Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal medicine.Preterm encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts ...Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal medicine.Preterm encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a lifetime.The cost of disability associated with preterm brain injury continues to rise.Prevention of this injury,and disability,would significantly reduce this socioeconomic burden.展开更多
We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome(DPHLS),also known as Grinker’s myelinopathy,is a rare but significant neurological condition that manifests days to weeks after a hypoxic event.Characteriz...BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome(DPHLS),also known as Grinker’s myelinopathy,is a rare but significant neurological condition that manifests days to weeks after a hypoxic event.Characterized by delayed onset of neurological and cognitive deficits,DPHLS presents substantial diagnostic and therapeutic challenges.AIM To consolidate current knowledge on pathophysiology,clinical features,diagnostic approaches,and management strategies for DPHLS,providing a comprehensive overview and highlighting gaps for future research.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines,we systematically searched PubMed,ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy.Inclusion criteria were original research articles,case reports,and case series involving human subjects with detailed clinical,neuroimaging,or pathological data on DPHLS.Data were extracted on study characteristics,participant demographics,clinical features,neuroimaging findings,pathological findings,treatment,and outcomes.The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist.RESULTS A total of 73 cases were reviewed.Common comorbidities included schizoaffective disorder,bipolar disorder,hypertension,and substance use disorder.The primary causes of hypoxia were benzodiazepine overdose,opioid overdose,polysubstance overdose,and carbon monoxide(CO)poisoning.Symptoms frequently include decreased level of consciousness,psychomotor agitation,cognitive decline,parkinsonism,and encephalopathy.Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter,sometimes involving the basal ganglia and the globus pallidus.Magnetic resonance spectroscopy often showed decreased N-acetylaspartate,elevated choline,choline-to-creatinine ratio,and normal or elevated lactate.Treatment is often supportive,including amantadine,an antioxidant cocktail,and steroids.Hyperbaric oxygen therapy may be beneficial in those with CO poisoning.Parkinsonism was often treated with levodopa.Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits.CONCLUSION DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations.Early recognition and appropriate management are crucial to improving patient outcomes.Future research should focus on standardizing diagnostic criteria,using advanced imaging techniques,and exploring therapeutic interventions to improve understanding and treatment of DPHLS.Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.展开更多
Background: Moderate to severe hypoxic-ischemic encephalopathy (HIE) in neonates is often treated with hypothermia. However, some neonates may experience epileptic seizures during therapeutic hypothermia (TH). Data on...Background: Moderate to severe hypoxic-ischemic encephalopathy (HIE) in neonates is often treated with hypothermia. However, some neonates may experience epileptic seizures during therapeutic hypothermia (TH). Data on the electrophysiologic and evolutionary aspects of these seizures are scarce in African countries. Objectives: To determine the types of epileptic seizures caused by HIE in neonates in Brazzaville;to describe the evolution of background EEG activities during TH and rewarming;to report the evolution of epileptic seizures. Methods: This was a cross-sectional, descriptive study conducted from January 2020 to July 2022. It took place in Brazzaville in the Neonatology Department of the Blanche Gomez Mother and Child Hospital. It focused on term neonates suffering from moderate or severe HIE. They were treated with hypothermia combined with phenobarbital for 72 hours. Results: Among 36 neonates meeting inclusion criteria, there were 18 boys and 18 girls. Thirty-one (86.1%) neonates had grade 2 and 5 (13.9%) grade 3 HIE. In our neonates, HIE had induced isolated electrographic seizures (n = 11;30.6%), electroclinical seizures (n = 25;69.4%), and 6 types of background EEG activity. During TH and rewarming, there were 52.8% of patients with improved background EEG activity, 41.7% of patients with unchanged background EEG activity, and 5.5% of patients with worsened background EEG activity. At the end of rewarming, only 9 (25%) patients still had seizures. Conclusion: Isolated electrographic and electroclinical seizures are the only pathological entities found in our studied population. In neonates with moderate HIE, the applied therapeutic strategy positively influences the evolution of both seizures and background EEG activity. On the other hand, in neonates with severe HIE, the same therapeutic strategy is ineffective. .展开更多
Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases rema...Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases remain poorly understood. In this study, we recruited 14 termborn infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children's Hospital, China. Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups. However, compared with the mild hypoxic ischemic encephalopathy group, the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient. The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group. Moreover, nodal efficiency was reduced in the left rolandic operculum, left supramarginal gyrus, bilateral superior temporal gyrus, and right middle temporal gyrus. These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy, and may be associated with impaired language, motion, and cognition. These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy, enabling early interventions targeting brain function. This study was approved by the Regional Ethics Review Boards of the Changzhou Children's Hospital(approval No. 2013-001) on January 31, 2013. Informed consent was obtained from the family members of the children. The trial was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR1800016409) and the protocol version is 1.0.展开更多
Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability.Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;ho...Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability.Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;however,many infants still experience lifelong disabilities to movement,sensation and cognition.Clinical guidelines,based on strong clinical and preclinical evidence,recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours,with a target brain temperature of 33.5 ±0.5℃ for infants with moderate to severe hypoxic-ischemic encephalopathy.The clinical guidelines also recommend that infants be re warmed at a rate of 0.5℃ per hour,but this is not based on strong evidence.There are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic encephalopathy.Preclinical studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of hypothermia.In this review,we evaluate the evidence for the optimal start time,duration and depth of hypothermia,and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.展开更多
Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild ...Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild hypothermia (27-28~C) can increase the survival rate of neural stem cells (1.0 x 105/~tL) transplanted into neonatal mice with hypoxic-ischemic encephalopathy. Long-term effects on neurological functioning of the mice were also examined. After mild hy- pothermia combined with neural stem cell transplantation, we observed decreased expression levels of inflammatory factor nuclear factor-kappa B and apoptotic factor caspase-3, reduced cerebral infarct volumes, increased survival rate of transplanted cells, and marked improvements in neurological function. Thus, the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation are superior to those of monotherapy. Moreover, our findings suggest that the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation on hypoxic-ischemic encephalopathy are achieved by anti-inflammatory and an- ti-apoptotic mechanisms.展开更多
Lesions of the brainstem have been reported in the clinical scenarios of hypoxic-ischemic encephalopathy(HIE), although the prevalence of these lesions is probably underestimated. Neuropathologic studies have demonstr...Lesions of the brainstem have been reported in the clinical scenarios of hypoxic-ischemic encephalopathy(HIE), although the prevalence of these lesions is probably underestimated. Neuropathologic studies have demonstrated brainstem involvement in severely asphyxiated infants as an indicator of poor outcome. Among survivors to HIE, the most frequent clinical complaints that may be predicted by brainstem lesions include feeding problems, speech, language and communication problems and visual impairments. Clinical series, including vascular and metabolic etiologies, have found selective involvement of the brainstem with the demonstration of symmetric bilateral columnar lesions of the tegmentum. The role of brainstem lesions in HIE is currently a matter of debate, especially when tegmental lesions are present in the absence of supratentorial lesions. Differential diagnosis of tegmental lesions in neonates and infants include congenital metabolic syndromes and drug-related processes. Brainstem injury with the presence of supratentorial lesions is a predictor of poor outcome and high rates of mortality and morbidity. Further investigation will be conducted to identify specific sites of the brainstem that are vulnerable to hypoxic-ischemic and toxic-metabolic insults.展开更多
Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one of the most promis...Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one of the most promising neuroprotective agents.We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment.In this study,41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group(hypothermia alone for 72 hours,n = 20) and erythropoietin group(hypothermia + erythropoietin 200 IU/kg for 10 days,n = 21).Our results show that compared with the control group,serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days.However,neurodevelopmental outcome was similar between the two groups at 9 months of age.These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.展开更多
It has been reported that early intervention of hyperbaric oxygen (HBO) can promote the intellectual rehabilitation of infants with severe hypoxic-ischemic encephalopathy (HIE) and can prevent mental retardation r...It has been reported that early intervention of hyperbaric oxygen (HBO) can promote the intellectual rehabilitation of infants with severe hypoxic-ischemic encephalopathy (HIE) and can prevent mental retardation recently. However, the prior observations on the therapeutic effect almost were short-term. How about the observations on prospective efficacy and the following up on systematic intelligence test? OBJECTIVE: To investigate the short-term and long-term effects of HBO therapy on the promotion of the intellectual rehabilitation in infants with severe HIE. DESIGN: A comparative observation. SETTING: Department of Pediatrics, Affiliated Hospital, Qingdao University Medical College. PARTICIPANTS: Forty-seven infants with severe HIE (35 males and 12 females) were treated with HBO in the Department of Pediatrics, the Affiliated Hospital of the Medical College of Qingdao University from October 1996 to July 1999. All of them were consistent with the diagnostic criteria and clinical grading on severe HIE which were designed by Chinese Medical Association pediatrics committee neonate group in Hangzhou, October, 1996. Informed contents were obtained from the relatives of all the infants. METHODS: ① Grouping: The infants were randomly divided into two groups according to the order of admission, those of odd numbers were HBO group (n =24) and those of even numbers were control group (n =23). All the infants were treated with routine therapy for 3 months, in addition to HBO therapy in the HBO group, once a day for 4 courses of l0 days with the interval of l0 - 15 days since 8 to l0 days after birth. HBO chamber produced by the 701 Institute of China Ship Industry Company was used, and the therapy pressure was 0.14- 0.16 MPa, and the time of compression and decompression were both 15 minutes while voltage-stabilizing was 30 minutes. ② In order to evaluate the short-term and long-term effects of HBO on intellectual rehabilitation in infants with HIE, neonatal behavioral neurological assessment (NBNA) was employed at 7 and 28 days after birth, and Bayley scale of infant development (BSID) was got at two years old in both groups, as well as Wechsler preschool and primary scale of intelligence (WPPSI) at five years. MAIN OUTCOME MEASURES: Comparison of short-term and long-term intelligence between the two groups. RESULTS: ① Results of NBNA: The NBNA score at 28 days was significantly higher in the HBO group than in the control group (P 〈 0.01). ② Results of BSID: The score of mental development index (MDI) of BSID at two years old in the HBO group was significantly higher than that in the control group (P 〈 0.05). ③ Results of WPPSI: The score of full-scale intelligence quotient (FIQ) and verbal intelligence quotient (VIQ) of WPPSI in the HBO group were significantly higher than those in the control group (P 〈 0.05). In addition, the rate of mental retardation in the HBO group was significantly lower than that in the control group [12.5% (3/24), 39.1%(9/23), P 〈 0.05]. CONCLUSION: Not only the short-term intellectual rehabilitation but also the long-term one in infants with severe HIE could be promoted by HBO therapy, which might be benefit to the prevention of mental retardation.展开更多
Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of ...Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of thioperamide during brain edema in a rat model of neonatal hypoxic ischemic encephalopathy. Our results showed that thioperamide significantly decreased brain water content and malondialdehyde levels, while significantly increased histamine levels and superoxide dismutase activity in the hippocampus. This evidence demonstrates that thioperamide could pre vent oxidative damage and attenuate brain edema following neonatal hypoxicischemic encepha Iopathy. We further observed that changes in the above indexes occurred after combined treatment of thioperamide with the H1 receptor antagonist, pyrilamine, and the H2 receptor antagonist, ci metidine. Experimental findings indicated that pyrilamine reversed the effects of thioperamide; however, cimetidine had no significant influence on the effects of thioperamide. Our present findings suggest that thioperamide can increase brain histamine content and attenuate brain edema and oxidative damage by acting in combination with postsynaptic H1 receptors in a rat model of neo natal hypoxicischemic encephalopathy.展开更多
Hypoxic-ischemic encephalopathy(HIE) is a disease that occurs when the brain is subjected to hypoxia,resulting in neuronal death and neurological deficits,with a poor prognosis.The mechanisms underlying hypoxic-isch...Hypoxic-ischemic encephalopathy(HIE) is a disease that occurs when the brain is subjected to hypoxia,resulting in neuronal death and neurological deficits,with a poor prognosis.The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release,cellular proteolysis,reactive oxygen species generation,nitric oxide synthesis,and inflammation.The molecular and cellular changes in HIE include protein misfolding,aggregation,and destruction of organelles.The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway,the extrinsic Fas receptor pathway,and the endoplasmic reticulum stress-induced pathway.Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century.Hypothermia,xenon gas treatment,the use of melatonin and erythropoietin,and hypoxic-ischemic preconditioning have proven effective in HIE patients.Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes.A large number of molecular chaperones are induced after brain ischemia and hypoxia,among which the heat shock proteins are the most important.Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects.Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations,assisting in the proper folding of newly synthesized polypeptides,regulating the degradation of misfolded proteins,inhibiting the aggregation of proteins,and by controlling the refolding of misfolded proteins.In addition,heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways,including the intrinsic pathway,the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway.Molecular chaperones play a key role in neuroprotection in HIE.In this review,we provide an overview of the mechanisms of HIE and discuss the various treatment strategies.Given their critical role in the disease,molecular chaperones are promising therapeutic targets for HIE.展开更多
Ginsenoside Rgl is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether ne...Ginsenoside Rgl is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10-80 ~tM ginsenoside Rgl. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rgl had the greatest differentiation-inducing effect and was the concentration used for subsequent exper- iments. Whole-cell patch clamp showed that neural stem cells induced by 20 jaM ginsenoside Rgl were more mature than non-induced cells. We then established neonatal rat models of hypox- ic-ischemic encephalopathy using the suture method, and ginsenoside Rgl-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rgl-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.展开更多
Introduction: Neonatal asphyxia is a major cause of infant morbidity in Cameroon. The aim of this study was to describe the short-term neurological outcome of children following neonatal Hypoxic-ischemic encephalopath...Introduction: Neonatal asphyxia is a major cause of infant morbidity in Cameroon. The aim of this study was to describe the short-term neurological outcome of children following neonatal Hypoxic-ischemic encephalopathy (HIE). Methodology: We conducted a retrospective cohort study from May 2010 to September 2013. We included 39 exposed cases against 78 non-exposed cases followed-up for at least 9 months. The variables studied were: age, sex, head circumference, neurological sequelae, postural anomalies and motor skills and developmental age/quotient. The data collected were analyzed using Epi info software version 3.5.3. The Fisher Exact Test was used to compare the variables with a significance threshold defined for p Results: We recruited 39 cases for 78 controls. The majority (74.40%) of cases were classified as HIE Sarnat 3 and 25.60% Sarnat 2. Most of the children were aged 12 - 36 months with a mean age of 18 months. The male sex was predominant with a sex ratio of 1.2;and 61.50% of children with HIE had head circumference Conclusion: The frequency of neurological sequelae following HIE was high in our series. Efforts should be made to prevent perinatal asphyxia and to ensure the availability of material and staff trained to help babies’ breath in all the delivery rooms in our maternities.展开更多
Objective To study the changes of the nitric oxide(NO) in process of neonate hypoxic- ischemic encephalopathy(HIE) and the relations between the concentrations of NO and HIE. Methods Tested the concentrations of NO i...Objective To study the changes of the nitric oxide(NO) in process of neonate hypoxic- ischemic encephalopathy(HIE) and the relations between the concentrations of NO and HIE. Methods Tested the concentrations of NO in CSF of newborn infants suffered HIE the third day and in plasma of newborn infants suffered HIE just attacked instant(within 2 hours), the first day ,the third day and restoring stage and compared with them of normal contrast term. We tried to analyse the reasons and significance of NO change .Results The NO concentration is the highest in plasma of newborn infants suffered HIE the first day. There is significant difference(P<0.01) after comparing the NO concentrations in plasmas of newborn infants suffered HIE just attacked instant, the first day, the third day with of normal contrast team respectively. But there is not significant difference(P >0.05) between NO in plasmas of restoring stage and of normal contrast team. There is positive correlation between the NO concentration in plasma and in CSF of newborn infants suffered HIE the third day. The more serious the disease is, the higher the NO concentration is, the worse the prognosis is. Conclusion NO play along with the course of HIE and play an important role in neonate HIE. Testing the concentration of NO in plasma and in CSF can also help to judge the degree of disease.展开更多
