Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ische...Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.展开更多
The efficacy and safety of ganglioside in the treatment of neonates who suffer from hypoxic-ischemic encephalopathy(HIE)needs to be fully evaluated.We searched the following databases:PubMed,ScienceDirect,LISTA,CNKI,C...The efficacy and safety of ganglioside in the treatment of neonates who suffer from hypoxic-ischemic encephalopathy(HIE)needs to be fully evaluated.We searched the following databases:PubMed,ScienceDirect,LISTA,CNKI,Chinese biomedical literature database and Wanfang digital journals of full-text database to determine the inclusion and exclusion criteria of papers and a total of 12 papers were included after quality evaluation.Then we conducted the meta-analysis with RevMan5.0 software.The results showed that compared with the control group,the abnormal rate declined in the ganglioside-treated group(relative risk(RR)=0.27,95%confidence interval(CI)=0.05-1.96).NBNA records of the 7,10-14d neonates were improved effectively:RR(95%CI)were 2.28(0.86-3.42)and 2.53(1.04-2.92)respectively.Neural system sequelae incidence was reduced significantly:RR(95%CI)=0.35:(0.15-0.79).Ganglioside treatment could effectively reduce the abnormality rate of head size,improve the neurological score,reduce the incidence of neurological sequelae,and significantly prompt clinical recovery for neonates with HIE.展开更多
BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is one of the leading causes of death and long-term neurological impairment in the pediatric population.Despite a limited number of treatments to cure HIE,stem cell thera...BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is one of the leading causes of death and long-term neurological impairment in the pediatric population.Despite a limited number of treatments to cure HIE,stem cell therapies appear to be a potential treatment option for brain injury resulting from HIE.AIM To investigate the efficacy and safety of stem cell-based therapies in pediatric patients with HIE.METHODS The study inclusion criteria were determined as the presence of substantial deficit and disability caused by HIE.Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)were intrathecally(IT),intramuscularly(IM),and intravenously administered to participants at a dose of 1×10^(6)/kg for each administration route twice monthly for 2 mo.In different follow-up durations,the effect of WJ-MSCs administration on HIE,the quality of life,prognosis of patients,and side effects were investigated,and patients were evaluated for neurological,cognitive functions,and spasticity using the Wee Functional Independence Measure(Wee FIM)Scale and Modified Ashworth(MA)Scale.RESULTS For all participants(n=6),the mean duration of exposure to hypoxia was 39.17+18.82 min,the mean time interval after HIE was 21.83±26.60 mo,the mean baseline Wee FIM scale score was 13.5±0.55,and the mean baseline MA scale score was 35±9.08.Three patients developed only early complications such as low-grade fever,mild headache associated with IT injection,and muscle pain associated with IM injection,all of which were transient and disappeared within 24 h.The treatment was evaluated to be safe and effective as demonstrated by magnetic resonance imaging examinations,electroencephalographies,laboratory tests,and neurological and functional scores of patients.Patients exhibited significant improvements in all neurological functions through a 12-mo follow-up.The mean Wee FIM scale score of participants increased from 13.5±0.55 to 15.17±1.6 points(mean±SD)at 1 mo(z=-1.826,P=0.068)and to 23.5±3.39 points at 12 mo(z=-2.207,P=0.027)post-treatment.The percentage of patients who achieved an excellent functional improvement(Wee FIM scale total score=126)increased from 10.71%(at baseline)to 12.03%at 1 mo and to 18.65%at 12 mo posttreatment.CONCLUSION Both the triple-route and multiple WJ-MSC implantations were safe and effective in pediatric patients with HIE with significant neurological and functional improvements.The results of this study support conducting further randomized,placebo-controlled studies on this treatment in the pediatric population.展开更多
BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is a leading cause of morbidity and mortality in the adult as well as in the neonate,with limited options for treatment and significant dysfunctionality.AIM To investigat...BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is a leading cause of morbidity and mortality in the adult as well as in the neonate,with limited options for treatment and significant dysfunctionality.AIM To investigate the safety and preliminary efficacy of allogeneic mesenchymal stem cells(MSCs)in HIE patients.METHODS Patients who had HIE for at least 6 mo along with significant dysfunction and disability were included.All patients were given Wharton’s jelly-derived MSCs at 1×106/kg intrathecally,intravenously,and intramuscularly twice a month for two months.The therapeutic effects and prognostic implications of MSCs were evaluated by multiple follow-ups.Functional independence measure(FIM),modified Ashworth,and Karnofsky scales were used to assess any side effects,neurological and cognitive functions,and overall outcomes.RESULTS The 8 subjects included in the study had a mean age of 33.25±10.18 years.Mean HIE exposure and mean post-HIE durations were 45.63±10.18 and 19.67±29.04 mo,respectively.Mean FIM score was 18.38±1.06,mean modified Ashworth score was 43.5±4.63,and mean Karnofsky score was 20.For the first 24 h,5 of the patients experienced a subfebrile state,accompanied by mild headaches due to intrathecally administration and muscle pain because of intramuscularly administration.Neurological and functional examinations,laboratory tests,electroencephalography,and magnetic resonance imaging were performed to assess safety of treatment.Mean FIM score increased by 20.88±3.31 in the first month(P=0.027)and by 31.38±14.69 in 12 mo(P=0.012).The rate of patients with an FIM score of 126 increased from 14.58%to 16.57%in the first month and 24.90%in 12 mo.CONCLUSION Multiple triple-route Wharton’s jelly-derived MSC administrations were found to be safe for HIE patients,indicating neurological and functional improvement.Based on the findings obtained here,further randomized and placebo research could be performed.展开更多
The grading of hypoxic-ischemic encephalopathy(HIE)contributes to the clinical decision making for neonates with HIE.In this paper,an automated grading method based on electroencephalogram(EEG)data is proposed to desc...The grading of hypoxic-ischemic encephalopathy(HIE)contributes to the clinical decision making for neonates with HIE.In this paper,an automated grading method based on electroencephalogram(EEG)data is proposed to describe the severity of HIE infants,namely mild asphyxia,moderate asphyxia and severe asphyxia.The automated grading method is based on a multi-class support vector machine(SVM)classifier,and the input features of SVM classifier include long-term features which are extracted by decomposing the EEG data into different 64 s epoch data and short-term features which are extracted by segmenting the 64 s epoch data into 8 s epoch data with 4 s overlap.Of note,the correlation coefficient and asymmetry extracted in this paper have obvious discriminating capability in HIE infants classification.The experimental results show that the proposed method can achieve the classification accuracy of 78.3%,75.8%and 87.0%of the mild asphyxia group,moderate asphyxia group and severe asphyxia group,respectively.Moreover,the overall accuracy and kappa used to evaluate the performance of the proposed method can reach 79.5%and 0.69,respectively.展开更多
