Ischemic Encephalopathy Research Articles

METTL3 inhibits microglial pyroptosis in neonatal hypoxia-ischemia encephalopathy by regulating GPR39 expression in an m6A-HuR-dependent manner

BackgroundNeonatal hypoxia–ischemia encephalopathy (HIE) is a significant reason for neonatal mortality and prolonged disability. We have previously revealed that GPR39 activation attenuates neuroinflammation in a neonatal HIE rat model. This study aimed to investigate whether GPR39 affected microglial pyroptosis post-HIE. MethodsA neonatal rat model of HIE and a microglia cell model of oxygen-glucose deprivation (OGD) were established. Neuronal loss and cerebral infarction were assessed by using TTC, H&E staining, and Nissl staining. Pyroptosis was evaluated with western blot, LDH assay kit, ELISA, and flow cytometry. Total m6A level and GPR39 m6A modification were determined using m6A dot blot and MeRIP. The interaction between METTL3/HuR/GSK3β and GPR39 was analyzed by performing molecular interaction experiments. GPR39 mRNA stability was examined with actinomycin D. ResultsThe level of GPR39 was increased in neonatal HIE rats and OGD-treated microglia. Brain injury and neuronal loss were significantly increased in the HIE model when GPR39 was knocked down. GPR39 knockdown aggravated NLRP3 inflammasome-mediated microglial pyroptosis. METTL3 upregulated GPR39 expression in an m6A-dependent manner. METTL3 enhanced the interaction of HuR and GPR39. In OGD-exposed microglia, METTL3 elevated GPR39 expression and mRNA stability, which declined after HuR depletion. METTL3 knockdown promoted microglial pyroptosis, which was reversed by GPR39 agonist. Furthermore, microglial pyroptosis was inhibited by GPR39 upregulation, but the outcome was reverted by GSK3β activator SNP. ConclusionMETTL3 inhibits microglial pyroptosis in neonatal HIE via regulating m6A-HuR dependent stabilization of GPR39, which contributes to therapeutics development for neonatal HIE.

Time to recovery of asphyxiated neonates and its’ predictors among newborns admitted to neonatal intensive care unit at Debre Berhan Comprehensive Specialized Hospital, Ethiopia

BackgroundNeonatal asphyxia is a leading cause of early neonatal mortality, accounting for approximately 900,000 deaths each year. Assessing survival rates, recovery time and predictors of mortality among asphyxiated neonates can help policymakers design, implement, and evaluate programs to achieve the sustainable development goal of reducing neonatal mortality to 12/1,000 live births by 2030. The current study sought to ascertain the survival status, recovery time, and predictors of neonatal asphyxia.MethodsA retrospective follow-up study conducted in Debre Berhan Comprehensive Specialized Hospital, which carried out from May 20th to June 20th, 2023 using records of asphyxiated babies in NICUs from January 1st, 2020 to December 31st, 2022, involving a sample size of 330. Pre-structured questionnaires created in Google Form were used to collect data, and STATA Version 14.0 was utilized for data entry and analysis, respectively. The Kaplan–Meier survival curve, log rank test, and median time were calculated. A multivariable Cox proportional hazards regression model was fitted in order to determine the predictors of time to recovery. Variables were statistically significant if their p-value was less than 0.05.ResultsThree hundred thirty admitted asphyxiated neonates were followed a total of 2706 neonate -days with a minimum of 1 day to 18 days. The overall incidence density rate of survival was 9.9 per 100 neonates’ days of observation (95% CI: 8.85–11.24) with a median recovery time of 9 days (95% CI: 0.82–0.93). Prolonged labor (Adjusted hazard ratio (AHR: 0.42,95%CI:0.21–0.81), normal birth weight (AHR:2.21,95% CI: 1.30–3.70),non-altered consciousness (AHR:2.52,CI:1.50–4.24),non-depressed moro reflex of the newborn (AHR:2.40,95%CI: 1.03–5.61), stage I HIE (AHR: 5.11,95% CI: 1.98–13.19),and direct oxygen administration via the nose (AHR: 4.18,95% CI: 2.21–7.89) were found to be independent predictors of time to recovery of asphyxiated neonates..ConclusionIn the current findings, the recovery time was prolonged compared to other findings. This implies early diagnosis, strict monitoring and provision of appropriate measures timely is necessary before the babies complicated into the highest stage of hypoxic –ischemic encephalopathy(HIE) and managing complications are the recommended to hasten recovery time and increase the survival of neonates.

