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Timely diagnosis of cerebral disorders both in the prenatal period and in the early neonatal period, as well as early rehabilitation treatment is the basis for the prevention of childhood disability. To this end, the so-called Early Intervention System is being introduced in Ukraine. The effectiveness of early intervention techniques directly depends on timely diagnosis and correctly chosen intervention tactics. Given the high neuroplasticity of the developing brain, it is advisable to start the elements of neurodevelopmental therapy from infancy. The aim of the work is to evaluate the effectiveness of methods of early intervention in children of the first 3 months of life who have suffered hypoxic-ischemic CNS damage in the neonatal period, by assessing the main indicators of psycho-motor development. 101 children who were treated in the neonatal pathology department due to hypoxic-ischemic CNS damage and did not have concomitant somatic pathology were examined. The children were in the ward for rehabilitation. To assess the effectiveness of comprehensive rehabilitation in young children, it is advisable to use adapted for Ukraine scale of Munich functional developmental diagnostics, which allows to assess the child's development in all major areas, its harmony and effectiveness of rehabilitation measures during the first 3 years of life. Statistical processing of the obtained results should be performed in the license package "Statistica 6.1 for Windows". Timely diagnosis of cerebral disorders both in the prenatal period and in the early neonatal period, as well as early rehabilitation treatment is the basis for the prevention of childhood disability. Given the high neuroplasticity of the developing brain, it is advisable to start the elements of neurodevelopmental therapy from infancy. The effectiveness of the methods recommended for use depends on timely diagnosis and correctly chosen intervention tactics. Assessment of the effectiveness of care for children at risk of deviant psychomotor development should be based on the application of the criteria and scales recommended by international expert groups, which are adapted in our country. Signs of full-fledged early intervention in the region are: perinatal diagnosis of congenital pathology, timely provision of medical and rehabilitation, social and special pedagogical services to children aged 0 to 3 years and their families. In order to achieve the set goals, in our opinion, the priority measures should be steps to implement the national protocol for care for children with perinatal CNS injuries, approval and implementation in Ukraine of the modern International Classification of Functioning, Life and Health Restrictions, providing medical care, rehabilitation and social services for young children.

To study the features of enzymatic and metabolic support of oxidative homeostasis in patients with hypoxic-ischemic brain lesions before and after cardiac surgery using artificial circulation we examined 38 patients, in particular: ischemic stroke — 14 people, encephalopathy — 15 people, severe cognitive dysfunction — 9 people ; diagnosis of neurological status was performed according to clinical protocols. Clinical and biochemical study was performed at the preoperative (3—5 days) and postoperative (5—7 days) stages: determined the content of superoxide dismutase, glutathione peroxidase, catalase in erythrocytes and α-tocopherol acetate in the serum of the blood, as well as the product cells: diene conjugates, metabolites of nitritanion in plasma. Variation statistics, probabilistic distribution of data with the subsequent estimation of reliability of results are applied; relative biochemical parameters were used: metabolic index, metabolic coefficient and metabolic effect for each. Standard methods using the program adapted to the “Excel” environment were used for calculations. The obtained data support the formation of patients with specific postoperative enzymatic-metabolic support of oxidative homeostasis, which should be considered as one of the triggers of hypoxic-ischemic brain lesions. In particular, at the level of the enzymatic chain of pro-, antioxidant protection and at the level of metabolic processes associated with peroxidation of phospholipids of cell membranes, a number of significant metabolic effects were revealed, which are generalized due to secondary oxidation products and NO‑dependent metabolites.

There is emerging evidence of a broad spectrum of neurological manifestations in COVID-19 patients. We report a case of a patient diagnosed with COVID-19 who presented bilateral lesions of the basal ganglia related to a severe acute respiratory distress syndrome. This observation allows expanding the neurological spectrum of COVID-19 particularly in patients with a more severe clinical course.