BACKGROUND: It has been proved that brain electrical activity mapping (BEAM) and transcranial Doppler (TCD) detection can reflect the function of brain cell and its diseased degree of infant patients with moderate to ...BACKGROUND: It has been proved that brain electrical activity mapping (BEAM) and transcranial Doppler (TCD) detection can reflect the function of brain cell and its diseased degree of infant patients with moderate to severe hypoxic-ischemic encephalopathy (HIE).OBJECTIVE: To observe the abnormal results of HIE at different degrees detected with BEAM and TCD in infant patients, and compare the detection results at the same time point between BEAM, TCD and computer tomography (CT) examinations.DESIGN: Contrast observation.SETTING: Departments of Neuro-electrophysiology and Pediatrics, Second Affiliated Hospital of Qiqihar Medical College.PARTICIPANTS: Totally 416 infant patients with HIE who received treatment in the Department of Newborn Infants, Second Affiliated Hospital of Qiqihar Medical College during January 2001 and December 2005. The infant patients, 278 male and 138 female, were at embryonic 37 to 42 weeks and weighing 2.0 to 4.1 kg, and they were diagnosed with CT and met the diagnostic criteria of HIE of newborn infants compiled by Department of Neonatology, Pediatric Academy, Chinese Medical Association. According to diagnostic criteria, 130 patients were mild abnormal, 196 moderate abnormal and 90 severe abnormal. The relatives of all the infant patients were informed of the experiment. METHODS: BEAM and TCD examinations were performed in the involved 416 infant patients with HIE at different degrees with DYD2000 16-channel BEAM instrument and EME-2000 ultrasonograph before preliminary diagnosis treatment (within 1 month after birth) and 1,3,6,12 and 24 months after birth, and detected results were compared between BEAM, TCD and CT examinations. MAIN OUTCOME MEASURES: Comparison of detection results of HIE at different time points in infant patients between BEAM, TCD and CT examinations.RESULTS: All the 416 infant patients with HIE participated in the result analysis. ① Comparison of the detected results in infant patients with mild HIE at different time points after birth between BEAM, TCD and CT examinations: BEAM examination showed that the recovery was delayed, and the abnormal rate of BEAM examination was significantly higher than that of CT examination 1 and 3 months after birth [55.4%(72/130)vs. 17.0%(22/130),χ2=41.66;29.2%(38/130) vs. 6.2%(8/130),χ2=23.77,P < 0.01], exceptional patients had mild abnormality and reached the normal level in about 6 months. TCD examination showed that the disease condition significantly improved and infant patients with HIE basically recovered 1 or 2 months after birth, while CT examination showed that infant patients recovered 3 or 4 months after birth. ② Comparison of detection results of infant patients with moderate HIE at different time points between BEAM, TCD and CT examinations: The abnormal rate of BEAM examination was significantly higher than that of CT examination 1,3,6 and 12 months after birth [90.8%(178/196),78.6%(154/196),χ2=4.32,P < 0.05;64.3%(126/196),43.9%(86/196),χ2=16.44;44.9%(88/196),22.4%(44/196),χ2=22.11;21.4%(42/196),10.2%(20/196),χ2=9.27,P < 0.01]. BEAM examination showed that there was still one patient who did not completely recovered in the 24th month due to the relatives of infant patients did not combine the treatment,. TCD examination showed that the abnormal rate was 23.1%(30/196)in the 1st month after birth, and all the patients recovered to the normal in the 3rd month after birth, while CT examination showed that mild abnormality still existed in the 24th month after birth(1.0%,2/196). ③ Comparison of detection results of infant patients with severe HIE at different time points between BEAM, TCD and CT examinations: The abnormal rate of BEAM examination was significantly higher than that of CT examination in the 1st, 3rd, 6th and 12th months after birth[86.7%(78/90),44.4%(40/90),χ2=35.53;62.2%(56/90),31.1%(28/90),χ2=17.51;37.8%(34/90),6.7%(6/90),χ2=27.14,P < 0.01]. BEAM examination showed that mild abnormality still existed in 4 infant patients in the 24th month after birth. TCD examination showed that the abnormal rate was 11.1% (10/90) in the 3rd month after birth, and all the infant patients recovered in the 6th month after birth. CT examination showed that the abnormal rate was 6.7%(6/90) in the 12th month after birth, and all of infant patients recovered to the normal in the 24th month after birth.CONCLUSION: BEAM is the direct index to detect brain function of infant patients with HIE, and positive reaction is still very sensitive in the tracking detection of convalescent period. The positive rate of morphological reaction in CT examination is superior to that in TCD examination, and the positive rate is very high in the acute period of HIE in examination.展开更多
MicroRNA(miRNA)plays a key role in the molecular regulation of neurological diseases,and the molecular mechanism of miRNA is closely related to the occurrence and development of hypoxic-ischemic encephalopathy.Recentl...MicroRNA(miRNA)plays a key role in the molecular regulation of neurological diseases,and the molecular mechanism of miRNA is closely related to the occurrence and development of hypoxic-ischemic encephalopathy.Recently,it has been reported that various miRNA molecules can inhibit target mRNA and even degrade target mRNA by changing the complete complementary or incomplete complementary binding to the target mRNA.Therefore,miRNA is of great significance for the study of mRNA related to hypoxic ischemic encephalopathy.This article briefly reviews the molecular mechanisms,functions and regulation of miRNAs on hypoxic-ischemic encephalopathy.展开更多
BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injur...BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injury, the abnormal functions of brain are varied, and they have very strong plasticity and are corrected easily. OBJECTIVE: To observe the changes of neuronal morphology in hippocampal CA1 region and memory function in newborn rats with hypoxic-ischemic encephalopathy(HIE) from ischemia 6 hours to adult. DESIGN: Completely randomized grouping, controlled experiment. SETTING: Taian Health Center for Women and Children; Taishan Medical College. MATERIALS: Altogether 120 seven-day-old Wistar rats, of clean grade, were provided by the Experimental Animal Center, Shandong University of Traditional Chinese Medicine. Synaptophysin (SYN) polyclonal antibody was provided by Maixin Biological Company, Fuzhou. METHODS: This experiment was carried out in the Laboratory of Morphology, Taishan Medical College between October 2000 and December 2003. ① The newborn rats were randomly divided into 2 groups: model group and control group, 60 rats in each group. Five rats were chosen from each group at postoperative 6 hours, 24 hours, 72 hours, 7 days, 2 weeks and 3 weeks separately for immunohistochemical staining. Fifteen newborn rats were chosen from each group at postoperative 4 weeks and 2 months separately for testing memory ability (After test, 5 rats from each group were sacrificed and used for immunohistochemical staining)② The right common carotid artery of newborn rats of model group was ligated under the anesthetized status. After two hours of incubation, the rats were placed for 2 hours in a container filled with nitrogen oxygen atmosphere containing 0.08 volume fraction of oxygen, thus, HIE models were created; As for the newborn rats in the control group, only blood vessels were isolated, and they were not ligated and hypoxia-treated. ③ Thalamencephal tissue sections of newborn rats of two groups were performed DAB developing and haematoxylin slight staining. Cells with normal nucleous in 250 μm-long granular layer which started from hippocampal CA1 region were counted with image analysis system under high-fold optical microscope (×600), and the thickness of granular layer was measured. The absorbance (A) of positive reactant of SYN in immunohistochemically-stained CA1 region was measured. Learning and memory ability were measured with step through test 3 times successively. ④ t test and paired t test were used for comparing intergroup and intragroup difference of measurement data respectively, and Chi-square for comparing the difference of enumeration data. MAIN OUTCOME MEASURES: Comparison of cytological changes in hippocampal CA1 region and memory ability at different postoperative time points between two groups. RESULTS: Totally 120 newborn rats were involved in the result analysis. ① Cell morphological changes in hippocampal CA1 region: In the control group, with aging, perikaryon, nucleus and nucleolus in cortex of parietal lobe were significantly increased, Nissl body was compacted, the amount of neurons was declined, but the A of SYN positive reactant was relatively increased. In the model group, at postoperative each time point, neurons were seriously shrunk and dark-stained, nucleus was contracted, chromatin was condensed, nucleolus was unclear, even cells disappeared, especially the cells in 6 hours and 24 hours groups. The amount of neurons with normal morphology in hippocampal CA1 region and granular layer thickness in the model group at postoperative each time point were significantly less or smaller than those in the control group at postoperative 6 hours respectively (t =3.002-1.254, P < 0.01). The A value of SYN positive reactant at postoperative 2, 3 and 4 weeks was significantly higher than that at previous time point (t =2.011-2.716,P < 0.05-0.01). ② Test results of learning and memory ability: In the first test, there was no significant difference in the ratio of rats which kept memory ability between two groups (P > 0.05); In the third test, the ratio of rats which kept memory ability in the model group was significantly lower than that in the control group at postoperative 4 weeks and 2 months[53%(8/15),100%(15/15);60%(9/15),93%(14/15),χ 2=2.863,2.901,P < 0.01]. CONCLUSION: The destroyed hippocampal structure induces the decrease of learning and memory ability of developmental rats. Early interference can increase the quality of neurons and also promote functional development of the nervous system.展开更多
Objective To investigate the effect of simple head cooling combined with ganglioside therapy on neonatal hypoxic-ischemic encephalopathy(HIE)and its clinical efficacy.Methods A total of 100 children with HIE admitted ...Objective To investigate the effect of simple head cooling combined with ganglioside therapy on neonatal hypoxic-ischemic encephalopathy(HIE)and its clinical efficacy.Methods A total of 100 children with HIE admitted in the neonatal ward of our hospital from August 2018 to October 2020 were selected as the research objects,and were divided into control group and observation group according to the random number table method,with 50 cases in each group.The control group was treated with gangliosides,and the observation group was treated with simple head cooling combined with gangliosides.Observe and compare the clinical performance improvement time,the level of relevant hematological examination indexes before and after treatment,and the neonatal behavioral neurological assessment(NBNA),clinical efficacy,and adverse reactions.Results The improvement time of convulsions,disturbance of consciousness,pupil changes,hypotonia,and gastrointestinal dysfunction in the observation group was significantly lower than that in the control group(all P<0.001).After treatment,the NSE,IL-6,CK,CK-MB of the two groups of children were significantly lower than before treatment,and the serum calcium and NBNA scores were significantly higher than before treatment,and the decrease or increase in the observation group was significantly higher than that of the control Group(all P<0.001).The total effective rate of treatment of children in the observation group(82.00%)was higher than that of the control group(62.00%)(P<0.05).There were no obvious adverse reactions in both groups.Conclusion The simple head cooling combined with gangliosides in the treatment of HIE can improve the clinical symptoms,blood test index levels,and NBNA scores.The clinical effect is clear and superior to the single use of gangliosides.展开更多
Background Current diagnostic criteria for hypoxic–ischemic encephalopathy in the early hours lack objective measurement tools.Therefore,this systematic review aims to identify putative molecules that can be used in ...Background Current diagnostic criteria for hypoxic–ischemic encephalopathy in the early hours lack objective measurement tools.Therefore,this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice(PROSPERO ID:CRD42021272610).Data sources Searches were performed in PubMed,Web of Science,and Science Direct databases until November 2020.English original papers analyzing samples from newborns>36 weeks that met at least two American College of Obstetricians and Gynecologists diagnostic criteria and/or imaging evidence of cerebral damage were included.Bias was assessed by the Newcastle–Ottawa Scale.The search and data extraction were verified by two authors separately.Results From 373 papers,30 met the inclusion criteria.Data from samples collected in the first 72 hours were extracted,and increased serum levels of neuron-specific enolase and S100-calcium-binding protein-B were associated with a worse prognosis in newborns that suffered an episode of perinatal asphyxia.In addition,the levels of glial fibrillary acidic protein,ubiquitin carboxyl terminal hydrolase isozyme-L1,glutamic pyruvic transaminase-2,lactate,and glucose were elevated in newborns diagnosed with hypoxic–ischemic encephalopathy.Moreover,pathway analysis revealed insulin-like growth factor signaling and alanine,aspartate and glutamate metabolism to be involved in the early molecular response to insult.Conclusions Neuron-specific enolase and S100-calcium-binding protein-B are potential biomarkers,since they are correlated with an unfavorable outcome of hypoxic-ischemic encephalopathy newborns.However,more studies are required to determine the sensitivity and specificity of this approach to be validated for clinical practice.展开更多
