Long-term changes in metabolic brain network drive memory impairments in rats following neonatal hypoxia-ischemia

Azevedo, Pâmella Nunes; Zanirati, Gabriele; Venturin, Gianina Teribele; Schu, Guilherme; Durán‐Carabali, Luz Elena; Odorcyk, Felipe Kawa; Soares, Andrey Vinicius; Laguna, Gabriela de Oliveira; Netto, Carlos Alexandre; Zimmer, Eduardo R.; Costa, Jaderson Costa da; Greggio, Samuel

doi:10.1016/j.nlm.2020.107207

Cited by 14 publications

(14 citation statements)

References 44 publications

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“…A recent study using the HI model at PND7 demonstrated changes in the architecture of MBN even in the absence of significant glucose hypometabolism (Nunes Azevedo et al 2020), which is in concordance with outcomes observed in animals exposed to EC. In spite that early EC did not protect against the uncoupling between brain regions induced by HI, the MBN remodeling after neonatal insult could be critical to mediate recovery mechanisms.…”

Section: Discussionsupporting

confidence: 79%

“…Further analyses were conducted by MINC tools (http://www.bic.mni.mcgill.ca/ServicesSoftware) (Nunes Azevedo et al. 2020).…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, SUVs of all brain regions were normalized by the pons and expressed as relative standardized uptake value (SUVr). Further analyses were conducted by MINC tools (www.bic.mni.mcgill.ca/Servi cesSo ftware) (Nunes Azevedo et al 2020).…”

Section: Micro-positron Emission Tomography Imaging and Analysismentioning

confidence: 99%

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Pre‐ and early postnatal enriched environmental experiences prevent neonatal hypoxia‐ischemia late neurodegeneration via metabolic and neuroplastic mechanisms

Durán‐Carabali

Odorcyk

Greggio

et al. 2020

Journal of Neurochemistry

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Prenatal and early postnatal periods are important for brain development and neural function. Neonatal insults such as hypoxia‐ischemia (HI) causes prolonged neural and metabolic dysregulation, affecting central nervous system maturation. There is evidence that brain hypometabolism could increase the risk of adult‐onset neurodegenerative diseases. However, the impact of non‐pharmacologic strategies to attenuate HI‐induced brain glucose dysfunction is still underexplored. This study investigated the long‐term effects of early environmental enrichment in metabolic, cell, and functional responses after neonatal HI. Thereby, male Wistar rats were divided according to surgical procedure, sham, and HI (performed at postnatal day 3), and the allocation to standard (SC) or enriched condition (EC) during gestation and lactation periods. In‐vivo cerebral metabolism was assessed by means of [18F]‐FDG micro‐positron emission tomography, and cognitive, biochemical, and histological analyses were performed in adulthood. Our findings reveal that HI causes a reduction in glucose metabolism and glucose transporter levels as well as hyposynchronicity in metabolic brain networks. However, EC during prenatal or early postnatal period attenuated these metabolic disturbances. A positive correlation was observed between [18F]‐FDG values and volume ratios in adulthood, indicating that preserved tissue by EC is metabolically active. EC promotes better cognitive scores, as well as down‐regulation of amyloid precursor protein in the parietal cortex and hippocampus of HI animals. Furthermore, growth‐associated protein 43 was up‐regulated in the cortex of EC animals. Altogether, results presented support that EC during gestation and lactation period can reduce HI‐induced impairments that may contribute to functional decline and progressive late neurodegeneration.

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Section: Discussionsupporting

confidence: 79%

“…Further analyses were conducted by MINC tools (http://www.bic.mni.mcgill.ca/ServicesSoftware) (Nunes Azevedo et al. 2020).…”

Section: Methodsmentioning

confidence: 99%

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Pre‐ and early postnatal enriched environmental experiences prevent neonatal hypoxia‐ischemia late neurodegeneration via metabolic and neuroplastic mechanisms