Umbilical cord blood stem cells: transplantation prospects in neurological practice

Umbilical cord blood has evolved from being considered a mere cellular/tissue waste product after childbirth to a valuable biological material with a wide regenerative potential. Today, hematopoietic cord blood stem cells are used in the same way as bone marrow and mobilised peripheral blood as part of the standard medical treatment for haemoblastoses and hereditary blood diseases. There is an increasing amount of experimental data showing possibility of umbilical cord blood cell fractions using for treatment of non-hematological diseases and, in particular, diseases of the central nervous system. One of the key challenges in cell therapy for central nervous system diseases is the choice of cellular material for neurotransplantation. This is particularly relevant for ischemic and traumatic injuries, as well as neurodegenerative diseases. Stem or mature somatic cells prepared for neurotransplantation should have predictable and reproducible characteristics thataccording therapeutic purposes, exactly: trophic and/or neuroprotective action to increase neurons viability in damaged area; axon growth stimulation and myelination; cell matrix restoration or predictable differentiation direction to replace amount of lost brain or spinal cord cells. The fact that umbilical cord blood contains not only hematopoietic, but also various non-hematopoietic stem cells with a wide regenerative potential has become the basis for active use of these cells for neurotransplantation. The proposed review provides historical information about umbilical cord blood introduction into practical medicine, its cellular composition and clinical applications of stem cells various types for children central nervous system diseases treatment, such as ischemic encephalopathy, stroke, cerebral hemorrhage, cerebral palsy, autism, and in adults — for stroke treatment, spinal cord injury and neurodegenerative diseases.

PP-041 Hypoxic and ischemic encephalopathy: current situation in Tunisia, a descriptive and analytical multicenter study

PP-041 Hypoxic and ischemic encephalopathy: current situation in Tunisia, a descriptive and analytical multicenter study

Risk Factors for Deranged Renal Function in Term Asphyxiated Newborn Babies: A Cross-sectional Study

Introduction: Perinatal asphyxia is a significant cause of morbidity and mortality in the Neonatal Intensive Care Unit (NICU). As the kidneys are very sensitive to hypoxia, renal insufficiency can occur within 24 hours of a hypoxic insult and may lead to irreversible injury. Aim: To evaluate risk factors for impaired renal function in term asphyxiated newborn babies in a tertiary care hospital located in Central India. Materials and Methods: A cross-sectional observational study was conducted in the Neonatal Intensive Care Unit (NICU), IGGMC and Mayo Hospital, Nagpur, Maharashtra, Central India, from October 2020 to September 2022. A total of 95 term neonates with perinatal asphyxia were enrolled. Risk factors were noted, urine output was recorded, and neonates were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury Network (AKIN) criteria. Data were tabulated and statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) software version 21.0 to determine the significance of each risk factor for AKI. Continuous variables were compared using the unpaired t-test or Mann-Whitney U Test (when datasets were not normally distributed). Categorical variables were compared using the Chi-square test or Fisher’s-exact test. Results: Out of 95 neonates, comprising 53 males and 42 females with a mean gestational age of 38.6 weeks in the AKI group and 34 weeks in the non AKI group, 58 (61.1%) had AKI; 15 (25.86%) were AKI stage 1, 28 (48.27%) were AKI stage 2, and 15 (25.86%) were AKI stage 3. Among the risk factors, significant perinatal risk factors included Meconium-Stained Liquor (MSL) (p-value=0.0252), oligohydramnios (p-value=0.0246), prolonged labour (p-value=0.0276), and endotracheal tube (ETT) intubation as a mode of resuscitation (p-value=0.0008). Maternal risk factors such as Gestational Diabetes Mellitus (GDM) (p-value=0.0488) and Pregnancy-induced Hypertension (PIH) (p-value=0.0392) were significant. Neonatal shock (p-value=0.001) and Hypoxic- ischaemic Encephalopathy (HIE) (p-value=0.0049) were significant risk factors for AKI in this study. Conclusion: Perinatal asphyxia is one of the common causes of neonatal mortality, with AKI being the earliest and most common complication as seen in the current study, where 61.1% of neonates with perinatal asphyxia had AKI. By early detection and prevention of risk factors causing AKI in perinatal asphyxia, neonatal mortality can be reduced significantly.