Background:Hypoxic-ischemic encephalopathy(HIE)is a devastating condition affecting around 8.5 in 1000 newborns globally.Therapeutic hypothermia(TH)can reduce mortality and,to a limited extent,disability after HIE.Nev...Background:Hypoxic-ischemic encephalopathy(HIE)is a devastating condition affecting around 8.5 in 1000 newborns globally.Therapeutic hypothermia(TH)can reduce mortality and,to a limited extent,disability after HIE.Nevertheless,there is a need for new and effective treatment strategies.Cell-based treatments using mononuclear cells(MNCs),which can be sourced from umbilical cord blood,are currently being investigated.Despite promising preclinical results,there is currently no strong indicator for the clinical efficacy of the approach.This analysis aimed to provide potential explanations for this discrepancy.Methods:A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.Preclinical and clinical studies were retrieved from PubMed,Web of Science,Scopus,and clinicaltrials.gov using a predefined search strategy.A total of 17 preclinical and 7 clinical studies were included.We analyzed overall MNC efficacy in preclinical trials,the methodological quality of preclinical trials,and relevant design features in preclinical versus clinical trials.Results:There was evidence for MNC therapeutic efficacy in preclinical models of HIE.The methodological quality of preclinical studies was not optimal,and statistical design quality was particularly poor.However,methodological quality was above the standard in other fields.There were significant differences in preclinical versus clinical study design including the use of TH as a baseline treatment(only in clinical studies)and much higher MNC doses being applied in preclinical studies.Conclusions:Based on the analyzed data,it is unlikely that therapeutic effect size is massively overestimated in preclinical studies.It is more plausible that the many design differences between preclinical and clinical trials are responsible for the so far lacking proof of the efficacy of MNC treatments in HIE.Additional preclinical and clinical research is required to optimize the application of MNC for experimental HIE treatment.展开更多
Hypoxic-ischemic encephalopathy,which predisposes to neonatal death and neurological sequelae,has a high morbidity,but there is still a lack of effective prevention and treatment in clinical practice.To better underst...Hypoxic-ischemic encephalopathy,which predisposes to neonatal death and neurological sequelae,has a high morbidity,but there is still a lack of effective prevention and treatment in clinical practice.To better understand the pathophysiological mechanism underlying hypoxic-ischemic encephalopathy,in this study we compared hypoxic-ischemic reperfusion brain injury and simple hypoxic-ischemic brain injury in neonatal rats.First,based on the conventional RiceVannucci model of hypoxic-ischemic encephalopathy,we established a rat model of hypoxic-ischemic reperfusion brain injury by creating a common carotid artery muscle bridge.Then we performed tandem mass tag-based proteomic analysis to identify differentially expressed proteins between the hypoxic-ischemic reperfusion brain injury model and the conventional Rice-Vannucci model and found that the majority were mitochondrial proteins.We also performed transmission electron microscopy and found typical characteristics of ferroptosis,including mitochondrial shrinkage,ruptured mitochondrial membranes,and reduced or absent mitochondrial cristae.Further,both rat models showed high levels of glial fibrillary acidic protein and low levels of myelin basic protein,which are biological indicators of hypoxic-ischemic brain injury and indicate similar degrees of damage.Finally,we found that ferroptosis-related Ferritin(Fth1)and glutathione peroxidase 4 were expressed at higher levels in the brain tissue of rats with hypoxic-ischemic reperfusion brain injury than in rats with simple hypoxic-ischemic brain injury.Based on these results,it appears that the rat model of hypoxic-ischemic reperfusion brain injury is more closely related to the pathophysiology of clinical reperfusion.Reperfusion not only aggravates hypoxic-ischemic brain injury but also activates the anti-ferroptosis system.展开更多
In recent years,the increase of psychopathological disorders in the population has become a health emergency,leading to a great effort to understand psychological vulnerability mechanisms.In this scenario,the role of ...In recent years,the increase of psychopathological disorders in the population has become a health emergency,leading to a great effort to understand psychological vulnerability mechanisms.In this scenario,the role of the autonomic nervous system(ANS)has become increasingly important.This study investigated the association between ANS,social skills,and psychopathological functioning in children.As an ANS status proxy,we measured heart rate variability(HRV).Infants admitted to the neonatal intensive care unit of the University Hospital of Padova because of preterm birth or neonatal hypoxic-ischemic encephalopathy were sequentially recruited from January 2011 to June 2013 and followed long-term up to school age in this cross-sectional observational study.We recorded 5 minutes of HRV immediately before measuring performance in social abilities tasks(affect recognition and theory of mind,NEPSY-II)in 50 children(mean age 7.4±1.4 years)with and without risk factors for developing neuropsychiatric disorders due to pre-/perinatal insults without major sequelae.Children also completed extensive cognitive,neuropsychological,and psychosocial assessment.Parents were assessed with psychopathological interviews and a questionnaire(CBCL 6-18).Analysis in a robust Bayesian framework was used to unearth dependencies between HRV,social skills,and psychopathological functioning.Social task scores were associated with HRV components,with high frequency the most consistent.HRV bands were also associated with the psychopathological questionnaire.Only normalized HRV high frequency was able to distinguish impaired children in the affect recognition task.Our data suggest that ANS may be implicated in social cognition both in typical and atypical developmental conditions and that HRV has cross-disease sensitivity.We suggest that HRV parameters may reflect a neurobiological vulnerability to psychopathology.The study was approved by the Ethics Committee of the University Hospital of Padova(Comitato Etico per la Sperimentazione,Azienda Opedaliera di Padova,approval No.1693 P).展开更多
基金supported by the National Natural Science Foundation of China,No.82001604Guizhou Provincial Higher Education Science and Technology Innovation Team,No.[2023]072+1 种基金Guizhou Province Distinguished Young Scientific and Technological Talent Program,No.YQK[2023]040Guizhou Provincial Basic Research Program(Natural Science),No.ZK[2021]-368(all to LXiong),and Zunyi City Innovative Talent Team Training Plan,No.[2022]-2.
