Differential glucose and beta-hydroxybutyrate metabolism confers an intrinsic neuroprotection to the immature brain in a rat model of neonatal hypoxia ischemia
| Autor: | A.P. Martini, Gianina Teribele Venturin, Eduardo Farias Sanches, L E Duran-Carabali, Carlos Alexandre Netto, Eduardo R. Zimmer, Felipe Kawa Odorcyk, Débora Santos Rocha, L.C. Kucharski, Samuel Greggio, J.C. da Costa |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Ischemia Neuroprotection Lesion 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience In vivo Internal medicine medicine Animals Rats Wistar medicine.diagnostic_test 3-Hydroxybutyric Acid business.industry Histology Metabolism medicine.disease Rats Disease Models Animal 030104 developmental biology Endocrinology Glucose Neurology Animals Newborn Positron emission tomography Hypoxia-Ischemia Brain Immature brain medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Experimental neurology. 330 |
| ISSN: | 1090-2430 |
| Popis: | Neonatal hypoxia ischemia (HI) is the main cause of newborn mortality and morbidity. Preclinical studies have shown that the immature rat brain is more resilient to HI injury, suggesting innate mechanisms of neuroprotection. During neonatal period brain metabolism experience changes that might greatly affect the outcome of HI injury. Therefore, the aim of the present study was to investigate how changes in brain metabolism interfere with HI outcome in different stages of CNS development. For this purpose, animals were divided into 6 groups: HIP3, HIP7 and HIP11 (HI performed at postnatal days 3, 7 and 11, respectively), and their respective shams. In vivo [18F]FDG micro positron emission tomography (microPET) imaging was performed 24 and 72 h after HI, as well as ex-vivo assessments of glucose and beta-hydroxybutyrate (BHB) oxidation. At adulthood behavioral tests and histology were performed. Behavioral and histological analysis showed greater impairments in HIP11 animals, while HIP3 rats were not affected. Changes in [18F]FDG metabolism were found only in the lesion area of HIP11, where a substantial hypometabolism was detected. Furthermore, [18F]FDG hypometabolism predicted impaired cognition and worst histological outcomes at adulthood. Finally, substrate oxidation assessments showed that glucose oxidation remained unaltered and higher level of BHB oxidation found in P3 animals, suggesting a more resilient metabolism. Overall, present results show [18F]FDG microPET predicts long-term injury outcome and suggests that higher BHB utilization is one of the mechanisms that confer the intrinsic neuroprotection to the immature brain and should be explored as a therapeutic target for treatment of HI. |
| Databáze: | OpenAIRE |
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