Avaliação do metabolismo cerebral de glicose in vivo e da memória espacial de ratos adultos submetidos a hipóxia-isquemia neonatal

Abstract

Perinatal hypoxia-ischemia (HI) is one of the most common causes of infant mortality and morbidity. Statistical studies suggest that the mortality rate of newborns asphyxiated in the neonatal period is 20 to 50%, and more than 25% of the survivors present permanent neuropsychological disabilities, such as mental retardation, cerebral palsy, epilepsy and learning disabilities. The experimental model of neonatal HI, proposed by Rice et al., is the most accepted in the scientific community, mimicking several aspects of pathophysiology in the human condition. In this animal model, brain damage is achieved through the association of permanent occlusion of the right common carotid artery and subsequent exposure to a hypoxic environment (8% O2). The lesion is limited to the cerebral hemisphere ipsilateral to the occlusion and, similar to the clinical reality, there is great variability of the cerebral lesion. These observations stimulate experimental research aimed at understanding the development of brain injury and, a posteriori, maintaining the integrity of the CNS from therapeutic interventions. Thus, the objective of this study was to evaluate the brain injury of adult rats previously submitted to neonatal HI, through the in vivo analysis of cerebral glucose metabolism, and to correlate these findings with the cognitive performance of these animals. For this study, a total of 22 male Wistar rats with 7 days of life were used. At 7 days of life, Wistar rats were submitted to the neonatal HI model. At 60 days of life, 53 days after the induction of HI, these animals were submitted to imaging examinations by microPET (positron emission microtomography) and the 18F-FDG radiopharmaceutical (18F- fluorordesoxyglucose) for analysis of cerebral glucose metabolism. Subsequently, the animals were evaluated for spatial memory through the Morris Water Maze test. Through microPET-FDG scanning, we observed a significant hemispheric cerebral hypometabolism ipsilateral to carotid occlusion in hypoxic-ischemic adult animals with possible detectable lesional area in the functional image. In addition, we have shown that there is an inversely proportional correlation between altered brain metabolism and spatial memory deficit of adult rats previously submitted to the neonatal HI model.