文摘Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.
文摘The efficacy and safety of ganglioside in the treatment of neonates who suffer from hypoxic-ischemic encephalopathy(HIE)needs to be fully evaluated.We searched the following databases:PubMed,ScienceDirect,LISTA,CNKI,Chinese biomedical literature database and Wanfang digital journals of full-text database to determine the inclusion and exclusion criteria of papers and a total of 12 papers were included after quality evaluation.Then we conducted the meta-analysis with RevMan5.0 software.The results showed that compared with the control group,the abnormal rate declined in the ganglioside-treated group(relative risk(RR)=0.27,95%confidence interval(CI)=0.05-1.96).NBNA records of the 7,10-14d neonates were improved effectively:RR(95%CI)were 2.28(0.86-3.42)and 2.53(1.04-2.92)respectively.Neural system sequelae incidence was reduced significantly:RR(95%CI)=0.35:(0.15-0.79).Ganglioside treatment could effectively reduce the abnormality rate of head size,improve the neurological score,reduce the incidence of neurological sequelae,and significantly prompt clinical recovery for neonates with HIE.
文摘BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is one of the leading causes of death and long-term neurological impairment in the pediatric population.Despite a limited number of treatments to cure HIE,stem cell therapies appear to be a potential treatment option for brain injury resulting from HIE.AIM To investigate the efficacy and safety of stem cell-based therapies in pediatric patients with HIE.METHODS The study inclusion criteria were determined as the presence of substantial deficit and disability caused by HIE.Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)were intrathecally(IT),intramuscularly(IM),and intravenously administered to participants at a dose of 1×10^(6)/kg for each administration route twice monthly for 2 mo.In different follow-up durations,the effect of WJ-MSCs administration on HIE,the quality of life,prognosis of patients,and side effects were investigated,and patients were evaluated for neurological,cognitive functions,and spasticity using the Wee Functional Independence Measure(Wee FIM)Scale and Modified Ashworth(MA)Scale.RESULTS For all participants(n=6),the mean duration of exposure to hypoxia was 39.17+18.82 min,the mean time interval after HIE was 21.83±26.60 mo,the mean baseline Wee FIM scale score was 13.5±0.55,and the mean baseline MA scale score was 35±9.08.Three patients developed only early complications such as low-grade fever,mild headache associated with IT injection,and muscle pain associated with IM injection,all of which were transient and disappeared within 24 h.The treatment was evaluated to be safe and effective as demonstrated by magnetic resonance imaging examinations,electroencephalographies,laboratory tests,and neurological and functional scores of patients.Patients exhibited significant improvements in all neurological functions through a 12-mo follow-up.The mean Wee FIM scale score of participants increased from 13.5±0.55 to 15.17±1.6 points(mean±SD)at 1 mo(z=-1.826,P=0.068)and to 23.5±3.39 points at 12 mo(z=-2.207,P=0.027)post-treatment.The percentage of patients who achieved an excellent functional improvement(Wee FIM scale total score=126)increased from 10.71%(at baseline)to 12.03%at 1 mo and to 18.65%at 12 mo posttreatment.CONCLUSION Both the triple-route and multiple WJ-MSC implantations were safe and effective in pediatric patients with HIE with significant neurological and functional improvements.The results of this study support conducting further randomized,placebo-controlled studies on this treatment in the pediatric population.
文摘BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is a leading cause of morbidity and mortality in the adult as well as in the neonate,with limited options for treatment and significant dysfunctionality.AIM To investigate the safety and preliminary efficacy of allogeneic mesenchymal stem cells(MSCs)in HIE patients.METHODS Patients who had HIE for at least 6 mo along with significant dysfunction and disability were included.All patients were given Wharton’s jelly-derived MSCs at 1×106/kg intrathecally,intravenously,and intramuscularly twice a month for two months.The therapeutic effects and prognostic implications of MSCs were evaluated by multiple follow-ups.Functional independence measure(FIM),modified Ashworth,and Karnofsky scales were used to assess any side effects,neurological and cognitive functions,and overall outcomes.RESULTS The 8 subjects included in the study had a mean age of 33.25±10.18 years.Mean HIE exposure and mean post-HIE durations were 45.63±10.18 and 19.67±29.04 mo,respectively.Mean FIM score was 18.38±1.06,mean modified Ashworth score was 43.5±4.63,and mean Karnofsky score was 20.For the first 24 h,5 of the patients experienced a subfebrile state,accompanied by mild headaches due to intrathecally administration and muscle pain because of intramuscularly administration.Neurological and functional examinations,laboratory tests,electroencephalography,and magnetic resonance imaging were performed to assess safety of treatment.Mean FIM score increased by 20.88±3.31 in the first month(P=0.027)and by 31.38±14.69 in 12 mo(P=0.012).The rate of patients with an FIM score of 126 increased from 14.58%to 16.57%in the first month and 24.90%in 12 mo.CONCLUSION Multiple triple-route Wharton’s jelly-derived MSC administrations were found to be safe for HIE patients,indicating neurological and functional improvement.Based on the findings obtained here,further randomized and placebo research could be performed.
基金Natural Science Foundation of Zhejiang Province(grant numbers LGG19F030013 and LGF18F010007)Special Funds for Information Development in Shanghai(grant number 201801050)Scientific research project of Zhejiang Provincial Department of Education(grant number Y201942165).