Objective:To explore the effects of mild hypothermia combined EPO therapy on cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy. Methods: A total of 72 children with HI...Objective:To explore the effects of mild hypothermia combined EPO therapy on cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy. Methods: A total of 72 children with HIE who were diagnosed and treated in the hospital between December 2015 and June 2017 were chosen as the study subjects and divided into control group (n=36) and EPO group (n=36) by random number table method. Control group received mild hypothermia therapy on the basis of conventional therapy, and EPO group received EPO therapy on the basis of the therapy for control group. The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were compared between the two groups before and after treatment.Results: The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were not statistically significant between the two groups before treatment. After the treatment ended, serum cerebral injury indexes VILIP-1, NPY and NSE levels of EPO group were lower than those of control group whereas IGF-1 level was higher than that of control group;myocardial injury indexes CT-1, Myo and cTnⅠ levels were lower than those of control group;oxidative stress indexes GSH-Px and SOD levels were higher than those of control group whereas AOPP and ROS levels were lower than those of control group.Conclusion: Mild hypothermia combined with EPO therapy can improve the cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy.展开更多
In order to study the changes of nitric oxide (NO) in gastric wall in hy-poxic neonatal rats, the activity of nitric oxide synthase (NOS) of gastric wall was measured and the NADPH-diaphorase biochemistry test was tak...In order to study the changes of nitric oxide (NO) in gastric wall in hy-poxic neonatal rats, the activity of nitric oxide synthase (NOS) of gastric wall was measured and the NADPH-diaphorase biochemistry test was taken to show the distribution of NOS in the gastric wall of neonatal rats. The results showed that compared with normal rats, NOS had no significant changes in the acute hy-poxic rats (P>0. 05). However, in hypoxic-ischemic encephalopathy (HIE) neonatal rats, the activity of NOS was markedly increased (P<0. 01), and the NOS positive reactive products were markedly increased in the gastric muscle, but no changes in the mucosal and submucosal layers were observed. The results suggest that the decreased gastric motivation and the gastric mucosal lesions caused by asphyxia are associated with the changes of NO in gastric wall.展开更多
Objective:To study the evaluation value of the quantitative electroencephalogram (qEEG) for the prognosis of neonatal hypoxic ischemic encephalopathy (HIE) and its relationship with serological indicators.Methods: 76 ...Objective:To study the evaluation value of the quantitative electroencephalogram (qEEG) for the prognosis of neonatal hypoxic ischemic encephalopathy (HIE) and its relationship with serological indicators.Methods: 76 children with HIE who were born and treated in our hospital between April 2013 and February 2017 were collected as observation group, and 50 healthy newborns who were born in our hospital during the same period were collected as normal control group. qEEG parameter values of two groups of children were determined, serum levels of nerve injury indexes, nerve apoptosis indexes and oxidative stress indexes were compared between the two groups, and Pearson test was used to evaluate the inner link between qEEG parameter values and disease severity in children with HIE.Results: qEEG Fp1, Fp2, C3, C4, T3, T4, O1 and O2 loci power spectrum values of observation group were significantly lower than those of normal control group. Serum NSE, NPY, S-100B and MBP contents in observation group were higher than those in normal control group;nerve apoptosis indexes sFas, sFasL and Caspase-3 contents were higher than those in normal control group while Bcl-2 content was lower than that in normal control group;serum oxidative stress indexes AOPP and MDA contents were higher than those in normal control group while SOD content was lower than that in normal control group. Pearson test showed that qEEG Fp1, Fp2, C3, C4, T3, T4, O1 and O2 loci power spectrum values in children with HIE were directly correlated with the contents of nerve injury indexes, nerve apoptosis indexes and oxidative stress indexes. Conclusion: The qEEG parameter values in children with HIE are lower than those in normal children, and the specific values are closely related to the severity of the disease.展开更多
Hypoxic-ischemic brain injury models were generated by bilateral carotid artery ligation in Sprague-Dawley rats. Successful models were treated with a combination of Xuefuzhuyu decoction and 10g of astragalus. The exp...Hypoxic-ischemic brain injury models were generated by bilateral carotid artery ligation in Sprague-Dawley rats. Successful models were treated with a combination of Xuefuzhuyu decoction and 10g of astragalus. The experimental results showed that neuronal morphology and structure recovered, nerve growth factor mRNA expression increased in brain tissues, and neurological function signifi-cantly improved. There was no significant difference in these measures compared with rats treated with Xuefuzhuyu decoction alone or a combined treatment of Xuefuzhuyu decoction with 40 g as-tragalus. These experimental findings revealed that, Xuefuzhuyu decoction combined with astra-galus may up-regulate the expression of nerve growth factor mRNA and accordingly exert a neu-roprotective effect; however, this protection is not dependent on astragalus dosage.展开更多
Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential ...Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2'-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2'- deoxyuddine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.展开更多
基金This work was supported by Health Research Council of New Zealand(grants 17/601 and 22/559)the Auckland Medical Research Foundation,the Lottery Health Grants Board of New Zealand,the C.J.Martin Postdoctoral Fellowship and project grant from the National Health and Medical Research Council of Australia(APP1090890 and APP1164954)the Victorian Government’s Operational Infrastructure Support Program(to RG).