The association between pre-eclampsia and neonatal complications in relation to gestational age.

There has been limited research about the associations between pre-eclampsia and neonatal complications in relation to gestational age. This register-based study aimed to address that gap in our knowledge. We used Swedish Medical Birth Register to carry out a population-based study on primiparas with singleton pregnancies from 1999 to 2017. Descriptive statistics and logistic regressions were used to study the associations between pre-eclampsia and neonatal complications in different gestational ages. The data is presented as adjusted odds ratios (aORs) with 95% CI. The study comprised 805 591 primiparas: 2.9% had mild to moderate pre-eclampsia and 1.4% had severe pre-eclampsia. Neonates born to women with pre-eclampsia had increased risks of several complications compared to those born to mothers without pre-eclampsia. After adjustment for confounding variables, the risk of being small for gestational age (aOR 5.3, CI: 5.1-5.5) and needing resuscitation (aOR 2.6, CI: 2.4-2.7) were increased. The risk of a low Apgar score and convulsions/hypoxic ischemic encephalopathy was increased at 32-41 weeks of gestation. Moreover, the overall risk of sepsis (aOR 1.9. CI: 1.8-2.1) and perinatal death (aOR 1.2, CI: 1.1-1.5) was also increased. Compared with infants of mothers without pre-eclampsia, those exposed to pre-eclampsia had higher risks of all the studied neonatal complications.

Clinical and Electrophysiological Evaluation of Neonatal Seizures

Neonatal seizures are the most prevalent and distinctive sign of neurologic dysfunction in early-life. In spite the recent advances in medical care and technology in newborn intensive care units (NICU), it remains an important clinical issue of diagnosis, treatment, and prognosis. This was a retrospective, observational cohort study of neonates with seizures treated in the Ondokuz Mayıs University Faculty of Medicine NICU. Demographics of the babies, risk factors and etiology of seizure, type of clinical seizure, electroencephalographic and radiological findings, and anti-seizure treatments were recorded. The incidence of neonatal seizures was 4.5% in NICU admissions. Seventy-two babies with seizures included, 69,4% were diagnosed with electroclinical seizures. The most common seizure types were clonic (35.8%) and motor automatisms (32.8%). Perinatal asphyxia/hypoxic ischemic encephalopathy (HIE) (29.2%) was the most common etiological factor, whereas hypoglycemia was the most common metabolic problem (15.3%). Eighty-one percent of seizures due to HIE were observed in the first 48 h. Hyperbilirubinemia (kern icterus), hypocalcemia, and idiopathic neonatal convulsions were observed after the first 48 h. Abnormal findings were detected in 76.4% of electroencephalographies obtained during the neonatal period. Phenobarbital was the first-line therapy in 98.6% of babies, and 83.3% of the infants were seizure-free with phenobarbital. Seizures are common in the neonatal period and may be associated with significant brain damage. Seizures appear as an important symptom of the underlying pathology and not as a disease.