文摘The grading of hypoxic-ischemic encephalopathy(HIE)contributes to the clinical decision making for neonates with HIE.In this paper,an automated grading method based on electroencephalogram(EEG)data is proposed to describe the severity of HIE infants,namely mild asphyxia,moderate asphyxia and severe asphyxia.The automated grading method is based on a multi-class support vector machine(SVM)classifier,and the input features of SVM classifier include long-term features which are extracted by decomposing the EEG data into different 64 s epoch data and short-term features which are extracted by segmenting the 64 s epoch data into 8 s epoch data with 4 s overlap.Of note,the correlation coefficient and asymmetry extracted in this paper have obvious discriminating capability in HIE infants classification.The experimental results show that the proposed method can achieve the classification accuracy of 78.3%,75.8%and 87.0%of the mild asphyxia group,moderate asphyxia group and severe asphyxia group,respectively.Moreover,the overall accuracy and kappa used to evaluate the performance of the proposed method can reach 79.5%and 0.69,respectively.
文摘BACKGROUND: It has been proved that brain electrical activity mapping (BEAM) and transcranial Doppler (TCD) detection can reflect the function of brain cell and its diseased degree of infant patients with moderate to severe hypoxic-ischemic encephalopathy (HIE).OBJECTIVE: To observe the abnormal results of HIE at different degrees detected with BEAM and TCD in infant patients, and compare the detection results at the same time point between BEAM, TCD and computer tomography (CT) examinations.DESIGN: Contrast observation.SETTING: Departments of Neuro-electrophysiology and Pediatrics, Second Affiliated Hospital of Qiqihar Medical College.PARTICIPANTS: Totally 416 infant patients with HIE who received treatment in the Department of Newborn Infants, Second Affiliated Hospital of Qiqihar Medical College during January 2001 and December 2005. The infant patients, 278 male and 138 female, were at embryonic 37 to 42 weeks and weighing 2.0 to 4.1 kg, and they were diagnosed with CT and met the diagnostic criteria of HIE of newborn infants compiled by Department of Neonatology, Pediatric Academy, Chinese Medical Association. According to diagnostic criteria, 130 patients were mild abnormal, 196 moderate abnormal and 90 severe abnormal. The relatives of all the infant patients were informed of the experiment. METHODS: BEAM and TCD examinations were performed in the involved 416 infant patients with HIE at different degrees with DYD2000 16-channel BEAM instrument and EME-2000 ultrasonograph before preliminary diagnosis treatment (within 1 month after birth) and 1,3,6,12 and 24 months after birth, and detected results were compared between BEAM, TCD and CT examinations. MAIN OUTCOME MEASURES: Comparison of detection results of HIE at different time points in infant patients between BEAM, TCD and CT examinations.RESULTS: All the 416 infant patients with HIE participated in the result analysis. ① Comparison of the detected results in infant patients with mild HIE at different time points after birth between BEAM, TCD and CT examinations: BEAM examination showed that the recovery was delayed, and the abnormal rate of BEAM examination was significantly higher than that of CT examination 1 and 3 months after birth [55.4%(72/130)vs. 17.0%(22/130),χ2=41.66;29.2%(38/130) vs. 6.2%(8/130),χ2=23.77,P < 0.01], exceptional patients had mild abnormality and reached the normal level in about 6 months. TCD examination showed that the disease condition significantly improved and infant patients with HIE basically recovered 1 or 2 months after birth, while CT examination showed that infant patients recovered 3 or 4 months after birth. ② Comparison of detection results of infant patients with moderate HIE at different time points between BEAM, TCD and CT examinations: The abnormal rate of BEAM examination was significantly higher than that of CT examination 1,3,6 and 12 months after birth [90.8%(178/196),78.6%(154/196),χ2=4.32,P < 0.05;64.3%(126/196),43.9%(86/196),χ2=16.44;44.9%(88/196),22.4%(44/196),χ2=22.11;21.4%(42/196),10.2%(20/196),χ2=9.27,P < 0.01]. BEAM examination showed that there was still one patient who did not completely recovered in the 24th month due to the relatives of infant patients did not combine the treatment,. TCD examination showed that the abnormal rate was 23.1%(30/196)in the 1st month after birth, and all the patients recovered to the normal in the 3rd month after birth, while CT examination showed that mild abnormality still existed in the 24th month after birth(1.0%,2/196). ③ Comparison of detection results of infant patients with severe HIE at different time points between BEAM, TCD and CT examinations: The abnormal rate of BEAM examination was significantly higher than that of CT examination in the 1st, 3rd, 6th and 12th months after birth[86.7%(78/90),44.4%(40/90),χ2=35.53;62.2%(56/90),31.1%(28/90),χ2=17.51;37.8%(34/90),6.7%(6/90),χ2=27.14,P < 0.01]. BEAM examination showed that mild abnormality still existed in 4 infant patients in the 24th month after birth. TCD examination showed that the abnormal rate was 11.1% (10/90) in the 3rd month after birth, and all the infant patients recovered in the 6th month after birth. CT examination showed that the abnormal rate was 6.7%(6/90) in the 12th month after birth, and all of infant patients recovered to the normal in the 24th month after birth.CONCLUSION: BEAM is the direct index to detect brain function of infant patients with HIE, and positive reaction is still very sensitive in the tracking detection of convalescent period. The positive rate of morphological reaction in CT examination is superior to that in TCD examination, and the positive rate is very high in the acute period of HIE in examination.
基金National Natural Science Foundation of China(No.30671803,81273174)National University Student Innovation and Entrepreneurship Project(No.201810222013)
文摘MicroRNA(miRNA)plays a key role in the molecular regulation of neurological diseases,and the molecular mechanism of miRNA is closely related to the occurrence and development of hypoxic-ischemic encephalopathy.Recently,it has been reported that various miRNA molecules can inhibit target mRNA and even degrade target mRNA by changing the complete complementary or incomplete complementary binding to the target mRNA.Therefore,miRNA is of great significance for the study of mRNA related to hypoxic ischemic encephalopathy.This article briefly reviews the molecular mechanisms,functions and regulation of miRNAs on hypoxic-ischemic encephalopathy.
