Hypoxic-Ischemic Brain Injury after Perinatal Asphyxia as a Possible Factor in the Pathology of Alzheimer’s Disease

Tarkowska, A

doi:10.36255/exonpublications.cerebralischemia.2021.perinatalasphyxia

Cited by 7 publications

(10 citation statements)

References 96 publications

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“…Hypoxia can be not only an isolated pathology but also be associated with a variety of CNS diseases, such as Alzheimer’s disease, Parkinson’s disease, etc. [ 46 , 47 ]. Therefore, approaches that increase the brain’s resistance to hypoxia are of great practical value.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Brain- and Glial Cell Line-Derived Neurotrophic Factors Is Neuroprotective in an Animal Model of Acute Hypobaric Hypoxia

Gavrish

Urazov

Mishchenko

et al. 2022

IJMS

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Currently, the role of the neurotrophic factors BDNF and GDNF in maintaining the brain’s resistance to the damaging effects of hypoxia and functional recovery of neural networks after exposure to damaging factors are actively studied. The assessment of the effect of an increase in the level of these neurotrophic factors in brain tissues using genetic engineering methods on the resistance of laboratory animals to hypoxia may pave the way for the future clinical use of neurotrophic factors BDNF and GDNF in the treatment of hypoxic damage. This study aimed to evaluate the antihypoxic and neuroprotective properties of BDNF and GDNF expression level increase using adeno-associated viral vectors in modeling hypoxia in vivo. To achieve overexpression of neurotrophic factors in the central nervous system’s cells, viral constructs were injected into the brain ventricles of newborn male C57Bl6 (P0) mice. Acute hypobaric hypoxia was modeled on the 30th day after the injection of viral vectors. Survival, cognitive, and mnestic functions in the late post-hypoxic period were tested. Evaluation of growth and weight characteristics and the neurological status of animals showed that the overexpression of neurotrophic factors does not affect the development of mice. It was found that the use of adeno-associated viral vectors increased the survival rate of male mice under hypoxic conditions. The present study indicates that the neurotrophic factors’ overexpression, induced by the specially developed viral constructs carrying the BDNF and GDNF genes, is a prospective neuroprotection method, increasing the survival rate of animals after hypoxic injury.

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Section: Discussionmentioning

confidence: 99%

Overexpression of Brain- and Glial Cell Line-Derived Neurotrophic Factors Is Neuroprotective in an Animal Model of Acute Hypobaric Hypoxia

Gavrish

Urazov

Mishchenko

et al. 2022

IJMS

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“…Perinatal asphyxia in mice causes delayed damage to the hippocampus and associated learning and spatial memory deficits [ 42 , 43 , 44 ]. Significantly higher levels of amyloid protein precursor and total tau protein, increased tau protein phosphorylation, decreased hypoxia-inducible factor alpha [ 45 , 46 ], lower levels of amyloid degrading neprilysin, increased amyloid accumulation with activation of astrocytes and microglia have been shown in the brain after perinatal asphyxia [ 42 , 47 ]. Total tau protein levels in hypothermic-treated ischemic brain injury, as measured by experimental microdialysis [ 47 ], correlated well with neonatal tau protein levels in blood in hypoxic-ischemic encephalopathy treated with hypothermia [ 13 ].…”

Section: Brain Neuropathology After Perinatal Asphyxiamentioning

confidence: 99%

“…There is increasing evidence that the neuropathology induced in the neonate’s brain during and after perinatal asphyxia is similar to that of adult neurodegenerative diseases, such as Alzheimer’s disease [ 13 , 42 , 44 , 45 , 46 , 49 ]. Additionally, one study found elevated plasma levels of tau protein following asphyxia on days 3 and 7 after birth [ 48 ].…”

