scholarly journals Scutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathway

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Rui-Ze Niu ◽  
Liu-Lin Xiong ◽  
Hao-Li Zhou ◽  
Lu-Lu Xue ◽  
Qing-Jie Xia ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Ischemic Injury ◽  
Hypoxic Ischemic Encephalopathy ◽  
Qrt Pcr ◽  
Pharmacological Analysis ◽  
Ischemic Encephalopathy ◽  
Hypoxic Ischemic Injury

Abstract Background Neonatal hypoxic-ischemic encephalopathy (HIE) refers to the perinatal asphyxia caused by the cerebral hypoxic-ischemic injury. The current study was aimed at investigating the therapeutic efficacy of Scutellarin (Scu) administration on neurological impairments induced by hypoxic-ischemic injury and exploring the underlying mechanisms. Methods Primary cortical neurons were cultured and subjected to oxygen–glucose deprivation (OGD), and then treated with Scu administration. The growth status of neurons was observed by immunofluorescence staining of TUJ1 and TUNEL. Besides, the mRNA level of growth-associated protein 43 (GAP43) in OGD neurons with Scu treatment was detected by quantitative real-time polymerase chain reaction (qRT-PCR). To further verify the role of GAP43 in Scu treatment, GAP43 siRNA and knockout were applied in vitro and in vivo. Moreover, behavioral evaluations were performed to elucidate the function of GAP43 in the Scu-ameliorated long-term neurological impairments caused by HI insult. The underlying biological mechanism of Scu treatment was further elucidated via network pharmacological analysis. Finally, the interactive genes with GAP43 were identified by Gene MANIA and further validated by qRT-PCR. Results Our data demonstrated that Scu treatment increased the number of neurons and axon growth, and suppressed cell apoptosis in vitro. And the expression of GAP43 was downregulated after OGD, but reversed by Scu administration. Besides, GAP43 silencing aggravated the Scu-ameliorated neuronal death and axonal damage. Meanwhile, GAP43 knockout enlarged brain infarct area and deteriorated the cognitive and motor dysfunctions of HI rats. Further, network pharmacological analysis revealed the drug targets of Scu participated in such biological processes as neuronal death and regulation of neuronal death, and apoptosis-related pathways. GAP43 exhibited close relationship with PTN, JAK2 and STAT3, and GAP43 silencing upregulated the levels of PTN, JAK2 and STAT3. Conclusions Collectively, our findings revealed Scu treatment attenuated long-term neurological impairments after HI by suppressing neuronal death and enhancing neurite elongation through GAP43-dependent pathway. The crucial role of Scutellarin in neuroprotection provided a novel possible therapeutic agent for the treatment of neonatal HIE. Graphic abstract

scholarly journals Prognostic role of acute kidney injury on long-term outcome in infants with hypoxic-ischemic encephalopathy

2019 ◽  
Vol 35 (3) ◽  
pp. 477-483 ◽  
Author(s):  
Francesco Cavallin ◽  
Giulia Rubin ◽  
Enrico Vidal ◽  
Elisa Cainelli ◽  
Luca Bonadies ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Hypoxic Ischemic Encephalopathy ◽  
Prognostic Role ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Ischemic Encephalopathy

scholarly journals To evaluate the role of MRI in infants with suspected hypoxic ischemic encephalopathy and prognosticating neurological outcome at end of one year

2017 ◽  
Vol 5 (5) ◽  
pp. 1893
Author(s):  
Shreyas Ramachandran ◽  
Smiti Sripathi
Keyword(s):  
Clinical Outcome ◽  
Motor Development ◽  
Perinatal Asphyxia ◽  
Hypoxic Ischemic Encephalopathy ◽  
Neurological Outcomes ◽  
Common Causes ◽  
One Year ◽  
Ischemic Encephalopathy

Background: Hypoxic ischemic encephalopathy (HIE) is one the common causes of neonatal fatality due to perinatal asphyxia. The long-term outcomes of HIE are impaired mental and motor development, hearing loss, recurrent seizures and cerebral palsy. MRI is increasingly becoming the gold standard in diagnosis of HIE as it involves no radiation and can be performed during a neonates physiological sleep. To evaluate the role of MRI in infants with suspected hypoxic ischemic encephalopathy in prognosticating neurological outcomes at end of one year.Methods: A total of 50 patients were included in the study who underwent MRI of brain. A clinical follow up was done at the end of one year.Results: The sensitivity of MRI in prognosticating clinical outcome was 72% and specificity was 71% while PPV and NPV was 86% and 50% respectively.Conclusions: MRI is a useful modality to assess early changes in HIE and it can prognosticate clinical outcome.

