Early Morbidities of Hypoxia-Ischemic Encephalopathy in Term Neonates With a Resistive Index as a Prognostic Indicator.

Background Acidosis, hypoxemia, and hypercarbia are symptoms of a syndrome known as perinatal asphyxia that occurs during the first and second stages of labor and shortly after delivery due to poor gas exchange. The Doppler technique is a non-invasive way to assess the risk of neurodevelopment damage in hypoxic-ischemic encephalopathy (HIE) that may be done at the patient's bedside without disturbing them. The study aims to evaluate cranial ultrasound findings in HIE and investigate the role of resistive index (RI) values assessed by color Doppler transcranial ultrasonography in predicting early morbidities in neonates with HIE within 72 hours of life. Methodology Prospective observational research was carried out at the north Karnataka region's tertiary newborn critical care unit. The study included 54 infants with HIE in total. The male-to-female ratio was 1.7:1, with 34 (63%) male and 20 (37%) female newborns. Results About 32 instances had grade I HIE, 8 had grade II HIE, and 14 had grade III HIE. In 35 instances (64.81%), the RI was normal; in 19 cases (35.19%), it was abnormal. Increased periventricular density and cerebral parenchyma echo density were common Doppler ultrasonography findings. Roughly 93% of people survived, and 7% of people died from HIE. Seizures (12.96%) and acute renal damage (33.33%) were the most frequent consequences. Conclusion In instances of HIE, the RI was revealed to be a favorable predictive indicator for newborn prognosis. Counseling and educating parents about early morbidities, anticipated long-term consequences, and the need for follow-up will all benefit from it. Additionally, color Doppler is a practical and secure diagnostic method for determining a newborn's level of HIE.

Direct Multi-Deuterium Labelling of Pirtobrutinib.

Herein, we demonstrate an efficient method for multi-deuterium labelling of pirtobrutinib-a Bruton's tyrosine kinase inhibitor recently approved by the FDA-using a straightforward hydrogen isotope exchange (HIE) reaction. A remarkably high level of deuterium incorporation was achieved using an excess of a Kerr-type iridium catalyst. The key factor in the significant deuterium labelling was the decision to employ a deuterium uniformly labelled solvent, chlorobenzene-d5, at an elevated temperature. Virtually, no d0-d3 species were detected, with only traces of d4-d5 isotopomers (< 5%) observable in the mass spectrum of pirtobrutinib-d8, fulfilling requirements for stable isotope-labelled internal standard. The labelled compound-mainly consisting of isotopomers d6-d9 at 82.4% of the total abundance-was isolated in a high yield (73%) and purity (99%). Noteworthy, fluorine group acting as a directing group was observed for the first time. Significant incorporation of deuterium in ortho-positions, exceeding 87%, was observed. Interestingly, chlorinated solvent used in the HIE reactions was non-specifically deuterated yielding up to 0.42 deuterium per chlorobenzene molecule even at an exceptionally low iridium catalyst loading of 4.17 × 10-2 mol%.

Hypoxic-Ischemic Encephalopathy: Pathogenesis and Promising Therapies.

Hypoxic-ischemic encephalopathy (HIE) is a brain lesion caused by inadequate blood supply and oxygen deprivation, often occurring in neonates. It has emerged as a grave complication of neonatal asphyxia, leading to chronic neurological damage. Nevertheless, the precise pathophysiological mechanisms underlying HIE are not entirely understood. This paper aims to comprehensively elucidate the contributions of hypoxia-ischemia, reperfusion injury, inflammation, oxidative stress, mitochondrial dysfunction, excitotoxicity, ferroptosis, endoplasmic reticulum stress, and apoptosis to the onset and progression of HIE. Currently, hypothermia therapy stands as the sole standard treatment for neonatal HIE, albeit providing only partial neuroprotection. Drug therapy and stem cell therapy have been explored in the treatment of HIE, exhibiting certain neuroprotective effects. Employing drug therapy or stem cell therapy as adjunctive treatments to hypothermia therapy holds great significance. This article presents a systematic review of the pathogenesis and treatment strategies of HIE, with the goal of enhancing the effect of treatment and improving the quality of life for HIE patients.

Echinatin alleviates inflammation and pyroptosis in hypoxic-ischemic brain damage by inhibiting TLR4/ NF-κB pathway.