Section: Brain Neuropathology After Perinatal Asphyxiamentioning

confidence: 99%

Melatonin: A Potential Candidate for the Treatment of Experimental and Clinical Perinatal Asphyxia

et al. 2023

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Perinatal asphyxia is considered to be one of the major causes of brain neurodegeneration in full-term newborns. The worst consequence of perinatal asphyxia is neurodegenerative brain damage, also known as hypoxic-ischemic encephalopathy. Hypoxic-ischemic encephalopathy is the leading cause of mortality in term newborns. To date, due to the complex mechanisms of brain damage, no effective or causal treatment has been developed that would ensure complete neuroprotection. Although hypothermia is the standard of care for hypoxic-ischemic encephalopathy, it does not affect all changes associated with encephalopathy. Therefore, there is a need to develop effective treatment strategies, namely research into new agents and therapies. In recent years, it has been pointed out that natural compounds with neuroprotective properties, such as melatonin, can be used in the treatment of hypoxic-ischemic encephalopathy. This natural substance with anti-inflammatory, antioxidant, anti-apoptotic and neurofunctional properties has been shown to have pleiotropic prophylactic or therapeutic effects, mainly against experimental brain neurodegeneration in hypoxic-ischemic neonates. Melatonin is a natural neuroprotective hormone, which makes it promising for the treatment of neurodegeneration after asphyxia. It is supposed that melatonin alone or in combination with hypothermia may improve neurological outcomes in infants with hypoxic-ischemic encephalopathy. Melatonin has been shown to be effective in the last 20 years of research, mainly in animals with perinatal asphyxia but, so far, no clinical trials have been performed on a sufficient number of newborns. In this review, we summarize the advantages and limitations of melatonin research in the treatment of experimental and clinical perinatal asphyxia.

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“…There is increasing evidence that the pathology induced in the brains of newborns during and after perinatal asphyxia is similar to that found in adult neurodegenerative diseases such as Alzheimer’s disease [ 3 , 13 , 14 , 15 ]. Experimental studies have shown that perinatal asphyxia in mice causes delayed neuronal death in the hippocampus and significant deficits in memory and spatial learning [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Experimental studies have shown that perinatal asphyxia in mice causes delayed neuronal death in the hippocampus and significant deficits in memory and spatial learning [ 13 , 14 ]. In addition, significantly higher levels of tau protein and its increased phosphorylation, higher concentrations of amyloid protein precursor, decreased hypoxia-inducible factor 1 alpha, lower levels of amyloid-degrading neprilysin, an increased accumulation of amyloid with the activation of microglia, and astrocytes in the brain after asphyxia were found [ 3 , 13 , 15 , 16 ]. Furthermore, one study found elevated blood levels of tau protein after asphyxia on postnatal days 3 and 7 [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Hypothermia after Perinatal Asphyxia Does Not Affect Genes Responsible for Amyloid Production in Neonatal Peripheral Lymphocytes

Tarkowska

Furmaga-Jabłońska

Bogucki

et al. 2022

JCM

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In this study, the expression of the genes of the amyloid protein precursor, β-secretase, presenilin 1 and 2 by RT-PCR in the lymphocytes of newborns after perinatal asphyxia and perinatal asphyxia treated with hypothermia was analyzed at the age of 15–21 days. The relative quantification of Alzheimer’s-disease-related genes was first performed by comparing the peripheral lymphocytes of non-asphyxia control versus those with asphyxia or asphyxia with hypothermia. In the newborns who had perinatal asphyxia, the peripheral lymphocytes presented a decreased expression of the amyloid protein precursor and β-secretase genes. On the other hand, the expression of the presenilin 1 and 2 genes increased in the studied group. The expression of the studied genes in the asphyxia group treated with hypothermia had an identical pattern of changes that were not statistically significant to the asphyxia group. This suggests that the expression of the genes involved in the metabolism of the amyloid protein precursor in the peripheral lymphocytes may be a biomarker of progressive pathological processes in the brain after asphyxia that are not affected by hypothermia. These are the first data in the world showing the role of hypothermia in the gene changes associated with Alzheimer’s disease in the peripheral lymphocytes of newborns after asphyxia.

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Hypoxic-Ischemic Brain Injury after Perinatal Asphyxia as a Possible Factor in the Pathology of Alzheimer’s Disease

Cited by 7 publications

References 96 publications

Overexpression of Brain- and Glial Cell Line-Derived Neurotrophic Factors Is Neuroprotective in an Animal Model of Acute Hypobaric Hypoxia

Overexpression of Brain- and Glial Cell Line-Derived Neurotrophic Factors Is Neuroprotective in an Animal Model of Acute Hypobaric Hypoxia

Melatonin: A Potential Candidate for the Treatment of Experimental and Clinical Perinatal Asphyxia

Hypothermia after Perinatal Asphyxia Does Not Affect Genes Responsible for Amyloid Production in Neonatal Peripheral Lymphocytes

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