Mfat-1 ameliorates cachexia after hypoxic-ischemic brain damage in mice by protecting the hypothalamus-pituitary-adrenal axis

AimsCachexia, a metabolic syndrome, affects 21 % of patients suffering from ischemic encephalopathy. However, the specific mechanism and prevention measures are still unclear. Omega-3 polyunsaturated fatty acids (n−3 PUFAs) have been proven to reduce inflammatory cytokine levels during ischemic events, but whether they have a protective effect against cachexia after hypoxic-ischemic brain damage (HIBD) remains unclear. Main methodsC57BL/6J wild-type and mfat-1 transgenic male mice were treated with and without HIBD. One day after HIBD, the epididymal white fat, gastrocnemius muscle and hypothalamus were weighed and analyzed the phenotypic changes. RNA sequencing was applied to gastrocnemius muscle to identify differential genes and pathways in HIBD groups. The effect of HPA axis on cachexia post-HIBD was examined via adrenalectomy, dexamethasone (0.1 mg/kg), and corticosterone injection (100 mg/kg). Key findingsThe results showed that the incidence of cachexia in mfat-1 mice, which produce high proportion of n−3 PUFAs, was significantly lower than that in wild-type mice post-HIBD. Cachexia-related factors, such as inflammation, muscle atrophy and lipid metabolism were significantly improved in mfat-1 HIBD. RNA sequencing revealed that catabolic and proteasome pathways were significantly downregulated. In hypothalamus, inflammatory cytokines, lipid peroxidation levels were reduced. Corticosterone, glucocorticoid receptor, and dexamethasone suppression test all showed that mfat-1 improved the dysfunction of the HPA axis post-HIBD. The present study elucidated for the first time that mfat-1 reduced HIBD-induced hyperactivation of the HPA axis in mice by reducing inflammation and oxidative stress and contributed to the reduction of metabolic imbalance in peripheral tissues. SignificanceOur study provides mechanistic information for the development of intervention strategies to prevent cachexia.

LINC00938 alleviates hypoxia ischemia encephalopathy induced neonatal brain injury by regulating oxidative stress and inhibiting JNK/p38 MAPK signaling pathway

Hypoxic-ischemic encephalopathy (HIE) is an important factor leading to permanent damage of central nervous system (CNS) and even neonatal death. Long non-coding RNAs (lncRNAs) has been shown to get involved in the pathogenesis of nervous system diseases. LINC00938 is an intergenic lncRNA which is reported to be involved in neurodegenerative disease. However, the potential role of LINC00938 in nerve injury of neonatal HIE is undetermined. Here, we found that the expression of LINC00938 in the whole blood of neonates with HIE was downregulated compared with the non-HIE group. Functional study revealed that the expression of LINC00938 was significantly decreased in oxygen-glucose deprivation (OGD)-induced SH-SY5Y. Knockdown of LINC00938 induced the neural cell apoptosis by increased the protein level of Bax, Cleaved-Caspase3 and decreased the expression of Bcl-2. In addition, overexpression of LINC00938 prevented the apoptosis of SH-SY5Y from OGD injury. RNA-seq analysis showed that MAPK signaling was involved in the anti-apoptosis function of LINC00938. LINC00938 knockdown induced the activation of c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase, and inhibited the activation of ERK signaling. However, LINC00938 play neuroprotective role in OGD-induced SH-SY5Y by suppression the phosphorylation of JNK and p38 MAPK rather than regulation of ERK signaling pathway. Further analyses illustrated that the cell apoptosis of neuronal cell was dependent on the elevation of reactive oxygen species (ROS) and result in mitochondria dysfunction in LINC00938 knockdown SH-SY5Y. Pretreated with ROS inhibitor N-acetylcysteine amide (NACA) dramatically suppressed LINC00938 knockdown induced oxidative stress and mitochondria dysfunction which induced cell apoptosis. In addition, NACA treatment significantly reduced the expression of p-JNK and p-p38 in OGD-induced SH-SY5Y. Furthermore, overexpression of LINC00938 displayed a notably neuroprotective effect by suppress central nervous system cell apoptosis via alleviating oxidative stress in CoCl2-induced hypoxic HIE model of zebrafish. Taken together, these results suggested that LINC00938 can act as a neuroprotective factor to inhibit oxidative stress and apoptosis of CNS under HIE conditions.