Hypoxic ischemic encephalopathy (HIE) is a primary cause of neonatal death and disabilities. The pathogenetic process of HIE is closely associated with neuroinflammation. Therefore, targeting and suppressing inflammatory pathways presents a promising therapeutic strategy for the treatment of HIE. Echinatin is an active component of glycyrrhiza, with anti-inflammatory and anti-oxidative properties. It is commonly combined with other traditional Chinese herbs to exert heat-clearing and detoxifying effects. This study aimed to investigate the anti-inflammatory and neuroprotective effects of Echinatin in neonatal rats with hypoxic-ischemic brain damage, as well as in PC12 cells exposed to oxygen-glucose deprivation (OGD). In vivo, Echinatin effectively reduced cerebral edema and infarct volume, protected brain tissue morphology, improved long-term behavioral functions, and inhibited microglia activation. These effects were accompanied by the downregulation of inflammatory factors and pyroptosis markers. The RNA sequencing analysis revealed an enrichment of inflammatory genes in rats with hypoxic-ischemic brain damage, and Protein-protein interaction (PPI) network analysis identified TLR4, MyD88, and NF-κB as the key regulators. In vitro, Echinatin reduced the levels of TLR4 relevant proteins, inhibited nuclear translocation of NF-κB, reduced the expression of downstreams inflammatory cytokines and pyroptosis proteins, and prevented cell membrane destructions. These findings demonstrated that Echinatin could inhibit the TLR4/NF-κB pathway, thereby alleviating neuroinflammation and pyroptosis. This suggests that Echinatin could be a potential candidate for the treatment of HIE.

Nuclear Factor Erythroid 2-Related Factor 2 as a Potential Therapeutic Target in Neonatal Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a prominent cause of neonatal mortality and neurodevelopmental disorders; however, effective therapeutic interventions remain limited. During neonatal hypoxic-ischemic injury events, increased reactive oxygen species (ROS) production and decreased antioxidant levels lead to the induction of oxidative stress, which plays a pivotal role in the pathological process of neonatal HIE. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key endogenous antioxidant transcription factor that protects against oxidative stress by promoting the transcription of various antioxidant genes. It has been demonstrated that Nrf2 signaling pathway activation by different compounds may protect against neonatal HIE. This review outlines the role of oxidative stress in neonatal HIE and summarizes the impact of antioxidants on neonatal HIE via activation of the Nrf2 signaling pathway. In conclusion, Nrf2 signaling pathway potentially exerts antioxidant, anti-inflammatory, antiapoptotic and antiferroptotic effects, thereby emerging as a focal point for future neonatal HIE treatment strategies.

Survival, but not the severity of hypoxic-ischemic encephalopathy, is associated with higher mean arterial blood pressure after cardiac arrest: a retrospective cohort study.

Background: This study investigates the association between the mean arterial blood pressure (MAP), vasopressor requirement, and severity of hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). Methods: Between 2008 and 2017, we retrospectively analyzed the MAP 200 h after CA and quantified the vasopressor requirements using the cumulative vasopressor index (CVI). Through a postmortem brain autopsy in non-survivors, the severity of the HIE was histopathologically dichotomized into no/mild and severe HIE. In survivors, we dichotomized the severity of HIE into no/mild cerebral performance category (CPC) 1 and severe HIE (CPC 4). We investigated the regain of consciousness, causes of death, and 5-day survival as hemodynamic confounders. Results: Among the 350 non-survivors, 117 had histopathologically severe HIE while 233 had no/mild HIE, without differences observed in the MAP (73.1 vs. 72.0 mmHg, pgroup = 0.639). Compared to the non-survivors, 211 patients with CPC 1 and 57 patients with CPC 4 had higher MAP values that showed significant, but clinically non-relevant, MAP differences (81.2 vs. 82.3 mmHg, pgroup < 0.001). The no/mild HIE non-survivors (n = 54), who regained consciousness before death, had higher MAP values compared to those with no/mild HIE (n = 179), who remained persistently comatose (74.7 vs. 69.3 mmHg, pgroup < 0.001). The no/mild HIE non-survivors, who regained consciousness, required fewer vasopressors (CVI 2.1 vs. 3.6, pgroup < 0.001). Independent of the severity of HIE, the survivors were weaned faster from vasopressors (CVI 1.0). Conclusions: Although a higher MAP was associated with survival in CA patients treated with a vasopressor-supported MAP target above 65 mmHg, the severity of HIE was not. Awakening from coma was associated with less vasopressor requirements. Our results provide no evidence for a MAP target above the current guideline recommendations that can decrease the severity of HIE.