Approximately 15% of deaths in developed nations are due to sudden cardiac arrest, making it the most common cause of death worldwide. Though high-quality cardiopulmonary resuscitation has improved overall survival rates, the majority of survivors remain comatose after return of spontaneous circulation secondary to hypoxic ischemic injury. Since the advent of targeted temperature management, neurologic recovery has improved substantially, but the majority of patients are left with neurologic deficits ranging from minor cognitive impairment to persistent coma. Of those who survive cardiac arrest, but die during their hospitalization, some progress to brain death and others die after withdrawal of life-sustaining treatment due to anticipated poor neurologic prognosis. Here, we discuss considerations neurologists must make when asked, “Given their recent cardiac arrest, how much neurologic improvement do we expect for this patient?”

Annotation. The article presents the results of studying the symptomatology of different clinical variants of somatogenous asthenic symptom complex (SASC). The primary material of the study was a specially developed thematic map, the completion of which involved the implementation of clinical and anamnestic study and taking into account about 30 symptoms. Clinical and statistical methods were used: anamnestic quantitative analysis, variation statistics, probabilistic distribution of clinical signs with assessment of the reliability of the obtained results. It was found that in the structure of SASC the largest share belongs to the asthenic variant: is – 40.7%, while astheno-anxiety – 26.3%, astheno-subdepressive – 20.3%, and the smallest – dissomnic (12.7%). The symptomatic structure of SASC variants is characterized by the prevalence of the phenomena of physical and mental asthenia with symptoms of bodily synthesis, which allows to determine the most characteristic symptomatic complexes for cardiac surgery patients. The symptom complexes defined in research on each of variants of SASC allow to objectify at a preoperative stage a psychosomatic condition for maintenance of the integrated neurologic support of cardiosurgical patients.

Placental hypoxic-ischemic pathology is one of the common causes for adverse outcomes. But there is no commonly accepted evaluation system on specific morphological and histopathological measures of the placenta.This study aims to systematically select several core placental hypoxic-ischemic measures that have a high prognostic relevance to child health.We used data from the Collaborative Perinatal Project, a multicenter prospective cohort study that recruited over 55,000 pregnant women and followed their offspring to 7 years old. Women who had information on placental pathology and child outcomes were included. 57 placental measures considered to be relevant to hypoxia-ischemia were selected. Apgar score, intelligence quotient, preeclampsia, birth weight and subclinical neurology injuries were chosen as outcomes. The least absolute shrinkage and selection operator (LASSO) procedure as well as training and testing methods were used to select a more efficient and simpler placental hypoxic-ischemic measures that may have clinical implications.Of the 57 measures, 7 were selected as candidates by LASSO. Based on the training and testing methods, we retained placental measures with a higher odds ratio of child morbidity. We further narrowed down to four measures that had the highest prognostic relevance. They were: short cord length (ΣOR = 8.51), calcification of cut surface (ΣOR = 8.31), opaque membranes (ΣOR = 5.26), Hofbauer cells in terminal villi (ΣOR = 4.69).Our four-measure system is relatively simple and closely related to the child health. It may be used as a novel placental hypoxic-ischemic evaluation criterion, and function as the first line tool for future research.

Neonatal hypoxic-ischemic brain injury (HIBI) results in significant morbidity and mortality despite current standard therapies. MicroRNAs (miRNAs) are a promising therapeutic target; however, there is a paucity of data on endogenous miRNA expression of the brain after HIBI during the primary therapeutic window (6-72 h after injury).Postnatal day 9 mouse pups underwent unilateral carotid ligation+hypoxia (HIBI), sham surgery+hypoxia, or sham surgery+normoxia (controls). miRNA sequencing was performed on the ipsilateral brain of each of the three groups plus the contralateral HIBI brain at 24 and 72 h after injury. Findings were validated in eight key miRNAs by quantitative polymerase chain reaction.Hypoxia resulted in significant differential expression of 38 miRNAs at both time points. Mir-2137, -335, -137, and -376c were significantly altered by neonatal HIBI at 24 and 72 h, with 3 of the 4 demonstrating multiphasic expression (different direction of differential expression at 24 versus 72 h).Our global assessment of subacute changes in brain miRNA expression after hypoxia or HIBI will advance research into targeted miRNA-based interventions. It will be important to consider the multiphasic miRNA expression patterns after HIBI to identify optimal timing for individual interventions.This study is the first to comprehensively define endogenous brain microRNA expression changes outside of the first hours after neonatal hypoxic-ischemic brain injury (HIBI). Mir-2137, -335, -137, and -376c were significantly altered by neonatal HIBI and therefore deserve further investigation as possible therapeutic targets. The expression profiles described will support the design of future studies attempting to develop miRNA-based interventions for infants with HIBI. At 24 h after injury, contralateral HIBI miRNA expression patterns were more similar to ipsilateral HIBI than to controls, suggesting that the contralateral brain is not an appropriate "internal control" for miRNA studies in this model.