文摘Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal medicine.Preterm encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a lifetime.The cost of disability associated with preterm brain injury continues to rise.Prevention of this injury,and disability,would significantly reduce this socioeconomic burden.
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
文摘BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome(DPHLS),also known as Grinker’s myelinopathy,is a rare but significant neurological condition that manifests days to weeks after a hypoxic event.Characterized by delayed onset of neurological and cognitive deficits,DPHLS presents substantial diagnostic and therapeutic challenges.AIM To consolidate current knowledge on pathophysiology,clinical features,diagnostic approaches,and management strategies for DPHLS,providing a comprehensive overview and highlighting gaps for future research.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines,we systematically searched PubMed,ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy.Inclusion criteria were original research articles,case reports,and case series involving human subjects with detailed clinical,neuroimaging,or pathological data on DPHLS.Data were extracted on study characteristics,participant demographics,clinical features,neuroimaging findings,pathological findings,treatment,and outcomes.The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist.RESULTS A total of 73 cases were reviewed.Common comorbidities included schizoaffective disorder,bipolar disorder,hypertension,and substance use disorder.The primary causes of hypoxia were benzodiazepine overdose,opioid overdose,polysubstance overdose,and carbon monoxide(CO)poisoning.Symptoms frequently include decreased level of consciousness,psychomotor agitation,cognitive decline,parkinsonism,and encephalopathy.Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter,sometimes involving the basal ganglia and the globus pallidus.Magnetic resonance spectroscopy often showed decreased N-acetylaspartate,elevated choline,choline-to-creatinine ratio,and normal or elevated lactate.Treatment is often supportive,including amantadine,an antioxidant cocktail,and steroids.Hyperbaric oxygen therapy may be beneficial in those with CO poisoning.Parkinsonism was often treated with levodopa.Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits.CONCLUSION DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations.Early recognition and appropriate management are crucial to improving patient outcomes.Future research should focus on standardizing diagnostic criteria,using advanced imaging techniques,and exploring therapeutic interventions to improve understanding and treatment of DPHLS.Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.
文摘Background: Moderate to severe hypoxic-ischemic encephalopathy (HIE) in neonates is often treated with hypothermia. However, some neonates may experience epileptic seizures during therapeutic hypothermia (TH). Data on the electrophysiologic and evolutionary aspects of these seizures are scarce in African countries. Objectives: To determine the types of epileptic seizures caused by HIE in neonates in Brazzaville;to describe the evolution of background EEG activities during TH and rewarming;to report the evolution of epileptic seizures. Methods: This was a cross-sectional, descriptive study conducted from January 2020 to July 2022. It took place in Brazzaville in the Neonatology Department of the Blanche Gomez Mother and Child Hospital. It focused on term neonates suffering from moderate or severe HIE. They were treated with hypothermia combined with phenobarbital for 72 hours. Results: Among 36 neonates meeting inclusion criteria, there were 18 boys and 18 girls. Thirty-one (86.1%) neonates had grade 2 and 5 (13.9%) grade 3 HIE. In our neonates, HIE had induced isolated electrographic seizures (n = 11;30.6%), electroclinical seizures (n = 25;69.4%), and 6 types of background EEG activity. During TH and rewarming, there were 52.8% of patients with improved background EEG activity, 41.7% of patients with unchanged background EEG activity, and 5.5% of patients with worsened background EEG activity. At the end of rewarming, only 9 (25%) patients still had seizures. Conclusion: Isolated electrographic and electroclinical seizures are the only pathological entities found in our studied population. In neonates with moderate HIE, the applied therapeutic strategy positively influences the evolution of both seizures and background EEG activity. On the other hand, in neonates with severe HIE, the same therapeutic strategy is ineffective. .
基金supported by the Jiangsu Maternal and Child Health Research Project of China,No.F201612(to HXL)Changzhou Science and Technology Support Plan of China,No.CE20165027(to HXL)+1 种基金Changzhou City Planning Commission Major Science and Technology Projects of China,No.ZD201515(to HXL)Changzhou High Level Training Fund for Health Professionals of China,No.2016CZBJ028(to HXL)
文摘Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases remain poorly understood. In this study, we recruited 14 termborn infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children's Hospital, China. Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups. However, compared with the mild hypoxic ischemic encephalopathy group, the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient. The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group. Moreover, nodal efficiency was reduced in the left rolandic operculum, left supramarginal gyrus, bilateral superior temporal gyrus, and right middle temporal gyrus. These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy, and may be associated with impaired language, motion, and cognition. These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy, enabling early interventions targeting brain function. This study was approved by the Regional Ethics Review Boards of the Changzhou Children's Hospital(approval No. 2013-001) on January 31, 2013. Informed consent was obtained from the family members of the children. The trial was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR1800016409) and the protocol version is 1.0.