Glucose instability and outcomes of neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia.

BACKGROUND: To investigate the prevalence and associated outcomes of glucose abnormalities in infants with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). METHODS: Glucose values were reviewed in all HIE infants. Pearson's correlation was used to assess the association of hypo- and hyperglycemic episodes with neonatal brain MRI and neurodevelopmental outcomes (NDO) at 12 & 24 months. RESULTS: Of 153 infants included, 31, 56 and 43 had episodes of hypo-, hyperglycemia and combined, respectively. Hyperglycemia and combined hypo/hyper had higher mortality (p = 0.035), seizures (p = 0.009), and longer hospitalization (p = 0.023). Hypo- and hyperglycemia were associated with parenchymal hemorrhages (p = 0.028 & p = 0.027, respectively). Hypoglycemia was associated with restricted diffusion (p = 0.014), while hyperglycemia was associated with cortical injuries (p = 0.045). Each hour of hyper- or hypoglycemia was associated with 5.2-5.8 times unfavorable outcomes (p < 0.001). CONCLUSION: Blood glucose aberrations were detrimental in HIE infants treated with TH. Optimizing glucose management is crucial in this setting.

Clinical exome sequencing uncovers genetic disorders in neonates with suspected hypoxic-ischemic encephalopathy: A retrospective analysis.

Hypoxic-ischemic encephalopathy (HIE) occurs in up to 7 out of 1000 births and accounts for almost a quarter of neonatal deaths worldwide. Despite the name, many newborns with HIE have little evidence of perinatal hypoxia. We hypothesized that some infants with HIE have genetic disorders that resemble encephalopathy. We reviewed genetic results for newborns with HIE undergoing exome or genome sequencing at a clinical laboratory (2014-2022). Neonates were included if they had a diagnosis of HIE and were delivered ≥35 weeks. Neonates were excluded for cardiopulmonary pathology resulting in hypoxemia or if neuroimaging suggested postnatal hypoxic-ischemic injury. Of 24 patients meeting inclusion criteria, six (25%) were diagnosed with a genetic condition. Four neonates had variants at loci linked to conditions with phenotypic features resembling HIE, including KIF1A, GBE1, ACTA1, and a 15q13.3 deletion. Two additional neonates had variants in genes not previously associated with encephalopathy, including DUOX2 and PTPN11. Of the six neonates with a molecular diagnosis, two had isolated HIE without apparent comorbidities to suggest a genetic disorder. Genetic diagnoses were identified among neonates with and without sentinel labor events, abnormal umbilical cord gasses, and low Apgar scores. These results suggest that genetic evaluation is clinically relevant for patients with perinatal HIE.

MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study.

Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE.

Assessment of the broad-spectrum host targeting antiviral efficacy of halofuginone hydrobromide in human airway, intestinal and brain organotypic models.

Halofuginone hydrobromide has shown potent antiviral efficacy against a variety of viruses such as SARS-CoV-2, dengue, or chikungunya virus, and has, therefore, been hypothesized to have broad-spectrum antiviral activity. In this paper, we tested this broad-spectrum antiviral activity of Halofuginone hydrobomide against viruses from different families (Picornaviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, and Flaviviridae). To this end, we used relevant human models of the airway and intestinal epithelium and regionalized neural organoids. Halofuginone hydrobomide showed antiviral activity against SARS-CoV-2 in the airway epithelium with no toxicity at equivalent concentrations used in human clinical trials but not against any of the other tested viruses.

Distinctive Clinico-electrographic and Radiological Profile of Childhood and Adolescent Seizures.