Aimed to investigate in an animal model the efficacy of humic acid by showing its antioxidant and anti-apoptotic effect comparing with the histopathological and neurological outcomes for the hypoxic-ischemic brain injury.28 Wistar-Albino rats who were on the 7th postnatal day and weighting between 9 and 19 g randomly divided into four groups with developed HIE model under the gas anesthesia. 20 mg/kg and 10 mg/kg intraperitoneal HA were given to Group I and II respectively. Saline was given to Group III and the sham group was Group IV. The brain tissues were stained with cresyl-violet histochemistry for grading neuronal cell injury and caspase immunohistochemistry.The neuronal cell injury was statistically lower in all neuroanatomical lands in HA treatment groups. The degree of ischemia was significantly smaller in HA groups. Caspase-3 immunoreactivity was decreased in the HA groups compared with the saline group. When the groups were compared, there were no serious neuronal injury in Group I.This is the first study which investigates the role of HA in HIE model. HA reduces apoptosis and neuronal injury in cerebral tissue of the rats. This findings suggest that HA may be viable protective agent against HIE.

This study aimed to explore the potential of real-time tissue elastography (RTE) in evaluating hepatic hypoxic-ischemic injury caused by brain death. We performed RTE and biopsy for 50 donated liver. Hematoxylin-eosin staining was used to observe hepatocyte acidophilic change. Liver grafts were divided into 2 groups, one nonacidophilic change (n = 7) and the other with acidophilic change (n = 43). Correlation and difference analysis were performed for hematoxylin-eosin staining results and RTE parameters. The result indicated that 4 of the 11 RTE parameters, namely, the area of low strain within the region of interest (%AREA), contrast (CONT), inverse difference moment (IDM), and correlation (CORR) were related to hepatocytes acidophilic change (r = 0.284, P = 0.046; r = 0.349, P = 0.013; r = −0.444, P = 0.001; r = −0.381, P = 0.00). Whereas %AREA and CONT of the nonacidophilic change group were lower than that of the acidophilic change group (P < 0.05), IDM and CORR in nonacidophilic change group were higher than that of the acidophilic change group (P < 0.05); the remaining parameters were not statistically different between 2 groups (P > 0.05). Analysis of receiver operating characteristic curve indicated that the area under the curve of %AREA, CONT, IDM, and CORR were 0.75, 0.79, 0.81, and 0.77, respectively. Based on this, we concluded that the quantitative analysis parameters of RTE could preliminary assess hepatic hypoxic-ischemic injury caused by brain death.

Erythropoietin is recognized as a pluripotent glycoprotein with unique biochemical and epigenetic properties that are important for fetal growth and development, as well as in critical conditions in subsequent periods of ontogenesis. In recent decades, researchers and clinicians have increased interest in the problem of the biological significance of erythropoietin, which can form the basis for constructing algorithms for early prognosis and diagnosis, optimizing the treatment of pathology of the perinatal period, including perinatal hypoxic-ischemic damage to the brain and spinal cord, which are at risk of disability and have a risk of disability significant role in neonatology and perinatal neurology.