基金the Grant from Family Planning Commission of Shandong Province,No.97-15
文摘BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injury, the abnormal functions of brain are varied, and they have very strong plasticity and are corrected easily. OBJECTIVE: To observe the changes of neuronal morphology in hippocampal CA1 region and memory function in newborn rats with hypoxic-ischemic encephalopathy(HIE) from ischemia 6 hours to adult. DESIGN: Completely randomized grouping, controlled experiment. SETTING: Taian Health Center for Women and Children; Taishan Medical College. MATERIALS: Altogether 120 seven-day-old Wistar rats, of clean grade, were provided by the Experimental Animal Center, Shandong University of Traditional Chinese Medicine. Synaptophysin (SYN) polyclonal antibody was provided by Maixin Biological Company, Fuzhou. METHODS: This experiment was carried out in the Laboratory of Morphology, Taishan Medical College between October 2000 and December 2003. ① The newborn rats were randomly divided into 2 groups: model group and control group, 60 rats in each group. Five rats were chosen from each group at postoperative 6 hours, 24 hours, 72 hours, 7 days, 2 weeks and 3 weeks separately for immunohistochemical staining. Fifteen newborn rats were chosen from each group at postoperative 4 weeks and 2 months separately for testing memory ability (After test, 5 rats from each group were sacrificed and used for immunohistochemical staining)② The right common carotid artery of newborn rats of model group was ligated under the anesthetized status. After two hours of incubation, the rats were placed for 2 hours in a container filled with nitrogen oxygen atmosphere containing 0.08 volume fraction of oxygen, thus, HIE models were created; As for the newborn rats in the control group, only blood vessels were isolated, and they were not ligated and hypoxia-treated. ③ Thalamencephal tissue sections of newborn rats of two groups were performed DAB developing and haematoxylin slight staining. Cells with normal nucleous in 250 μm-long granular layer which started from hippocampal CA1 region were counted with image analysis system under high-fold optical microscope (×600), and the thickness of granular layer was measured. The absorbance (A) of positive reactant of SYN in immunohistochemically-stained CA1 region was measured. Learning and memory ability were measured with step through test 3 times successively. ④ t test and paired t test were used for comparing intergroup and intragroup difference of measurement data respectively, and Chi-square for comparing the difference of enumeration data. MAIN OUTCOME MEASURES: Comparison of cytological changes in hippocampal CA1 region and memory ability at different postoperative time points between two groups. RESULTS: Totally 120 newborn rats were involved in the result analysis. ① Cell morphological changes in hippocampal CA1 region: In the control group, with aging, perikaryon, nucleus and nucleolus in cortex of parietal lobe were significantly increased, Nissl body was compacted, the amount of neurons was declined, but the A of SYN positive reactant was relatively increased. In the model group, at postoperative each time point, neurons were seriously shrunk and dark-stained, nucleus was contracted, chromatin was condensed, nucleolus was unclear, even cells disappeared, especially the cells in 6 hours and 24 hours groups. The amount of neurons with normal morphology in hippocampal CA1 region and granular layer thickness in the model group at postoperative each time point were significantly less or smaller than those in the control group at postoperative 6 hours respectively (t =3.002-1.254, P < 0.01). The A value of SYN positive reactant at postoperative 2, 3 and 4 weeks was significantly higher than that at previous time point (t =2.011-2.716,P < 0.05-0.01). ② Test results of learning and memory ability: In the first test, there was no significant difference in the ratio of rats which kept memory ability between two groups (P > 0.05); In the third test, the ratio of rats which kept memory ability in the model group was significantly lower than that in the control group at postoperative 4 weeks and 2 months[53%(8/15),100%(15/15);60%(9/15),93%(14/15),χ 2=2.863,2.901,P < 0.01]. CONCLUSION: The destroyed hippocampal structure induces the decrease of learning and memory ability of developmental rats. Early interference can increase the quality of neurons and also promote functional development of the nervous system.
基金Natural Science Foundation of Anhui Province(1808085MH308)School Research Fund Project of Anhui Medical University(2019xkj178)Hefei Science and Technology Research Project(J2018Y06)。
文摘Objective To investigate the effect of simple head cooling combined with ganglioside therapy on neonatal hypoxic-ischemic encephalopathy(HIE)and its clinical efficacy.Methods A total of 100 children with HIE admitted in the neonatal ward of our hospital from August 2018 to October 2020 were selected as the research objects,and were divided into control group and observation group according to the random number table method,with 50 cases in each group.The control group was treated with gangliosides,and the observation group was treated with simple head cooling combined with gangliosides.Observe and compare the clinical performance improvement time,the level of relevant hematological examination indexes before and after treatment,and the neonatal behavioral neurological assessment(NBNA),clinical efficacy,and adverse reactions.Results The improvement time of convulsions,disturbance of consciousness,pupil changes,hypotonia,and gastrointestinal dysfunction in the observation group was significantly lower than that in the control group(all P<0.001).After treatment,the NSE,IL-6,CK,CK-MB of the two groups of children were significantly lower than before treatment,and the serum calcium and NBNA scores were significantly higher than before treatment,and the decrease or increase in the observation group was significantly higher than that of the control Group(all P<0.001).The total effective rate of treatment of children in the observation group(82.00%)was higher than that of the control group(62.00%)(P<0.05).There were no obvious adverse reactions in both groups.Conclusion The simple head cooling combined with gangliosides in the treatment of HIE can improve the clinical symptoms,blood test index levels,and NBNA scores.The clinical effect is clear and superior to the single use of gangliosides.
基金funding provided by FCT|FCCN(b-on)financed by the European Regional Development Fund(ERDF),through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization and Portuguese national funds via FCT-Fundcao para a Ciencia e a Tecnologia,under projects POCI-01-0145-FEDER-029311,POCI-01-0247-FEDER-045311,UIDB/04539/2020 and UIDP/04539/2020individual Ph.D.fellowships PD/BD/135178/2017(Margarida Coelho),SFRH/BD/143442/2019(Ines Caramelo),and 2020.07749.BD(Miguel Rosado).