Yap1-Usp14 Axis Inhibits Neuronal Mitophagy During Neonatal Hypoxia-Ischemia Encephalopathy by Regulation of Beclin-1 Ubiquitination in Mouse.

Neonatal hypoxic-ischemic encephalopathy (HIE) that results from perinatal cerebral hypoxia-ischemia has become one of the leading causes of acute mortality and chronic disability in infants and children. Despite that neuronal mitophagy and subsequent clearance of damaged neurons exert protective effect, the pathogenesis of HIE and effective treatment strategies for intervention of HIE remain poorly understood. Here, we report that ubiquitin-specific protease 14 (Usp14, a deubiquitinating enzyme) is closely associated with HIE progression by its negative regulation in neuronal mitophagy in mouse. The expression of Usp14 is elevated in both an oxygen-glucose deprivation (OGD) mouse neuronal cell line culture model in vitro and a HIE mouse model in vivo. Mechanistically, OGD treatment activates Hippo signaling that enhances Yap1 phosphorylation levels at Ser-127 but inhibits Yap1 protein level, which potentiates Usp14 transcription and leads to the downregulated ubiquitination at Lys-63 of Beclin-1, a key molecule in autophagy, resulting in the suppressed neuronal mitophagy, subsequent failure in the clearance of damaged neurons, and finally possible dysregulation in brain functions. Thus, our results provide with Usp14 as a novel target and treatment strategy for intervention of HIE, which may help diagnose and treat HIE in clinic.

Stellate ganglion block suppresses hippocampal ferroptosis to attenuate cerebral ischemia-reperfusion injury via the Hippo pathway.

Ischemic stroke is a disabling and fatal disease caused by the insufficient blood supply to the brain. Stellate ganglion block (SGB) is a type of anesthesia commonly used to relieve pain. Here, we sought to identify the effects of SGB on cerebral ischemia-reperfusion (I/R) injury. The middle cerebral artery occlusion (MCAO) model was established in rats. The brain injury was assessed using the 2,3,5-triphenyl-tetrazolium-chloride (TTC) staining assay and neurological score. Ferroptosis was analyzed by detecting cell death, Fe2+ content, glutathione (GSH), malonic dialdehyde (MDA), superoxide dismutase (SOD), and ferroptosis-related factors. The mechanisms of SGB were assessed using the western blot. The results showed that I/R increased brain infarction and damaged neurological function. SGB decreased I/R-induced infarction and improved neurological function. Meantime, SGB inhibited ferroptosis of the hippocampus induced by I/R via the Hippo pathway. and the Yes1 associated transcriptional regulator (YAP) of this pathway was positively correlated with the ferroptosis-related solute carrier family 7 member 11 (SLC7A11). Inhibition of the Hippo pathway reversed the effects of SGB on brain injury and ferroptosis. In conclusion, SGB inhibited ferroptosis of hippocampal neurons via activating the Hippo pathway and thereby alleviated I/R injury. The data provide a novel insight into the treatment of ischemic stroke and even other ischemic encephalopathies.

Overcoming Challenges of Deceased Organ Donation in Indian Private Hospitals.

Overcoming Challenges of Deceased Organ Donation in Indian Private Hospitals.