The main reason for the development of neonatal hypoxic-ischemic encephalopathy is inadequate oxygen supply to brain tissue, due to a combination of hypoxemia and ischemia. Hypoxia leads to disruption of oxidative processes and the development of acidosis, decreased energy balance of the cell, an excess of excitatory neurotransmitters, impaired metabolism of glia and neurons. Excess homocysteine can also induce a cascade of events in hippocampal neurons, producing in response to acute bacterial meningitis and accumulating in the central nervous system, reaching neurotoxic levels. Understanding the pathological mechanisms of neonatal ischemic Brain injury will help optimize treatment and reduce the degree of hypoxic-ischemic damage. The purpose of the study was to assess the level of homocysteine in the blood serum as a predictor of the development of meningitis in newborns with hypoxic-ischemic lesions of the central nervous system using mathematical analysis. Material and methods. The following research methods were used in the course of work: clinical-anamnestic (subjective and objective examination data), laboratory (biochemical, immunological method, enzyme-linked immunosorbent assay method), instrumental (neurosonography), methods of mathematical statistics. Statistical processing of all obtained results performed on a personal computer using the license software package Statistics 13.0 (StatSoftInc, serial number JPZ8041382130ARCN10-J) and MS Excel. We used the following methods of statistical analysis in the study: descriptive statistics, parametric and nonparametric methods of comparison of mean groups, correlation analysis, multiple linear and logistic regression analysis, utility statistics: odds ratio, relative risk, ROC analysis. Results and discussion. The relationship between homocysteine and hemoglobin and gestational age was found to be direct and reversed with bilirubin. The use of linear regression analysis allowed predicting the value of homocysteine by known values of one or more predictor variables. A ROC analysis was performed to assess the diagnostic significance of homocysteine levels as an indicator of oxidative stress and to express it in some integral indicators. Conclusion. The analysis showed that high levels of homocysteine in newborns can be considered as a statistically significant indicator of oxidative stress and a predictor of meningitis in premature infants. The probability of developing meningitis in premature infants with high homocysteine levels is 1.15 times higher than in full-term infants with central nervous system lesions (p> 0.05) and 8 times higher (p

ZusammenfassungZiel dieser Studie ist es, ein kritisches postnatales Outcome als Prädiktor für die Entwicklung einer hypoxisch ischämischen Enzephalopathie (HIE) zu evaluieren. Methodik Auf Basis der Daten der hessischen Perinatalerhebung aus dem Jahr 2016 mit 52 122 Geburten (Lebendgeborene Einlinge, ≥ 37+0 Schwangerschaftswochen) wurden die Fälle mit kritischem Outcome identifiziert. Kriterien waren ein APGAR-Score 16,0 mmol/L. Diese Fälle wurden mit den HIE-Fällen aus der Neonatalerhebung zusammengeführt. Es wurden die Odds Ratio sowie Sensitivität/Spezifität und positiver (ppW)/negativer(npW) Vorhersagewert berechnet. Durch Evaluation des Geburtsverlaufes und des subpartalen CTG wurde die potentielle Vermeidbarkeit des Kritischen Outcomes/hypoxisch ischämischen Enzephalopathie überprüft. Ergebnisse Die Inzidenz der Fälle mit kritischem Outcome (n=11) und derer mit hypoxisch ischämischen Enzephalopathie (n=29) ist gering. Nach Zusammenführung der Daten aus der Perinatal- respektive Neonatalerhebung ergaben sich eine Sensitivität von 10,34%, eine Spezifität von 99,98%, ein positiver bzw. negativer prädiktiver Wert von 27,35, bzw. 99,95%. In nahezu einem Drittel der Fälle mit kritischem Outcome (4/11) oder hypoxisch ischämischen Enzephalopathie (9/29) fanden sich Hinweise auf eine potentielle Vermeidbarkeit. Schlussfolgerungen Ein postnataler Depressionszustand führt häufiger zur Diagnose einer HIE als eine schwere Azidose im Nabelschnurblut. Da ein Drittel der Fälle vermeidbar erscheinen, kann die fachübergreifende Einzelfallanalyse bei kritischem Neugeborenenstatus zur Optimierung der Geburtshilfe auch im Rahmen der externen Qualitätssicherung (QS) zielführend sein.

