Articles are published in international journals
Doctoral students Pamella Azevedo and Felipe Odorcyk developed two researches with the latest technology and high standard of results related to neonatal hypoxia-ischemia (HI), which were published in international magazines. Developed in collaboration with UFRGS and the InsCer Pre-Clinical Research Center, the research addresses different aspects of the same disease.
Neonatal hypoxia-ischemia is a major cause of morbidity and mortality in newborns. This disease is caused by a decrease or interruption in blood flow to the fetus that can be caused by problems during delivery. The reduction in brain blood flow causes death of neurons and lasting damage to the nervous system, which can cause, for example, cerebral palsy.
Events of hypoxia and cerebral ischemia in newborns are capable of triggering important brain changes, leading to the development of permanent neurological diseases, which can range from mild cognitive and motor disabilities to cerebral palsy. These brain changes include abnormalities in the metabolism of the brain that may be related to the severity of the insult.
In the study conducted by Pamella Azevedo, and published in the international journal “Neurobiology of Learning and Memory”, changes in brain metabolism were investigated in an experimental model of neonatal HI, by examining positron emission microtomography (microPET) ) which, associated with a radiopharmaceutical analogous to the glucose molecule (18F-FDG), was able to measure the consumption of glucose by the brain cells of animals.
The results of the research showed that hypoxia-ischemia was able to decrease the consumption of cerebral glucose for most animals, and this change was accompanied by deficits in spatial memory. However, part of the animals that did not show changes in metabolism also showed significant memory impairment. This dissociation between metabolism and cognitive performance indicated changes in brain function even without detectable changes in microPET images.
Only with the construction of a cerebral metabolic network, based on the findings of the microPET-FDG, were brain alterations identified, even without the impairment of metabolism, demonstrating, for the first time, that long-term changes in the cerebral metabolic network cause memory impairment in animals submitted to neonatal hypoxia-ischemia.
“Briefly, the work addresses brain complexity: where there is sometimes no macroscopic brain injury, detectable through a resonance exam, for example, it is necessary to use other technologies and research approaches. In this study, it was only possible to identify the injury of some animals when we saw a change in the cerebral metabolic network, where the brain regions were not in sync, which influenced the proper brain functioning ”, says Azevedo.
The article is available here .
Previous studies have already shown that, when subjected to the same injury, caused by HI, younger rats suffer significantly less damage than older animals. This effect is even more striking when the first days of life are analyzed.
The research, conducted by Odorcyk and published in the international journal “Experimental Neurology”, demonstrated that the same model of HI that causes great learning and tissue damage in the brain when induced in mice with seven days of life does not cause detectable damage when it occurs at three days of life. This means that, in a few days, the brain's susceptibility to HI changes dramatically, and suggests that the younger brain has intrinsic protection.
Therefore, in order to improve understanding of the pathology of HI and seek new therapeutic targets to treat it, the study investigated the biological causes behind this greater resilience of the younger brain.
“From a wide repertoire of techniques, such as microPET-FDG neuroimaging in partnership with the PUCRS Brain Institute, we demonstrate that the intrinsic protection of the younger brain is due to differences in brain metabolism, especially due to the greater use of ketone bodies by the still immature brain. These results suggest that brain metabolism is a very promising therapeutic target for the treatment of neonatal hypoxia-ischemia ”, concludes Odorcyk.
The article is available here .
InsCer's Pre-Clinical Research Center (CPPC) is a cutting-edge unit that houses state-of-the-art equipment for basic research. The pre-clinical molecular imaging system allows in vivo imaging through positron emission microtomography (microPET) and computerized microtomography (microCT) in small animals, such as rats and mice. Like PET / CT, microPET / CT combines two imaging modalities, making possible studies that correlate cellular / molecular function with anatomical structure. In addition, CPPC also has a gamma counter, essential equipment for studies on biodistribution and kinetic modeling in microPET. Thus, pharmacokinetic and pharmacodynamic characteristics of a molecule under study can be determined in vivo.