Durán‐Carabali

Odorcyk

Greggio

et al. 2020

Journal of Neurochemistry

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“…Under pathological conditions, areas may exhibit severe hypoxia (partial oxygen pressure of < 0.1 kPa) or anoxia ( Liu et al, 1995 ; Erecińska and Silver, 2001 ). Neurons in the CNS are particularly sensitive to hypoxia, and hypoxia-induced changes of oxygen metabolism and mitochondrial functions can result in destructive structural and functional changes in neurons, leading to their death ( Azevedo et al, 2020 ; Kumari et al, 2020 ). Ischemic stroke is a widespread disease, and is the main source of hypoxic brain stress ( Ratan et al, 2007 ; Virani et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Inducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease

Митрошина

Savyuk

Ponimaskin

et al. 2021

Front. Cell Dev. Biol.

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Hypoxia is one of the most common pathological conditions, which can be induced by multiple events, including ischemic injury, trauma, inflammation, tumors, etc. The body’s adaptation to hypoxia is a highly important phenomenon in both health and disease. Most cellular responses to hypoxia are associated with a family of transcription factors called hypoxia-inducible factors (HIFs), which induce the expression of a wide range of genes that help cells adapt to a hypoxic environment. Basic mechanisms of adaptation to hypoxia, and particularly HIF functions, have being extensively studied over recent decades, leading to the 2019 Nobel Prize in Physiology or Medicine. Based on their pivotal physiological importance, HIFs are attracting increasing attention as a new potential target for treating a large number of hypoxia-associated diseases. Most of the experimental work related to HIFs has focused on roles in the liver and kidney. However, increasing evidence clearly demonstrates that HIF-based responses represent an universal adaptation mechanism in all tissue types, including the central nervous system (CNS). In the CNS, HIFs are critically involved in the regulation of neurogenesis, nerve cell differentiation, and neuronal apoptosis. In this mini-review, we provide an overview of the complex role of HIF-1 in the adaptation of neurons and glia cells to hypoxia, with a focus on its potential involvement into various neuronal pathologies and on its possible role as a novel therapeutic target.

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“…Compared with adults, the developing brain is high in plasticity and also more susceptible to external stimuli (Rocha-Ferreira and Hristova, 2016). For example, it is shown that HIP3 (suffered to HI injury at postnatal day 3) rat tolerates better than HIP11 (suffered to HI injury at postnatal day 11) rat because of its more resilient metabolism (Odorcyk et al, 2020), but the sustained changes of brain metabolism may in turn influence the long-term cognitive development (Azevedo et al, 2020). Furthermore, although the immature brain can exhibit a certain resistance when it is subjected to hypoxia alone (Johnston et al, 2001), the coexistence of hypoxia and ischemia could reduce the resistance of neonatal brain, exaggerate neuronal excitability, and thereby cause neurons to more likely be damaged, and the injury would develop for several days (Johnston et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The Function of the NMDA Receptor in Hypoxic-Ischemic Encephalopathy

2020

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Hypoxic-ischemic encephalopathy (HIE) is one of the main forms of neonatal brain injury which could lead to neonatal disability or even cause neonatal death. Therefore, HIE strongly affects the health of newborns and brings heavy burden to the family and society. It has been well studied that N-methyl-D-aspartate (NMDA) receptors are involved in the excitotoxicity induced by hypoxia ischemia in adult brain. Recently, it has been shown that the NMDA receptor also plays important roles in HIE. In the present review, we made a summary of the molecular mechanism of NMDA receptor in the pathological process of HIE, focusing on the distinct role of GluN2A-and GluN2Bcontaining NMDA receptor subtypes and aiming to provide some insights into the clinical treatment and drug development of HIE.

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Long-term changes in metabolic brain network drive memory impairments in rats following neonatal hypoxia-ischemia

Cited by 14 publications

References 44 publications

Pre‐ and early postnatal enriched environmental experiences prevent neonatal hypoxia‐ischemia late neurodegeneration via metabolic and neuroplastic mechanisms

Pre‐ and early postnatal enriched environmental experiences prevent neonatal hypoxia‐ischemia late neurodegeneration via metabolic and neuroplastic mechanisms

Hypoxia-Inducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease

The Function of the NMDA Receptor in Hypoxic-Ischemic Encephalopathy

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