neurodegeneration by Nissl staining, as a function of TCGI duration, i.e. 12, 17 or 25 minutes. Based on the presence of effective neurodegeneration and high survival rate, the time of 17min was chosen for the next experiments, in which the behavioral and neurodegenerative effects of TGCI with different chronicities were examined. Mice were subject to TGCI and 7, 14 or 28 days later they were evaluated for learning and memory deficit (Morris water maze, MWM), locomotor changes (open-field, OP), anxiety like-behavior (elevated plus maze, EPM), and hippocampal damage (Nissl and FluoroJade-C staning). Neurodegeneration was detected in the hippocampal subfields CA1, CA2, CA3 and CA4 whatever the chronicity of TGCI. FJ C-positive cells were present up to 14 days of TGCI, indicating this is the post-ischemic period during which those neurons destined to die will do it.. Cognitive deficits, characterized by an increased latency to find the plataform and a lower residence time in the correct quadrant were observed 7 and 14 days after TGCI. Avoidance behaviors of the open arms of the EPM were recorded 7 and 14 days after TGCI, featuring anxiogenic-like behavior of the animals. In OP we observed decreased time spent and number of entry in the "center" just for the group 28 days after TGCI. In conclusion, TGCI 17 min caused robust hippocampal neurodegeneration and emotional and cognitive deficits, that varied from time-dependent manner after TGCI.