AIM: Electroencephalogram (EEG) is specific, but not sensitive, for the diagnosis of epilepsy. This study aimed to correlate the clinico-electrographic and radiological features of seizure disorders in children attending a tertiary care centre in northern India. METHODS: Children aged between one to 18 years with seizure episodes were included. Clinical details, including historical as well as physical findings, were evaluated along with EEG and neuroimaging (Magnetic resonance imaging). Details were noted on pre-designed proforma. Variables were analysed by using appropriate statistical methods. RESULTS: A total of 110 children with seizures were enrolled in the study. Male to female ratio was 1.6: 1, and the mean age of the study children was 8 years. The majority of the children were symptomatic for more than one year. The most common seizure type was Generalised Tonic Clonic Seizure (GTCS), and Hypoxic-ischemic Encephalopathy (HIE) sequelae was the most commonly attributed etiology, followed by neurocysticercosis. EEG and neuroimaging findings were found to correlate well with seizure semiology from history. The incidence of febrile seizures was 10% in this study, with nearly three-fourths of them being simple febrile seizures. CONCLUSION: Microcephaly and developmental delay were the most distinctive clinical correlates in children with seizures. There was a fair agreement between the types of seizures described in history and depicted on EEG with Cohen's kappa of 0.4. Also, there was a significant association between the type of seizures on EEG and the duration of symptoms.

Long-Term Neurocognitive Outcomes in Pediatric Nonfatal Drowning: Results of a Family Caregiver Survey.

BACKGROUND: Drowning is a leading cause of brain injury in children. Long-term outcome data for drowning survivors are sparse. This study reports neurocognitive outcomes for 154 children hospitalized following drowning. METHODS: A survey for parent caregivers was distributed online. Likert scale items assessed 10 outcome variables in four domains: motor (three), perception (three), language (three), and social/emotional (one). Cluster analysis, outcome relative risk, and descriptive statistics were applied. RESULTS: Of 208 surveys received, 154 met inclusion criteria. Coma was the most common admission status (n = 137). Cluster analysis identified three outcome groups: Mild (n = 39), Moderate (n = 75), and Severe (n = 40). Motor impairment with cognitive and perceptual sparing (deefferentation) was present in Moderate (P < 1 × 10-26) and Severe (P < 1 × 10-12) but absent in Mild. Locked-in state was endorsed in both Moderate (83%) and Severe (70%). The strongest predictor of good outcome (Mild) was hospitalization with no medical intervention (relative risk [RR] = 6.7). Responsivity on admission (RR = 4.2) or discharge (RR = 12.22) also predicted good outcome. In-hospital prognostication and counseling predicted outcome weakly (RR = 1.3) or not at all. CONCLUSIONS: Long-term outcomes in pediatric drowning ranged widely. Overall, motor impairments exceeded perceptual or cognitive (P < 1 × 10-18), with "locked-in state" endorsed in most (93 of 154). The strongest predictors of good outcome were the lack of necessity for interventions and responsivity on admission or discharge. The eponym "Conrad syndrome" is proposed for locked-in state following nonfatal drowning in children.

Acute kidney injury in infants with hypoxic-ischemic encephalopathy.

BACKGROUND: This study aimed to investigate the prevalence of acute kidney injury (AKI) in infants with varying degrees of hypoxic-ischemic encephalopathy (HIE) and its associated outcomes, including mortality and length of stay (LOS). METHODS: The study used the National Inpatient Sample (NIS) dataset from 2010 to 2018. Regression analysis was used to control confounding variables. RESULTS: Of 31,220,784 infants included in the study, 30,130 (0.1%) had HIE. The prevalence of AKI was significantly higher in infants with HIE (9.0%) compared to those without (0.04%), with an adjusted odds ratio (aOR) of 77.6 (CI:70.1-85.7, p < 0.001), with the highest prevalence of AKI in infants with severe HIE (19.7%), aOR:130 (CI: 107-159), p < 0.001). Infants with AKI had a higher mortality rate compared to those without AKI in those diagnosed with any degree of HIE (28.9% vs. 8.8%), aOR 3.5 (CI: 3.2-3.9, p < 0.001), particularly among those with severe HIE, aOR:1.4 (1.2-1.6, p < 0.001). CONCLUSIONS: HIE is associated with an increased prevalence of AKI. Infants with severe HIE had the highest prevalence of AKI and associated mortality. The study highlights the need for close monitoring and early detection of AKI in infants with HIE, particularly those with severe HIE, to ameliorate the associated adverse outcomes.

Hypoxic Ischemic Encephalopathy with Cervical Spinal Cord Injury: A Diagnostic Dilemma.