基金supported by The Health Research Council of New Zealand(grant No.16/003,17/601)the Marsden Fund(grant No.17-UOA232)a Sir Charles Hercus Fellowship from the Health Research Council of New Zealand(grant No.16/003)
文摘Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability.Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;however,many infants still experience lifelong disabilities to movement,sensation and cognition.Clinical guidelines,based on strong clinical and preclinical evidence,recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours,with a target brain temperature of 33.5 ±0.5℃ for infants with moderate to severe hypoxic-ischemic encephalopathy.The clinical guidelines also recommend that infants be re warmed at a rate of 0.5℃ per hour,but this is not based on strong evidence.There are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic encephalopathy.Preclinical studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of hypothermia.In this review,we evaluate the evidence for the optimal start time,duration and depth of hypothermia,and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.
基金supported by the National Natural Science Foundation of China,No.81271382
文摘Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild hypothermia (27-28~C) can increase the survival rate of neural stem cells (1.0 x 105/~tL) transplanted into neonatal mice with hypoxic-ischemic encephalopathy. Long-term effects on neurological functioning of the mice were also examined. After mild hy- pothermia combined with neural stem cell transplantation, we observed decreased expression levels of inflammatory factor nuclear factor-kappa B and apoptotic factor caspase-3, reduced cerebral infarct volumes, increased survival rate of transplanted cells, and marked improvements in neurological function. Thus, the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation are superior to those of monotherapy. Moreover, our findings suggest that the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation on hypoxic-ischemic encephalopathy are achieved by anti-inflammatory and an- ti-apoptotic mechanisms.
文摘Lesions of the brainstem have been reported in the clinical scenarios of hypoxic-ischemic encephalopathy(HIE), although the prevalence of these lesions is probably underestimated. Neuropathologic studies have demonstrated brainstem involvement in severely asphyxiated infants as an indicator of poor outcome. Among survivors to HIE, the most frequent clinical complaints that may be predicted by brainstem lesions include feeding problems, speech, language and communication problems and visual impairments. Clinical series, including vascular and metabolic etiologies, have found selective involvement of the brainstem with the demonstration of symmetric bilateral columnar lesions of the tegmentum. The role of brainstem lesions in HIE is currently a matter of debate, especially when tegmental lesions are present in the absence of supratentorial lesions. Differential diagnosis of tegmental lesions in neonates and infants include congenital metabolic syndromes and drug-related processes. Brainstem injury with the presence of supratentorial lesions is a predictor of poor outcome and high rates of mortality and morbidity. Further investigation will be conducted to identify specific sites of the brainstem that are vulnerable to hypoxic-ischemic and toxic-metabolic insults.
基金supported by a grant from the Health and Family Planning Commission of Hebei Province of China,No.20150033a grant from the Science and Technology Research and Development Project of Handan City of Hebei Province of China,No.152810879-6
文摘Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one of the most promising neuroprotective agents.We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment.In this study,41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group(hypothermia alone for 72 hours,n = 20) and erythropoietin group(hypothermia + erythropoietin 200 IU/kg for 10 days,n = 21).Our results show that compared with the control group,serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days.However,neurodevelopmental outcome was similar between the two groups at 9 months of age.These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.
文摘It has been reported that early intervention of hyperbaric oxygen (HBO) can promote the intellectual rehabilitation of infants with severe hypoxic-ischemic encephalopathy (HIE) and can prevent mental retardation recently. However, the prior observations on the therapeutic effect almost were short-term. How about the observations on prospective efficacy and the following up on systematic intelligence test? OBJECTIVE: To investigate the short-term and long-term effects of HBO therapy on the promotion of the intellectual rehabilitation in infants with severe HIE. DESIGN: A comparative observation. SETTING: Department of Pediatrics, Affiliated Hospital, Qingdao University Medical College. PARTICIPANTS: Forty-seven infants with severe HIE (35 males and 12 females) were treated with HBO in the Department of Pediatrics, the Affiliated Hospital of the Medical College of Qingdao University from October 1996 to July 1999. All of them were consistent with the diagnostic criteria and clinical grading on severe HIE which were designed by Chinese Medical Association pediatrics committee neonate group in Hangzhou, October, 1996. Informed contents were obtained from the relatives of all the infants. METHODS: ① Grouping: The infants were randomly divided into two groups according to the order of admission, those of odd numbers were HBO group (n =24) and those of even numbers were control group (n =23). All the infants were treated with routine therapy for 3 months, in addition to HBO therapy in the HBO group, once a day for 4 courses of l0 days with the interval of l0 - 15 days since 8 to l0 days after birth. HBO chamber produced by the 701 Institute of China Ship Industry Company was used, and the therapy pressure was 0.14- 0.16 MPa, and the time of compression and decompression were both 15 minutes while voltage-stabilizing was 30 minutes. ② In order to evaluate the short-term and long-term effects of HBO on intellectual rehabilitation in infants with HIE, neonatal behavioral neurological assessment (NBNA) was employed at 7 and 28 days after birth, and Bayley scale of infant development (BSID) was got at two years old in both groups, as well as Wechsler preschool and primary scale of intelligence (WPPSI) at five years. MAIN OUTCOME MEASURES: Comparison of short-term and long-term intelligence between the two groups. RESULTS: ① Results of NBNA: The NBNA score at 28 days was significantly higher in the HBO group than in the control group (P 〈 0.01). ② Results of BSID: The score of mental development index (MDI) of BSID at two years old in the HBO group was significantly higher than that in the control group (P 〈 0.05). ③ Results of WPPSI: The score of full-scale intelligence quotient (FIQ) and verbal intelligence quotient (VIQ) of WPPSI in the HBO group were significantly higher than those in the control group (P 〈 0.05). In addition, the rate of mental retardation in the HBO group was significantly lower than that in the control group [12.5% (3/24), 39.1%(9/23), P 〈 0.05]. CONCLUSION: Not only the short-term intellectual rehabilitation but also the long-term one in infants with severe HIE could be promoted by HBO therapy, which might be benefit to the prevention of mental retardation.
