Pathophysiology of hypoxic–ischemic encephalopathy: a review of the past and a view on the future

Greco, Pantaleo; Nencini, Giulia; Piva, Isabella; Scioscia, Marco; Volta, C. A.; Spadaro, Savino; Neri, Margherita; Bonaccorsi, Gloria; Greco, Francesca; Cocco, I; Sorrentino, Felice; D’Antonio, F.; Nappi, Luigi

doi:10.1007/s13760-020-01308-3

Cited by 166 publications

(111 citation statements)

References 75 publications

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“…Accordingly, we found that the activities of SOD and GSH-px were significantly decreased after HIBD in vitro and in vivo and that the total cellular ROS levels increased in vitro ; neferine treatment could significantly suppress this response. Mitochondria perform several important functions, and numerous studies have suggested that mitochondrial dysfunction results in the production of large amounts of ROS after HIBD, which cannot be immediately removed; they accumulate excessively due to metabolic interruption, thereby playing a central role in HIBD-induced neurodegeneration [ 42 ]. Using a MitoSOX fluorescent probe to detect mitochondrial ROS in vitro , we found that red fluorescence was significantly higher in CoCl 2 -stimulated PC12 cells, which was reversed by neferine treatment.…”

Section: Discussionmentioning

confidence: 99%

Neferine Protects against Hypoxic‐Ischemic Brain Damage in Neonatal Rats by Suppressing NLRP3‐Mediated Inflammasome Activation

Zhu

Huang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Hypoxic-ischemic encephalopathy (HIE) is recognized as the main cause of neonatal death, and efficient treatment strategies remain limited. Given the prevalence of HIE and the associated fatality, further studies on its pathogenesis are warranted. Oxidative stress and neuroinflammatory injury are two important factors leading to brain tissue injury and nerve cell loss in HIE. Neferine, an alkaloid extracted from lotus seed embryo, exerts considerable effects against several diseases such as cancers and myocardial injury. In this study, we demonstrated the neuroprotective effect of neferine on HIE and hypothesized that it involves the inhibition of neuronal pyroptosis, thereby ameliorating neurological inflammation and oxidative stress. We demonstrated that the mRNA levels of proteins associated with pyroptosis including caspase-1, the caspase adaptor ASC, gasdermin D, interleukin- (IL-) 18, IL-1β, and some inflammatory factors were significantly increased in neonatal HIBD model rats compared to those in the control group. The increase in these factors was significantly suppressed by treatment with neferine. We stimulated PC12 cells with CoCl2 to induce neuronal HIBD in vitro and investigated the relationship between neferine and pyroptosis by altering the expression of the NLRP3 inflammasome. The overexpression of NLRP3 partially reversed the neuroprotective effect of neferine on HIBD, whereas NLRP3 knockdown further inhibited caspase-1 activation and IL-1β and IL18 expression. In addition, simultaneous alteration of NLRP3 expression induced changes in intracellular oxidative stress levels after HIBD. These findings indicate that neferine ameliorates neuroinflammation and oxidative stress injury by inhibiting pyroptosis after HIBD. Our study provides valuable information for future studies on neferine with respect to neuroinflammation and pyroptosis.

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Section: Discussionmentioning

confidence: 99%

Neferine Protects against Hypoxic‐Ischemic Brain Damage in Neonatal Rats by Suppressing NLRP3‐Mediated Inflammasome Activation

Zhu

Huang

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Also, some novel neuroprotectants have been shown to be of great value in HIE therapy by regulating oxidative stress, inflammatory response, glutaminergic excitotoxicity, and apoptosis [ 37 , 38 ]. After an HI event, there is increased regeneration of pathways, which may be enhanced by novel treatments [ 39 ]. Recently, stem cell-based therapy has been revealed to have the potential to rescue and replace the ischemic tissue caused by HI and may facilitate endogenous brain repair [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Role of Sirtuin-1 in Neonatal Hypoxic-Ischemic Encephalopathy and Its Underlying Mechanism

2020

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Background Neonatal hypoxic-ischemic encephalopathy (HIE) is a dreaded disease and one of the leading causes of severe neurological dysfunction in neonates. The present study explored the functions of Sirtuin-1 (SIRT1) in neonatal HIE. Material/Methods A HIE neonatal rat model was generated to determine SIRT1 levels in brain tissues. Cell apoptosis and cell viability were analyzed by flow cytometry and MTT assay. qRT-PCR and Western blot analysis were used to assess gene mRNA and protein levels. Subsequently, the effect of SIRT1 on HIE was investigated in vitro by constructing an oxygen-glucose deprivation (OGD) cell model. Results The effective construction of the HIE rat model was confirmed by the enhanced brain cell apoptosis and the increased expression of HIE-related molecular markers, including S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE). SIRT1 expression was downregulated in HIE rat brain tissues. These findings indicated that SIRT1 was downregulated in neuronal cells subjected to OGD. In addition, enhanced cell viability and reduced cell apoptosis were observed, suggesting that SIRT1 overexpression relieved OGD-induced neuronal cell injury. Transfection with SIRT1-siRNA further increased OGD-induced neuronal cell injury, evidenced by decreased cell viability and enhanced cell apoptosis. Finally, SIRT1 overexpression significantly downregulated p-p65 protein expression. Conclusions Our findings revealed that SIRT1 may be a novel and promising therapy target for HIE treatment.

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“…Greco et al 6 . reported an incidence of hypoxic‐ischemic encephalopathy of about 1.5 cases per 1000 live births, which is much higher than the 0.96 per 1000 live births reported by Beta et al 1 …”

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confidence: 83%

Re: Maternal and neonatal complications of fetal macrosomia: cohort study

Rehm

Thahir

2020

Ultrasound in Obstet & Gyne

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Pathophysiology of hypoxic–ischemic encephalopathy: a review of the past and a view on the future

Cited by 166 publications

References 75 publications

Neferine Protects against Hypoxic‐Ischemic Brain Damage in Neonatal Rats by Suppressing NLRP3‐Mediated Inflammasome Activation

Neferine Protects against Hypoxic‐Ischemic Brain Damage in Neonatal Rats by Suppressing NLRP3‐Mediated Inflammasome Activation

Role of Sirtuin-1 in Neonatal Hypoxic-Ischemic Encephalopathy and Its Underlying Mechanism

Re: Maternal and neonatal complications of fetal macrosomia: cohort study

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