Serum calcium levels as biomarkers of birth asphyxia in neonates

<p>Background and objective: Birth asphyxia is a common pathological condition seen in newborns with increased morbidity and mortality. Grave consequences following birth asphyxia require earlier recognition of the precipitating factors and prompt treatment in intensive care units. Multiple electrolyte imbalance has been related to this condition. This study aimed at determining the mean serum total calcium levels in neonates with birth asphyxia.</p>
 <p>Methods: This cross sectional study was performed at the neonatal intensive care unit of the Pediatric Department of Fauji Foundation Hospital, Rawalpindi, Pakistan over a period of 6 months. A total of 100 full-term neonates of either gender with evidence of birth asphyxia of any stage were enrolled on their first hour of birth. Serum calcium levels were estimated in each neonate at 24 hours after birth.</p>
 <p>Results: A total of 60 (60%) neonates were males. Mean serum calcium levels were found to be 7.64 mg/dl ± 0.59 with no significant difference among males and females (7.67 ± 0.64 and 7.59 ± 0.50 mg/dl, respectively). Neonatal distribution in Stages I, II, and III was 64 (64.0%), 23 (23.0%), and 13 (13.0%), respectively. Hypoxic-ischemic encephalopathy stage stratification with mean serum calcium levels with higher stages deciphered significant correlation (7.89 ± 0.54, 7.36 ± 0.28, and 6.88 ± 0.28 mg/dl, respectively, in stage I, II, and III).</p>
 <p>Conclusion: Markedly decreased levels of mean serum calcium were seen in higher hypoxic stages with ischemic encephalopathy hence delineating a linear correlation with the onset and progression of disease.</p>

Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia-Ischemia Encephalopathy: An In Vitro Study.

Hypoxia-ischemia encephalopathy results from the interruption of oxygen delivery and blood flow to the brain. In the developing brain, it can lead to a brain injury, which is associated with high mortality rates and comorbidities. The hippocampus is one of the brain regions that may be affected by hypoxia-ischemia with consequences on cognition. Unfortunately, clinically approved therapeutics are still scarce and limited. Therefore, in this study, we aimed to test three repurposed drugs with good pharmacological properties to evaluate if they can revert, or at least attenuate, the deleterious effects of hypoxia-ischemia in an in vitro model. Edaravone, perampanel, and metformin are used for the treatment of stroke and amyotrophic lateral sclerosis, some forms of epileptic status, and diabetes type 2, respectively. Through cell viability assays, morphology analysis, and detection of reactive oxygen species (ROS) production, in two different cell lines (HT-22 and SH-SY5Y), we found that edaravone and low concentrations of perampanel are able to attenuate cell damage induced by hypoxia and oxygen-glucose deprivation. Metformin did not attenuate hypoxic-induced events, at least in the initial phase. Among these repurposed drugs, edaravone emerged as the most efficient in the attenuation of events induced by hypoxia-ischemia, and the safest, since it did not exhibit significant cytotoxicity, even in high concentrations, and induced a decrease in ROS. Our results also reinforce the view that ROS and overexcitation play an important role in the pathophysiology of hypoxia-ischemia brain injury.

Preeclampsia

(N Engl J Med. 2022;386:1817–1832. doi: 10.1056/NEJMra2109523) Preeclampsia affects 2% to 4% of global pregnancies, targeting low- and middle-income countries specifically, and it results in serious complications for 5% to 20% of women. Preeclampsia often causes or contributes to endothelial damage, increased peripheral vascular resistance, hypertension, pulmonary edema, hemorrhagic stroke, ischemic encephalopathy, kidney, liver, hematologic, and perinatal injury. Demographic characteristics, medical history, current pregnancy characteristics, physiological abnormalities, abnormal laboratory test results, and ultrasonography abnormalities are risk factors for preeclampsia. These risk factors play a critical role in early identification and treatment during pregnancy.