基金supported by Jilin Provincial Science and Technology Department Foundation ofChina, No. 200905134
文摘Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of thioperamide during brain edema in a rat model of neonatal hypoxic ischemic encephalopathy. Our results showed that thioperamide significantly decreased brain water content and malondialdehyde levels, while significantly increased histamine levels and superoxide dismutase activity in the hippocampus. This evidence demonstrates that thioperamide could pre vent oxidative damage and attenuate brain edema following neonatal hypoxicischemic encepha Iopathy. We further observed that changes in the above indexes occurred after combined treatment of thioperamide with the H1 receptor antagonist, pyrilamine, and the H2 receptor antagonist, ci metidine. Experimental findings indicated that pyrilamine reversed the effects of thioperamide; however, cimetidine had no significant influence on the effects of thioperamide. Our present findings suggest that thioperamide can increase brain histamine content and attenuate brain edema and oxidative damage by acting in combination with postsynaptic H1 receptors in a rat model of neo natal hypoxicischemic encephalopathy.
文摘Hypoxic-ischemic encephalopathy(HIE) is a disease that occurs when the brain is subjected to hypoxia,resulting in neuronal death and neurological deficits,with a poor prognosis.The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release,cellular proteolysis,reactive oxygen species generation,nitric oxide synthesis,and inflammation.The molecular and cellular changes in HIE include protein misfolding,aggregation,and destruction of organelles.The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway,the extrinsic Fas receptor pathway,and the endoplasmic reticulum stress-induced pathway.Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century.Hypothermia,xenon gas treatment,the use of melatonin and erythropoietin,and hypoxic-ischemic preconditioning have proven effective in HIE patients.Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes.A large number of molecular chaperones are induced after brain ischemia and hypoxia,among which the heat shock proteins are the most important.Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects.Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations,assisting in the proper folding of newly synthesized polypeptides,regulating the degradation of misfolded proteins,inhibiting the aggregation of proteins,and by controlling the refolding of misfolded proteins.In addition,heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways,including the intrinsic pathway,the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway.Molecular chaperones play a key role in neuroprotection in HIE.In this review,we provide an overview of the mechanisms of HIE and discuss the various treatment strategies.Given their critical role in the disease,molecular chaperones are promising therapeutic targets for HIE.
基金supported by the Natural Science Foundation of Chongqing in China,No.CSTC2011jj A0013
文摘Ginsenoside Rgl is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10-80 ~tM ginsenoside Rgl. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rgl had the greatest differentiation-inducing effect and was the concentration used for subsequent exper- iments. Whole-cell patch clamp showed that neural stem cells induced by 20 jaM ginsenoside Rgl were more mature than non-induced cells. We then established neonatal rat models of hypox- ic-ischemic encephalopathy using the suture method, and ginsenoside Rgl-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rgl-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.
文摘Introduction: Neonatal asphyxia is a major cause of infant morbidity in Cameroon. The aim of this study was to describe the short-term neurological outcome of children following neonatal Hypoxic-ischemic encephalopathy (HIE). Methodology: We conducted a retrospective cohort study from May 2010 to September 2013. We included 39 exposed cases against 78 non-exposed cases followed-up for at least 9 months. The variables studied were: age, sex, head circumference, neurological sequelae, postural anomalies and motor skills and developmental age/quotient. The data collected were analyzed using Epi info software version 3.5.3. The Fisher Exact Test was used to compare the variables with a significance threshold defined for p Results: We recruited 39 cases for 78 controls. The majority (74.40%) of cases were classified as HIE Sarnat 3 and 25.60% Sarnat 2. Most of the children were aged 12 - 36 months with a mean age of 18 months. The male sex was predominant with a sex ratio of 1.2;and 61.50% of children with HIE had head circumference Conclusion: The frequency of neurological sequelae following HIE was high in our series. Efforts should be made to prevent perinatal asphyxia and to ensure the availability of material and staff trained to help babies’ breath in all the delivery rooms in our maternities.