Perinatal spinal cord injury is a relatively uncommon, but a frequently misdiagnosed disorder. Improvements in obstetric care have certainly led to a decrease in the incidence of birth related spinal cord trauma but unfortunately the incidence of hypoxic-ischemic encephalopathy is still very high. The exact incidence of spinal cord trauma is difficult to determine because the spinal cord is not routinely examined in far and few neonatal autopsies done in India. Here, authors present a neonate who received treatment for birth asphyxia and then had extubation failure which made the clock tick towards cervical cord injury. This baby had a hemorrhagic contusion of cervical spinal cord.

A New Approach for Exploring Reperfusion Brain Damage in Hypoxic Ischemic Encephalopathy.

Reperfusion is an essential pathological stage in hypoxic ischemic encephalopathy (HIE). Although the Rice-Vannucci model is widely used in HIE research, it remains difficult to replicate HIE-related reperfusion brain injury. The purpose of this study is to establish a rat model of hypoxia ischemia reperfusion brain damage (HIRBD) using a common carotid artery (CCA) muscle bridge in order to investigate the mechanisms of cerebral resistance to hypoxic-ischemic and reperfusion brain damage. Random assignment of Sprague-Dawley (SD) rats to the Sham, HIRBD, and Rice-Vannucci groups. Changes in body weight, mortality rate, spontaneous alternation behavior test (SAB test), and dynamic changes in cerebral blood flow (CBF) were detected. The damaged cerebral cortices were extracted for morphological comparison, transcriptomic analysis, and quantitative real-time PCR. Harvesting the hippocampus for transmission electron microscopy (TEM) detection. As a result, CCA muscle bridge could effectively block CBF, which recovered after the muscle bridge detachment. Pathological comparison, the SAB test, and TEM analysis revealed that brain damage in Rice-Vannucci was more severe than HIRBD. Gpx1, S100a6, Cldn5, Esr1, and Gfap were highly expressed in both HIRBD and Rice-Vannucci. In conclusion, the CCA muscle bridge-established HIRBD model could be used as an innovative and dependable model to simulate pathological process of HIRBD.

A novel clinical risk scoring system for neurodevelopmental outcomes among survivors of neonatal hypoxic-ischemic encephalopathy (HIE).

OBJECTIVE: We aimed to develop a risk scoring system as a predictor of 24-month neurodevelopmental outcomes (cognitive, language, and motor) for neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). METHODS: This was a chart review of infants with HIE treated with therapeutic hypothermia who were admitted to the Neonatal Intensive Care Unit (NICU) at the University of Michigan between 2009 and 2019 and followed in the neonatal developmental clinic until 24 months of age. We examined bivariate associations between the neonatal characteristics and Bayley-III scores. We then performed stepwise logistic regression. To create the risk scores, a participant was given one point for each of the factors included in the final model. RESULTS: Fifty-five infants were included. The final model for Bayley cognitive abnormality included abnormal neonatal neurologic exam (p < 0.0001), white matter/watershed MRI abnormality (p = 0.01), 5-min Apgar score (p = 0.02), and EEG-confirmed seizures (p = 0.04). The model for language abnormality included abnormal neurologic exam (p = 0.0002), seizures (p = 0.007), clinical severity of HIE (p = 0.06), and basal ganglia/thalamus MRI abnormality (p = 0.17). The model for motor abnormality included seizures (p = 0.03), abnormal neurologic exam (p = 0.06) and basal ganglia/thalamus MRI abnormality (p = 0.02). The positive predictive values for the risk scores were 60 %, 85 % and 71 %, respectively, for the Bayley-III cognitive, language and motor domains. CONCLUSION: Our study identifies early clinical features that differentially predict domains of neurodevelopmental outcome and associated risk scores that may be of value to both clinicians and families. This novel scoring system should next be validated in a larger, prospective study.

Electroencephalography Prediction of Neurological Outcomes After Hypoxic-Ischemic Brain Injury: A Systematic Review and Meta-Analysis.