Design, synthesis and neurite outgrowth activity of novel ganglioside GM1 derivatives by remodeling of the fatty acid moiety

Ganglioside GM1 is a glycosphingolipid found on mammalian cell membranes, and it is involved in ischemic encephalopathy, spinal cord injury and neurodegenerative diseases. Fatty acids, as a structure module of GM1, have been reported to affect its physiological function and neurite growth activity. Due to the limitation of preparation methods, the function of GM1 derivatives containing different fatty acids in nerve cells has not been systematically studied. To discover novel GM1 derivatives as nerve growth-promoting agents, we developed an efficient SA_SCDase enzymatic synthetic system of GM1 derivatives, yielding twenty GM1 derivatives with unsaturated fatty acid chains in high total yields (16–67%). Subsequently, the neurite outgrowth activities of GM1 derivatives were assessed on Neuro2a Cells. Among all the GM1 derivatives, GM1 (d18:1/C16:1) induced demonstrably neurite outgrowth activity. The subsequent RNA-sequencing (RNA-seq) and Western blot analysis was then performed and indicated that the mechanism of nerve cells growth involved cholesterol biosynthesis regulation by up-regulating SREBP2 expression or ERBB4 phosphorylation to activate the PI3K-mTOR pathway.

EVALUATION OF VARIOUS CAUSES OF CEREBRAL VISUAL IMPAIRMENT IN CHILDREN AT TERTIARY CARE CENTRE

Purpose: The purpose of this study is to evaluate the etiology, associated ophthalmological and neurological ndings of cerebral visual impairment (CVI) in children at a tertiary care center. Methods: A retrospective study was conducted on 71 patients visiting between February 2020 to August 2021 at a tertiary care hospital, J.L.N. medical college and hospital, Ajmer, Rajasthan. Diagnosis of CVI was based on ocular examination found poor visual function that could not be accounted by age, ocular ndings and neuroimaging.Results: The records of 44 boys and 27 girls were analysed. Majority of them were <3yrs (40.8%) . The most common etiology was perinatal hypoxia (29%), followed by prematurity (22.5%). Moreover, 9(12.7%) showed mixed aetiology, 8(11.3%) had hydrocephalus and 7(9.9%) had hypoglycemia . Amongst the ocular associations, refractive error was the most common, seen in 32 (45%) children, while strabismus in 31 (44%), nystagmus in 22(31%). Thirty two (45%) children had associated developmental delay, while 38(53%) had seizures. The most common ndings were ischemic encephalopathy (31%), periventricular leukomalacia (23%), cortical and subcortical atrophy and structural malformations (24%). Conclusion: CVI is of increasing importance as a cause of vision impairment in children. The major causes for CVI tend to be perinatal hypoxia followed by prematurity. Establishing the etiology for these children at early age may aid in early rehabilitation of these children.

Routine Tracheal Intubation and Meconium Suctioning in Non-Vigorous Neonates with Meconium-Stained Amniotic Fluid: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis is the comparison of endotracheal intubation and suctioning to immediate resuscitation without intubation of non-vigorous infants > 34 weeks’ gestation delivered through meconium-stained amniotic fluid (MSAF). Randomized, non-randomized clinical trials and observational studies were included. Data sources were PubMed/Medline and Cochrane Central Registry of Controlled Trials, from 2012 to 2021. Inclusion criteria were non-vigorous infants born through MSAF with gestational age > 34 weeks and sample size ≥ 5. We calculated overall relative risks (RR) and mean differences (MD) with a 95% confidence interval (CI) to determine the impact of endotracheal suction (ETS) in non-vigorous infants born through MSAF. The outcomes presented are the incidence of neonatal mortality, meconium aspiration syndrome (MAS), transient tachypnea, need for positive pressure ventilation, respiratory support, persistent pulmonary hypertension treatment, neonatal infection, ischemic encephalopathy, admission to neonatal intensive care unit (NICU) and the duration of hospitalization between ETS and non-ETS group. Six studies with a total sample of 1026 patients fulfilled the inclusion criteria. Statistically non-significant difference was observed in RR between two groups with regards to mortality (1.22, 95% CI 0.73–2.04), occurrence of MAS (1.08, 95% CI 0.76–1.53) and other outcomes, and MD in hospitalization duration. There is no sufficient evidence to suggest initiating endotracheal suction soon after birth in non-vigorous meconium-stained infants as routine.

