Apoptosis-related proteins are potential markers of neonatal hypoxic–ischemic encephalopathy (HIE) injury

Hernández-Jiménez, Macarena; Sacristán, Silvia; Morales, Carmen; García-Villanueva, Mercedes; García-Fernández, Eugenia; Alcázar, Alberto; González, Víctor; Martín, M. Elena

doi:10.1016/j.neulet.2013.11.019

Cited by 13 publications

(11 citation statements)

References 31 publications

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“…A previous study demonstrated that the brain homogenates from preconditioned mice were able to strengthen the tolerance to hypoxia and protect the animals from hypoxic injury (Lu et al, 2005). Recent studies have examined the potential biomarkers of HPC (Hernandez-Jimenez et al, 2014; Lv et al, 2015). Cui et al (2015) performed a proteomic study to profile the patterns of protein expression in HPC mouse brains.…”

Section: Introductionmentioning

confidence: 99%

UHPLC-QTOFMS-Based Metabolomic Analysis of the Hippocampus in Hypoxia Preconditioned Mouse

et al. 2019

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Background: Hypoxia appears in a number of extreme environments, including high altitudes, the deep sea, and during aviation, and occurs in cancer, cardiovascular disease, respiratory failures and neurological disorders. Though it is well recognized that hypoxic preconditioning (HPC) exerts endogenous neuroprotective effect against severe hypoxia, the mediators and underlying molecular mechanism for the protective effect are still not fully understood. This study established a hippocampus metabolomics approach to explore the alterations associated with HPC.Methods: In this study, an animal model of HPC was established by exposing the adult BALB/c mice to acute repetitive hypoxia four times. Ultra-high liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) in combination with univariate and multivariate statistical analyses was employed to deciphering metabolic changes associated with HPC in hippocampus tissue. MetaboAnalyst 3.0 was used to construct HPC related metabolic pathways.Results: The significant metabolic differences in hippocampus between the HPC groups and control were observed, indicating that HPC mouse model was successfully established and HPC could caused significant metabolic changes. Several key metabolic pathways were found to be acutely perturbed, including phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, phenylalanine metabolism, glutathione metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, citrate cycle, and glycerophospholipid metabolism.Conclusion: The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the neuroprotective mechanism of HPC.

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Section: Introductionmentioning

confidence: 99%

UHPLC-QTOFMS-Based Metabolomic Analysis of the Hippocampus in Hypoxia Preconditioned Mouse

et al. 2019

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“…The complex pathophysiology of HI brain injury provides multiple targets associated with different time points of the disease process. For instance, in the early stages of the disease, therapies are mainly focused on reducing the oxidative, excitotoxic and apoptotic mediators [ 30 , 31 ], whereas in the later phase of the disease, stimulation of the neurotrophic properties and reductions in the levels of inflammatory cytokines can promote neuronal and oligodendrocyte regeneration [ 22 , 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of endoplasmic reticulum stress is involved in the neuroprotective effect of aFGF in neonatal hypoxic-ischaemic brain injury

Wang

Pan

et al. 2017

Oncotarget

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Acidic fibroblast growth factor (aFGF) has been shown to exert neuroprotective effects in experimental models and human patients. In this study, we investigated whether aFGF intranasal-treatment protected against neonatal hypoxic-ischaemic brain injury and evaluated the role of endoplasmic reticulum stress. The Rice-Vannucci model of neonatal hypoxic-ischaemic brain injury was used in 7-day-old rats, which were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia. Intranasal aFGF or vehicle was administered immediately after hypoxic-ischaemic injury (100 ng/g) and then twice a day for 1 week to evaluate the long-term effects. Here we reported that intranasal-treatment with aFGF significantly reduced hypoxic-ischaemic brain infarct volumes and the protective effects were at least partially via inhibiting endoplasmic reticulum stress. In addition, aFGF exerted long-term neuroprotective effects against brain atrophy and neuron loss at 7-day after injury. Our data indicate that therapeutic strategies targeting endoplasmic reticulum stress may be promising to the treatment of neonatal hypoxic-ischaemic brain injury.

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“…Both the intrinsic and extrinsic cell death pathways (i.e., mitochondrial membrane-mediated and death receptor-mediated apoptosis) have been implicated in intrapartum asphyxia and neonatal HI brain injury [39]. At 24 h after insult, induction of apoptotic/necrotic cell death pathways was evident in the spiny mouse model of intrapartum asphyxia, with increased HSP70 mRNA expression in the cortex, p53 mRNA expression in the DGM, and marked increases in TUNEL-positive cells within all of the 4 brain regions analyzed with the most pronounced changes in the corpus callosum and hippocampus.…”

Section: K3a-apc To Prevent Neuronal Apoptotic Cell Death Following mentioning

confidence: 99%

Evaluation of 3K3A-Activated Protein C to Treat Neonatal Hypoxic Ischemic Brain Injury in the Spiny Mouse

et al. 2019

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Neonatal hypoxic ischemic encephalopathy (HIE) resulting from intrapartum asphyxia is a global problem that causes severe disabilities and up to 1 million deaths annually. A variant form of activated protein C, 3K3A-APC, has cytoprotective properties that attenuate brain injury in models of adult stroke. In this study, we compared the ability of 3K3A-APC and APC (wild-type (wt)) to attenuate neonatal brain injury, using the spiny mouse (Acomys cahirinus) model of intrapartum asphyxia. Pups were delivered at 38 days of gestation (term = 39 days), with an intrapartum hypoxic insult of 7.5 min (intrapartum asphyxia cohort), or immediate removal from the uterus (control cohort). After 1 h, pups received a subcutaneous injection of 3K3A-APC or wild-type APC (wtAPC) at 7 mg/kg, or vehicle (saline). At 24 h of age, pups were killed and brain tissue was collected for measurement of inflammation and cell death using RT-qPCR and histopathology. Intrapartum asphyxia increased weight loss, inflammation, and apoptosis/necrosis in the newborn brain. 3K3A-APC administration maintained body weight and ameliorated an asphyxia-induced increase of TGFβ1 messenger RNA expression in the cerebral cortex, immune cell aggregation in the corpus callosum, and cell death in the deep gray matter and hippocampus. In the cortex, 3K3A-APC appeared to exacerbate the immune response to the hypoxic ischemic insult. While wtAPC reduced cell death in the corpus callosum and hippocampus following intrapartum asphyxia, it increased markers of neuro-inflammation and cell death in control pups. These findings suggest 3K3A-APC administration may be a useful therapy to reduce cell death and neonatal brain injury associated with HIE.

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Apoptosis-related proteins are potential markers of neonatal hypoxic–ischemic encephalopathy (HIE) injury

Cited by 13 publications

References 31 publications

UHPLC-QTOFMS-Based Metabolomic Analysis of the Hippocampus in Hypoxia Preconditioned Mouse

UHPLC-QTOFMS-Based Metabolomic Analysis of the Hippocampus in Hypoxia Preconditioned Mouse

Inhibition of endoplasmic reticulum stress is involved in the neuroprotective effect of aFGF in neonatal hypoxic-ischaemic brain injury

Evaluation of 3K3A-Activated Protein C to Treat Neonatal Hypoxic Ischemic Brain Injury in the Spiny Mouse

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