In hypoxic-ischemic encephalopathy, the neural progenitors (NPs) of the developing brain fail to replenish the oligodendrocyte progenitor cells lost during hypoxic-ischemic injury (HII). In this study, we aim to examine the influence of HII on the vulnerability of human NPs derived from human embryonic stem cells with regard to cell survival and oxidative stress, followed by assessment of cellular deregulation through measuring glutathione levels, basal calcium, glutamate release, and intracellular calcium ([Ca

Background: Hypoxic Ischemic Encephalopathy is defined as a heterogeneous, clinically defined syndrome characterized by disturbed neurologic function in the earliest days of life in a neonate. Proton MR spectroscopy could reveal brain ischemic injuries in asphyxiated neonates earlier than T1- or T2-weighted MR imaging. MR spectroscopy and MR imaging is very important for the diagnosis of hypoxic-ischemic injury. Patients and Methods: A cross-sectional study. From December 2018 to December 2019, 50 full-term neonates were admitted to Neonatal Care Unit (NCU) in Sohag University Hospital with signs of HIE and referred to the Radio Diagnosis Department for brain imaging. MR imaging studies were performed using MRI system 1.5 tesla Achieva, Philips superconductive MRI system. Our MRI sequences 1. Axial T1WI. 2. Axial T2WI. 3. Axial FLAIR. 4. Axial DWI. 5. proton MR spectroscopyResults: The study included 50 neonates; 7 of them had normal MRI findings. The other 43 neonates showed different patterns of injury; 24 neonates showed a central pattern of injury,11 neonates show peripheral patterns of injury, While the other 8 neonates had shown both central and peripheral patterns of brain injury. Only 45 of examined neonates shows abnormal lactate peak. The sensitivity of MRS is 100%. However, the specificity is low 70 %, the overall accuracy is 60 %. Conclusion: MR spectroscopy is an accurate, sensitive and non-invasive method for early detection of perinatal ischemic brain injuries

The purpose of current study was to explore the role and mechanism of microRNA-182-5p (miR182-5p) in neonatal hypoxic ischemic brain damage (HIBD). First, we established a hypoxic-ischemic (HI) rat model and assessed the neurological function of the rats using the Zea Longa score. Then, the level of miR-182-5p in brain tissue of neonatal rats was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Findings revealed that miR-182-5p was significantly down-regulated in the brain tissue of HI rat model. Next, we studied the target gene of miR-182-5p by using TargetScan and dual luciferase reporter assay. Results showed that CASP2 was a direct target gene of miR-182-5p, and the level of CASP2 was significantly up-regulated in the brain tissue of HI rat model. Immediately thereafter, we established an oxygen and glucose deprivation (OGD) cell model of primary cortical neurons, and demonstrated the changes of miR182-5p in cells treated with OGD by qRT-PCR. Finally, to determine the function of miR-182-5p in OGD subjected neuronal cells, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry (FCM) assays were used to study cell viability and apoptosis. The study found that compared with the OGD group, miR-182-5p mimic significantly increased nerve cell viability, reduced cell apoptosis and decreased cleaved-Caspase3/7/8 protein expression, however, all these changes were significantly reversed by overexpression of the CASP2 gene. Taken together, miR-182-5p might protect the nerve cells from ischemia and hypoxia by targeting CASP2, thereby playing a protective role in hypoxic ischemic encephalopathy, which might be a new effective target for neonatal hypoxic ischemic brain damage treatment.