文摘Background Current diagnostic criteria for hypoxic–ischemic encephalopathy in the early hours lack objective measurement tools.Therefore,this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice(PROSPERO ID:CRD42021272610).Data sources Searches were performed in PubMed,Web of Science,and Science Direct databases until November 2020.English original papers analyzing samples from newborns>36 weeks that met at least two American College of Obstetricians and Gynecologists diagnostic criteria and/or imaging evidence of cerebral damage were included.Bias was assessed by the Newcastle–Ottawa Scale.The search and data extraction were verified by two authors separately.Results From 373 papers,30 met the inclusion criteria.Data from samples collected in the first 72 hours were extracted,and increased serum levels of neuron-specific enolase and S100-calcium-binding protein-B were associated with a worse prognosis in newborns that suffered an episode of perinatal asphyxia.In addition,the levels of glial fibrillary acidic protein,ubiquitin carboxyl terminal hydrolase isozyme-L1,glutamic pyruvic transaminase-2,lactate,and glucose were elevated in newborns diagnosed with hypoxic–ischemic encephalopathy.Moreover,pathway analysis revealed insulin-like growth factor signaling and alanine,aspartate and glutamate metabolism to be involved in the early molecular response to insult.Conclusions Neuron-specific enolase and S100-calcium-binding protein-B are potential biomarkers,since they are correlated with an unfavorable outcome of hypoxic-ischemic encephalopathy newborns.However,more studies are required to determine the sensitivity and specificity of this approach to be validated for clinical practice.
基金Academy of Medical Sciences(Newton Advanced Fellowship),Grant/Award Number:NAF\R11\1010。
文摘Background:Hypoxic-ischemic encephalopathy(HIE)is a devastating condition affecting around 8.5 in 1000 newborns globally.Therapeutic hypothermia(TH)can reduce mortality and,to a limited extent,disability after HIE.Nevertheless,there is a need for new and effective treatment strategies.Cell-based treatments using mononuclear cells(MNCs),which can be sourced from umbilical cord blood,are currently being investigated.Despite promising preclinical results,there is currently no strong indicator for the clinical efficacy of the approach.This analysis aimed to provide potential explanations for this discrepancy.Methods:A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.Preclinical and clinical studies were retrieved from PubMed,Web of Science,Scopus,and clinicaltrials.gov using a predefined search strategy.A total of 17 preclinical and 7 clinical studies were included.We analyzed overall MNC efficacy in preclinical trials,the methodological quality of preclinical trials,and relevant design features in preclinical versus clinical trials.Results:There was evidence for MNC therapeutic efficacy in preclinical models of HIE.The methodological quality of preclinical studies was not optimal,and statistical design quality was particularly poor.However,methodological quality was above the standard in other fields.There were significant differences in preclinical versus clinical study design including the use of TH as a baseline treatment(only in clinical studies)and much higher MNC doses being applied in preclinical studies.Conclusions:Based on the analyzed data,it is unlikely that therapeutic effect size is massively overestimated in preclinical studies.It is more plausible that the many design differences between preclinical and clinical trials are responsible for the so far lacking proof of the efficacy of MNC treatments in HIE.Additional preclinical and clinical research is required to optimize the application of MNC for experimental HIE treatment.
基金supported by the National Natural Science Foundation of China,No.82271747(to ZLL)Medical and Health Science and Technology Program of Zhejiang Province of China,No.2023RC048(to WL)。
文摘Hypoxic-ischemic encephalopathy,which predisposes to neonatal death and neurological sequelae,has a high morbidity,but there is still a lack of effective prevention and treatment in clinical practice.To better understand the pathophysiological mechanism underlying hypoxic-ischemic encephalopathy,in this study we compared hypoxic-ischemic reperfusion brain injury and simple hypoxic-ischemic brain injury in neonatal rats.First,based on the conventional RiceVannucci model of hypoxic-ischemic encephalopathy,we established a rat model of hypoxic-ischemic reperfusion brain injury by creating a common carotid artery muscle bridge.Then we performed tandem mass tag-based proteomic analysis to identify differentially expressed proteins between the hypoxic-ischemic reperfusion brain injury model and the conventional Rice-Vannucci model and found that the majority were mitochondrial proteins.We also performed transmission electron microscopy and found typical characteristics of ferroptosis,including mitochondrial shrinkage,ruptured mitochondrial membranes,and reduced or absent mitochondrial cristae.Further,both rat models showed high levels of glial fibrillary acidic protein and low levels of myelin basic protein,which are biological indicators of hypoxic-ischemic brain injury and indicate similar degrees of damage.Finally,we found that ferroptosis-related Ferritin(Fth1)and glutathione peroxidase 4 were expressed at higher levels in the brain tissue of rats with hypoxic-ischemic reperfusion brain injury than in rats with simple hypoxic-ischemic brain injury.Based on these results,it appears that the rat model of hypoxic-ischemic reperfusion brain injury is more closely related to the pathophysiology of clinical reperfusion.Reperfusion not only aggravates hypoxic-ischemic brain injury but also activates the anti-ferroptosis system.
文摘In recent years,the increase of psychopathological disorders in the population has become a health emergency,leading to a great effort to understand psychological vulnerability mechanisms.In this scenario,the role of the autonomic nervous system(ANS)has become increasingly important.This study investigated the association between ANS,social skills,and psychopathological functioning in children.As an ANS status proxy,we measured heart rate variability(HRV).Infants admitted to the neonatal intensive care unit of the University Hospital of Padova because of preterm birth or neonatal hypoxic-ischemic encephalopathy were sequentially recruited from January 2011 to June 2013 and followed long-term up to school age in this cross-sectional observational study.We recorded 5 minutes of HRV immediately before measuring performance in social abilities tasks(affect recognition and theory of mind,NEPSY-II)in 50 children(mean age 7.4±1.4 years)with and without risk factors for developing neuropsychiatric disorders due to pre-/perinatal insults without major sequelae.Children also completed extensive cognitive,neuropsychological,and psychosocial assessment.Parents were assessed with psychopathological interviews and a questionnaire(CBCL 6-18).Analysis in a robust Bayesian framework was used to unearth dependencies between HRV,social skills,and psychopathological functioning.Social task scores were associated with HRV components,with high frequency the most consistent.HRV bands were also associated with the psychopathological questionnaire.Only normalized HRV high frequency was able to distinguish impaired children in the affect recognition task.Our data suggest that ANS may be implicated in social cognition both in typical and atypical developmental conditions and that HRV has cross-disease sensitivity.We suggest that HRV parameters may reflect a neurobiological vulnerability to psychopathology.The study was approved by the Ethics Committee of the University Hospital of Padova(Comitato Etico per la Sperimentazione,Azienda Opedaliera di Padova,approval No.1693 P).
