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Differential glucose and beta-hydroxybutyrate metabolism confers an intrinsic neuroprotection to the immature brain in a rat model of neonatal hypoxia ischemia.

Abstract：

: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.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Odorcyk FK,Duran-Carabali LE,Rocha DS,Sanches EF,Martini AP,Venturin GT,Greggio S,da Costa JC,Kucharski LC,Zimmer ER,Netto CA

doi

10.1016/j.expneurol.2020.113317

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

113317

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(20)30148-5

journal_volume

330

pub_type

杂志文章

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