Homer1 promotes the conversion of A1 astrocytes to A2 astrocytes and improves the recovery of transgenic mice after intracerebral hemorrhage

BackgroundInflammation induced by intracerebral hemorrhage (ICH) is one of the main causes of the high mortality and poor prognosis of patients with ICH. A1 astrocytes are closely associated with neuroinflammation and neurotoxicity, whereas A2 astrocytes are neuroprotective. Homer scaffolding protein 1 (Homer1) plays a protective role in ischemic encephalopathy and neurodegenerative diseases. However, the role of Homer1 in ICH-induced inflammation and the effect of Homer1 on the phenotypic conversion of astrocytes remain unknown.MethodsFemoral artery autologous blood from C57BL/6 mice was used to create an ICH model. We use the A1 phenotype marker C3 and A2 phenotype marker S100A10 to detect astrocyte conversion after ICH. Homer1 overexpression/knock-down mice were constructed by adeno-associated virus (AAV) infection to explore the role of Homer1 and its mechanism of action after ICH. Finally, Homer1 protein and selumetinib were injected into in situ hemorrhage sites in the brains of Homer1flox/flox/Nestin-Cre+/− mice to study the efficacy of Homer1 in the treatment of ICH by using a mouse cytokine array to explore the potential mechanism.ResultsThe expression of Homer1 peaked on the third day after ICH and colocalized with astrocytes. Homer1 promotes A1 phenotypic conversion in astrocytes in vivo and in vitro. Overexpression of Homer1 inhibits the activation of MAPK signaling, whereas Homer1 knock-down increases the expression of pathway-related proteins. The Homer1 protein and selumetinib, a non-ATP competitive MEK1/2 inhibitor, improved the outcome in ICH in Homer1flox/flox/Nestin-Cre+/− mice. The efficacy of Homer1 in the treatment of ICH is associated with reduced expression of the inflammatory factor TNFSF10 and increased expression of the anti-inflammatory factors activin A, persephin, and TWEAK.ConclusionsHomer1 plays an important role in inhibiting inflammation after ICH by suppressing the A1 phenotype conversion in astrocytes. In situ injection of Homer1 protein may be a novel and effective method for the treatment of inflammation after ICH.

Identification, diagnosis, and early intervention of children with developmental language disorder in Ningxia.

BackgroundIt is reported that the incidence of language development disorder in children at the age of 2 is as high as 17.0%. Timely discovery of the high-risk factors of language development disorder in children and early intervention can greatly reduce the incidence of language development disorder and shorten the course and condition of the patients with language development disorder. Therefore, in order to facilitate prompt diagnosis and early interventions for children with language development disorder (DLD) and improve their language ability, this study explored the influence of perinatal factors on the language development of children in Ningxia and identified the unfavorable and favorable factors that influenced language development.MethodsChildren diagnosed in the General Hospital of Ningxia Medical University during 2018–2021 who met the screening criteria for DLD and practical pediatric diagnostic criteria for DLD were enrolled in this study. Perinatal factors (gestational age, weight, sex, delivery mode, maternal age, presence of intrauterine infection, asphyxia) were retrospectively analyzed. The perinatal factors affecting language development were assessed using a one-way analysis of variance (ANOVA).ResultsAmong 1,500 children aged 0–3, 240 cases (16.00%) had language delay. Of these, 122 were male and 118 were female. There were 115 cases of comprehension and expression disorder, 30 cases of articulation disorder, and 90 cases of mixed manifestation. And there were 194 cases with definite intrauterine and perinatal high-risk factors or neonatal diseases, accounting for 80.83% of the total number of children with language delay.ConclusionsIn Ningxia, factors in the neonatal period are the main cause of DLD, followed by fetal and maternal factors. Ischemic encephalopathy is the most common factor.