Background. Predicting neurological outcomes after hypoxic-ischemic brain injury (HIBI) is difficult. Objective. Electroencephalography (EEG) can identify acute and subacute brain abnormalities after hypoxic brain injury and predict HIBI recovery. We examined EEG's ability to predict neurologic outcomes following HIBI. Method. A PRISMA-compliant search was conducted in the Medline, Embase, Cochrane, and Central databases until January 2023. EEG-predicted neurological outcomes in HIBI patients were selected from relevant perspective and retrospective cohort studies. RevMan did meta-analysis, while QDAS2 assessed research quality. Results. Eleven studies with 3761 HIBI patients met the inclusion and exclusion criteria. We aggregated study-level estimates of sensitivity and specificity for EEG patterns determined a priori using random effect bivariate and univariate meta-analysis when appropriate. Positive indicators and anatomical area heterogeneity impacted prognosis accuracy. Funnel plots analyzed publication bias. Significant heterogeneity of greater than 80% was among the included studies with P < 0.001. The area under the curve was 0.94, the threshold effect was P < 0.001, and the sensitivity and specificity, with 95% confidence intervals, were 0.91 (0.84-0.99) and 0.86 (0.75-0.97). EEG detects status epilepticus and burst suppression with good sensitivity, specificity, and little probability of false-negative impairment result attribution. Study quality varied by domain, but patient flow and timing were well conducted in all. Conclusion. EEG can predict the outcome of HIBI with good prognostic accuracy, but more standardized cross-study protocols and descriptions of EEG patterns are needed to better evaluate its prognostic use for patients with HIBI.

The Role of Cystathionine-ß-Synthase, H2S, and miRNA-377 in Hypoxic-Ischemic Encephalopathy: Insights from Human and Animal Studies.

We aimed to investigate the mechanism underlying the roles of miRNA-377, Cystathionine-ß-synthase (CBS), and hydrogen sulfide (H2S) in the development of hypoxic-ischemic encephalopathy (HIE). We investigated the relationship between CBS, H2S, and miR-377 in both humans with HIE and animals with hypoxic-ischemic insult. An animal model of fetal rats with hypoxic-ischemic brain injury was established, and the fetal rats were randomly assigned to control and hypoxic-ischemic groups for 15 min (mild) and 30 min (moderate) groups. Human samples were collected from children diagnosed with HIE. Healthy or non-neurological disease children were selected as the control group. Hematoxylin-eosin (HE) staining, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot were used to conduct this study. Hypoxia-ischemia induced pathological alterations in brain tissue changes were more severe in groups with severe hypoxic insult. miRNA-377 expression levels were upregulated in brain tissue and serum of fetal rats and human samples with HIE compared to controls. Conversely, CBS and H2S expression levels were significantly decreased in both human and animal samples compared to controls. Our findings suggest that CBS is a target gene of miR-377 which may contribute to the development of HIE by regulating CBS/H2S. H2S has a protective effect against hypoxic damage in brain tissue. The study provides new insights into the potential mechanisms underlying the protective role of H2S in hypoxic brain damage and may contribute to the development of novel therapies for HIE.

Crisis neonatales: evaluacion, diagnostico y tratamiento / Neonatal seizures: evaluation, diagnosis, and treatment

Resumen Las crisis convulsivas tienen una alta incidencia en la etapa neonatal, representando la principal manifes tación de disfunción neurológica. Ciertas condiciones fisiológicas del cerebro neonatal facilitan su aparición. Su diagnóstico puede ser un reto debido a que su semio logía no es tan clara comparado con niños mayores, y además, es necesario la confirmación por medio de EEG continuo o aEEG. Su reconocimiento oportuno es muy importante para un adecuado tratamiento y así evitar un impacto negative en el pronóstico a largo plazo. En la siguiente revisión, recapitulamos la fisiopatología, las causas y la clasificación de las crisis convulsivas neo natales, además de su correcto abordaje y las mejores opciones terapéuticas para su tratamiento dependiendo de la causa.

Abstract Seizures have a high incidence in the neonatal stage, being the main manifestation of neurological dysfunc tion. Certain physiological conditions of the neonatal brain facilitate its appearance. Its diagnosis can be a challenging because its semiology is not as clear as in older children, furthermore, confirmation by either EEG or aEEG is necessary. Its timely recognition is very im portant for adequate treatment and thus avoid a nega tive impact on the long-term outcome. In the following review, we recapitulate the pathophysiology, causes, and classification of neonatal seizures, as well as their correct approach and the best therapeutic options for their treatment depending on the cause.