Caracterização longitudinal in vivo do metabolismo cerebral no modelo experimental de hipóxia isquemia neonatal

Abstract

Hypoxia-ischemic encephalopathy (HI) is one of the leading causes of mortality and neurological morbidity on term and preterm newborns. Neonatal HI can lead to several degrees of neurological impairment in affected neonates, such as cerebral palsy, autism, and epilepsy. Despite considerable in neonatal care advances, the clinical management of children is limited to support measures are developed to prevent or halt brain damaging machanisms new technologies aimed at preventing or disrupting brain injury mechanisms. Damage severity is related to factors, such as nature and duration of the insult and the genetic background, for example. Due to the clinical significance and the socioeconomic impact caused by this pathology, new strategies have been studied. Noninvasive imaging systems could elucidate the mechanisms of HI injury and contribute to the research for effective therapy strategies. Therefore the aim of the present study was to verify in vivo, longitudinally, possible alterations in the cerebral glucose metabolism in rats subjected to the neonatal HI model, by microPET scanning. The obtained uptake was correlated the results of the functional imaging with the anatomical, motor and cognitive parameters. Male Wistar rats at postnatal day 7 (P7) were subjected to an HI model by permanent occlusion of right common carotid artery and placed in hypoxia environment for 1 h. MicroPET associated with [18]fluordeoxyglucose (18F-FDG) was used to investigate the cerebral metabolism in vivo of rats at 8, 10, 15, 36 and 60 days of age. Aditionally, the spatial orientation memory was evaluated through the Morris Water Maze (MWM) and later, the brain volume was analyzed by histological evaluations. Our results demonstrated transient hypometabolism in the cortex, hippocampus, and striatum of the hemisphere contralateral to the hypoxic-ischemic lesion at 10 and 15 days of life. In the right hemisphere, ipsilateral to the lesion, hypometabolism was observed only at 36 and 60 days of life of hypoxic-ischemic animals for the most of the evaluated brain regions. In addition, neonatal HI altered the conformation of the cerebral metabolic network in adolescent / adult animals previously submitted to the model when compared to control animals. Finally, cognitive impairments and loss of brain volume in HI animals were correlated with changes in brain metabolism in adulthood. Thus, we conclude that microPET-FDG was effective in the detection and quantification of early and late metabolic abnormalities, correlating cerebral metabolism with brain lesions and cognitive deficits in neonatal HI.