Neuroprotective Agents for Neonates with Hypoxic-Ischemic Encephalopathy

2021 ◽  
Vol 40 (6) ◽  
pp. 406-413
Author(s):  
Keliana O'Mara ◽  
Christopher McPherson
Keyword(s):  
Therapeutic Hypothermia ◽  
Ischemic Injury ◽  
Hypoxic Ischemic Encephalopathy ◽  
Neuroprotective Agents ◽  
Neuroprotective Effects ◽  
Animal Data ◽  
Neurodevelopmental Impairment ◽  
Pharmacologic Agents ◽  
Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) remains a significant source of long-term neurodevelopmental impairment despite overall improvements in survival without disability in neonates who undergo therapeutic hypothermia. Each phase in the evolution of hypoxic-ischemic injury presents potential pharmacologic targets for neuroprotective agents. Melatonin is a promising emerging therapy for early phases of ischemic injury, but utility is currently limited by the lack of pharmaceutical-grade products. Magnesium has been extensively studied for its neuroprotective effects in the preterm population. Studies in neonates with HIE have produced mixed outcomes. Erythropoietin use in HIE with or without therapeutic hypothermia appears to be safe and may provide additional benefit. Dexmedetomidine, N-acetylcysteine, xenon, and topiramate all have promising animal data, but need additional human trials to elucidate what role they may play in HIE. Frequent review of existing literature is required to ensure provision of evidence-based pharmacologic agents for neuroprotection following HIE.

THE ROLE OF POLYETHYLENIMINE IN ENHANCING PERFORMANCE OF GLUTAMATE BIOSENSORS

2018 ◽  
Vol 8 (3) ◽  
pp. 36-41
Author(s):  
Diep Do Thi Hong ◽  
Duong Le Phuoc ◽  
Hoai Nguyen Thi ◽  
Serra Pier Andrea ◽  
Rocchitta Gaia
Keyword(s):  
First Generation ◽  
Good Reproducibility ◽  
Complex Matrices ◽  
Long Term Stability ◽  
In Vitro Characterization ◽  
Glutamate Oxidase

Background: The first biosensor was constructed more than fifty years ago. It was composed of the biorecognition element and transducer. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples Glutamate is important biochemicals involved in energetic metabolism and neurotransmission. Therefore, biosensors requires the development a new approach exhibiting high sensibility, good reproducibility and longterm stability. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples. The aims of this work: To find out which concentration of polyethylenimine (PEI) exhibiting the most high sensibility, good reproducibility and long-term stability. Methods: We designed and developed glutamate biosensor using different concentration of PEI ranging from 0% to 5% at Day 1 and Day 8. Results: After Glutamate biosensors in-vitro characterization, several PEI concentrations, ranging from 0.5% to 1% seem to be the best in terms of VMAX, the KM; while PEI content ranging from 0.5% to 1% resulted stable, PEI 1% displayed an excellent stability. Conclusions: In the result, PEI 1% perfomed high sensibility, good stability and blocking interference. Furthermore, we expect to develop and characterize an implantable biosensor capable of detecting glutamate, glucose in vivo. Key words: Glutamate biosensors, PEi (Polyethylenimine) enhances glutamate oxidase, glutamate oxidase biosensors

scholarly journals The Kynurenic Acid Analog SZR72 Enhances Neuronal Activity after Asphyxia but Is Not Neuroprotective in a Translational Model of Neonatal Hypoxic Ischemic Encephalopathy