基金Foundation:Guangdong province board of health item (number 199906)
文摘Objective To study the changes of the nitric oxide(NO) in process of neonate hypoxic- ischemic encephalopathy(HIE) and the relations between the concentrations of NO and HIE. Methods Tested the concentrations of NO in CSF of newborn infants suffered HIE the third day and in plasma of newborn infants suffered HIE just attacked instant(within 2 hours), the first day ,the third day and restoring stage and compared with them of normal contrast term. We tried to analyse the reasons and significance of NO change .Results The NO concentration is the highest in plasma of newborn infants suffered HIE the first day. There is significant difference(P<0.01) after comparing the NO concentrations in plasmas of newborn infants suffered HIE just attacked instant, the first day, the third day with of normal contrast team respectively. But there is not significant difference(P >0.05) between NO in plasmas of restoring stage and of normal contrast team. There is positive correlation between the NO concentration in plasma and in CSF of newborn infants suffered HIE the third day. The more serious the disease is, the higher the NO concentration is, the worse the prognosis is. Conclusion NO play along with the course of HIE and play an important role in neonate HIE. Testing the concentration of NO in plasma and in CSF can also help to judge the degree of disease.
文摘Objective:To explore the effects of mild hypothermia combined EPO therapy on cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy. Methods: A total of 72 children with HIE who were diagnosed and treated in the hospital between December 2015 and June 2017 were chosen as the study subjects and divided into control group (n=36) and EPO group (n=36) by random number table method. Control group received mild hypothermia therapy on the basis of conventional therapy, and EPO group received EPO therapy on the basis of the therapy for control group. The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were compared between the two groups before and after treatment.Results: The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were not statistically significant between the two groups before treatment. After the treatment ended, serum cerebral injury indexes VILIP-1, NPY and NSE levels of EPO group were lower than those of control group whereas IGF-1 level was higher than that of control group;myocardial injury indexes CT-1, Myo and cTnⅠ levels were lower than those of control group;oxidative stress indexes GSH-Px and SOD levels were higher than those of control group whereas AOPP and ROS levels were lower than those of control group.Conclusion: Mild hypothermia combined with EPO therapy can improve the cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy.
文摘In order to study the changes of nitric oxide (NO) in gastric wall in hy-poxic neonatal rats, the activity of nitric oxide synthase (NOS) of gastric wall was measured and the NADPH-diaphorase biochemistry test was taken to show the distribution of NOS in the gastric wall of neonatal rats. The results showed that compared with normal rats, NOS had no significant changes in the acute hy-poxic rats (P>0. 05). However, in hypoxic-ischemic encephalopathy (HIE) neonatal rats, the activity of NOS was markedly increased (P<0. 01), and the NOS positive reactive products were markedly increased in the gastric muscle, but no changes in the mucosal and submucosal layers were observed. The results suggest that the decreased gastric motivation and the gastric mucosal lesions caused by asphyxia are associated with the changes of NO in gastric wall.
文摘Objective:To study the evaluation value of the quantitative electroencephalogram (qEEG) for the prognosis of neonatal hypoxic ischemic encephalopathy (HIE) and its relationship with serological indicators.Methods: 76 children with HIE who were born and treated in our hospital between April 2013 and February 2017 were collected as observation group, and 50 healthy newborns who were born in our hospital during the same period were collected as normal control group. qEEG parameter values of two groups of children were determined, serum levels of nerve injury indexes, nerve apoptosis indexes and oxidative stress indexes were compared between the two groups, and Pearson test was used to evaluate the inner link between qEEG parameter values and disease severity in children with HIE.Results: qEEG Fp1, Fp2, C3, C4, T3, T4, O1 and O2 loci power spectrum values of observation group were significantly lower than those of normal control group. Serum NSE, NPY, S-100B and MBP contents in observation group were higher than those in normal control group;nerve apoptosis indexes sFas, sFasL and Caspase-3 contents were higher than those in normal control group while Bcl-2 content was lower than that in normal control group;serum oxidative stress indexes AOPP and MDA contents were higher than those in normal control group while SOD content was lower than that in normal control group. Pearson test showed that qEEG Fp1, Fp2, C3, C4, T3, T4, O1 and O2 loci power spectrum values in children with HIE were directly correlated with the contents of nerve injury indexes, nerve apoptosis indexes and oxidative stress indexes. Conclusion: The qEEG parameter values in children with HIE are lower than those in normal children, and the specific values are closely related to the severity of the disease.
基金a grant by Bureau of Traditional Chinese Medicine of Zhejiang Province, No.491040-W50434
文摘Hypoxic-ischemic brain injury models were generated by bilateral carotid artery ligation in Sprague-Dawley rats. Successful models were treated with a combination of Xuefuzhuyu decoction and 10g of astragalus. The experimental results showed that neuronal morphology and structure recovered, nerve growth factor mRNA expression increased in brain tissues, and neurological function signifi-cantly improved. There was no significant difference in these measures compared with rats treated with Xuefuzhuyu decoction alone or a combined treatment of Xuefuzhuyu decoction with 40 g as-tragalus. These experimental findings revealed that, Xuefuzhuyu decoction combined with astra-galus may up-regulate the expression of nerve growth factor mRNA and accordingly exert a neu-roprotective effect; however, this protection is not dependent on astragalus dosage.
基金supported by Guangdong Province Science Research Project,No.B30502
文摘Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2'-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2'- deoxyuddine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.