2021 ◽  
Vol 22 (9) ◽  
pp. 4822
Author(s):  
Viktória Kovács ◽  
Gábor Remzső ◽  
Tímea Körmöczi ◽  
Róbert Berkecz ◽  
Valéria Tóth-Szűki ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Kynurenic Acid ◽  
Neuronal Damage ◽  
Brain Regions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Hippocampal Field ◽  
Power Spectral ◽  
Density Values ◽  
Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates. Hypothermia offers partial neuroprotection warranting research for additional therapies. Kynurenic acid (KYNA), an endogenous product of tryptophan metabolism, was previously shown to be beneficial in rat HIE models. We sought to determine if the KYNA analog SZR72 would afford neuroprotection in piglets. After severe asphyxia (pHa = 6.83 ± 0.02, ΔBE = −17.6 ± 1.2 mmol/L, mean ± SEM), anesthetized piglets were assigned to vehicle-treated (VEH), SZR72-treated (SZR72), or hypothermia-treated (HT) groups (n = 6, 6, 6; Tcore = 38.5, 38.5, 33.5 °C, respectively). Compared to VEH, serum KYNA levels were elevated, recovery of EEG was faster, and EEG power spectral density values were higher at 24 h in the SZR72 group. However, instantaneous entropy indicating EEG signal complexity, depression of the visual evoked potential (VEP), and the significant neuronal damage observed in the neocortex, the putamen, and the CA1 hippocampal field were similar in these groups. In the caudate nucleus and the CA3 hippocampal field, neuronal damage was even more severe in the SZR72 group. The HT group showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions. In summary, SZR72 appears to enhance neuronal activity after asphyxia but does not ameliorate early neuronal damage in this HIE model.

Correlation between magnesium and potassium contents in muscle: role of Na(+)-K+ pump

1993 ◽  
Vol 264 (2) ◽  
pp. C457-C463 ◽  
Author(s):  
I. Dorup ◽  
T. Clausen
Keyword(s):  
Extensor Digitorum Longus ◽  
Extensor Digitorum ◽  
Deficient Diet ◽  
Young Rats ◽  
Wide Range ◽  
86Rb Influx

In young rats fed a Mg(2+)-deficient diet for 3 wk, Mg2+ and K+ contents in soleus and extensor digitorum longus muscles were significantly reduced and closely correlated. In isolated soleus muscles, Mg2+ depletion induced an even more pronounced loss of K+, and Mg2+ and K+ contents were correlated over a wide range (r = 0.95, P < 0.001). Extracellular Mg2+ (0-1.2 mM) caused no change in total or ouabain-suppressible 86Rb influx. After long-term incubation in Ca(2+)-Mg(2+)-free buffer with EDTA and EGTA, cellular Mg2+ and K+ contents were reduced by 35 and 15%, respectively, without any reduction in ATP and total or ouabain-suppressible 86Rb influx. In Mg(2+)-depleted muscles 42K efflux was increased by up to 42%, and repletion with Mg2+ produced a graded decrease. We conclude that Mg2+ and K+ contents are closely correlated in muscles Mg2+ depleted in vivo or in vitro and that neither extracellular nor moderate intracellular Mg2+ depletion affects total or Na(+)-K+ pump-mediated K+ influx. The reduced K+ content may rather be related to increased K+ efflux from the muscles.

scholarly journals Protective Effects ofN-Acetyl-L-Cysteine in Human Oligodendrocyte Progenitor Cells and Restoration of Motor Function in Neonatal Rats with Hypoxic-Ischemic Encephalopathy

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Dongsun Park ◽  
Kyungha Shin ◽  
Ehn-Kyoung Choi ◽  
Youngjin Choi ◽  
Ja-Young Jang ◽  
...  
Keyword(s):  
White Matter ◽  
Progenitor Cells ◽  
Hypoxic Ischemic Encephalopathy ◽  
Oligodendrocyte Progenitor Cells ◽  
Protective Effects ◽  
Neonatal Rats ◽  
Motor Functions ◽  
Ischemic Encephalopathy

Objective. Since oligodendrocyte progenitor cells (OPCs) are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE), the present study was aimed at investigating the protective effects ofN-acetyl-L-cysteine (NAC), a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats.Methods. Inin vitrostudy, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. Inin vivostudy, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed.Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE.Conclusion. The results indicate that NAC exerts neuroprotective effectsin vitroandin vivoby preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.

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