Background: Methylphenidate (MPH) is a stimulant drug mainly prescribed to treat cognitive impairments in attention-deficit/hyperactivity disorder (ADHD). We demonstrated that neonatal hypoxia-ischemia (HI) induced attentional deficits in rats and MPH administration reversed these deficits. However, MPH effects on memory deficits after the HI procedure have not been evaluated yet. Aims: We aimed to analyze learning and memory performance of young hypoxic-ischemic rats after MPH administration and associate their performance with brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex and hippocampus. Methods: Male Wistar rats were divided into four groups ( n=11–13/group): control saline (CTS), control MPH (CTMPH), HI saline (HIS) and HIMPH. The HI procedure was conducted at post-natal day (PND) 7 and memory tasks between PND 30 and 45. MPH administration (2.5 mg/kg, i.p.) occurred 30 min prior to each behavioral session and daily, for 15 days, for the BDNF assay ( n=5–7/group). Results: As expected, hypoxic-ischemic animals demonstrated learning and memory deficits in the novel-object recognition (NOR) and Morris water maze (MWM) tasks. However, MPH treatment did not improve learning and memory deficits of these animals in the MWM—and even disrupted the animals’ performance in the NOR task. Increased BDNF levels were found in the hippocampus of HIMPH animals, which seem to have been insufficient to improve memory deficits observed in this group. Conclusions: The MPH treatment was not able to improve memory deficits resulting from the HI procedure considering a dose of 2.5 mg/kg. Further studies investigating different MPH doses would be necessary to determine a dose–response relationship in this model.

Background Hypoxia-ischemia (HI) is the most common cause of brain injury in newborns and the survivors often develop cognitive and sensorimotor disabilities that undermine the quality of life. In the current study, we examined the effectiveness of flupirtine, a potassium channel opener, shown previously in an animal model to have strong anti-neonatal-seizure efficacy, to provide neuroprotection and alleviate later-life disabilities caused by neonatal hypoxic-ischemic injury. Methods The rats were treated with a single dose of flupirtine for four days following HI induction in 7-day-old rats. The first dose of flupirtine was given after the induction of HI and during the reperfusion period. The effect of treatment was examined on acute and chronic brain injury, motor functions, and cognitive abilities. Results Flupirtine treatment significantly reduced HI-induced hippocampal and cortical tissue loss at acute time-point. Furthermore, at chronic time-point, flupirtine reduced contralateral hippocampal volume loss and partially reversed learning and memory impairments, but failed to improve motor deficits. Conclusion The flupirtine treatment regimen used in the current study significantly reduced brain injury at acute time-point in an animal model of neonatal hypoxic-ischemic encephalopathy. However, these neuroprotective effects were not persistent and only modest improvement in functional outcomes were observed at chronic time-points.

This study explored the hypothesis that late gestational reduction of corticosteroids transforms the cerebrovasculature and modulates postnatal vulnerability to mild hypoxic-ischemic (HI) injury. Four groups of Sprague-Dawley neonates were studied: 1) Sham-Control, 2) Sham-MET, 3) HI-Control, and 4) HI-MET. Metyrapone (MET), a corticosteroid synthesis inhibitor, was administered via drinking water from gestational day 11 to term. In Shams, MET administration 1) decreased reactivity of the hypothalamic-pituitary-adrenal (HPA) axis to surgical trauma in postnatal day 9 (P9) pups by 37%, 2) promoted cerebrovascular contractile differentiation in middle cerebral arteries (MCAs), 3) decreased compliance ≤46% and increased depolarization-induced calcium mobilization in MCAs by 28%, 4) mildly increased hemispheric cerebral edema by 5%, decreased neuronal degeneration by 66%, and increased astroglial and microglial activation by 10- and 4-fold, respectively, and 5) increased righting reflex times by 29%. Regarding HI, metyrapone-induced fetal transformation 1) diminished reactivity of the HPA axis to HI-induced stress in P9/P10 pups, 2) enhanced HI-induced contractile dedifferentiation in MCAs, 3) lessened the effects of HI on MCA compliance and calcium mobilization, 4) decreased HI-induced neuronal injury but unmasked regional HI-induced depression of microglial activation, and 5) attenuated the negative effects of HI on open-field exploration but enhanced the detrimental effects of HI on negative geotaxis responses by 79%. Overall, corticosteroids during gestation appear essential for normal cerebrovascular development and glial quiescence but induce persistent changes that in neonates manifest beneficially as preservation of postischemic contractile differentiation but detrimentally as worsened ischemic cerebrovascular compliance, increased ischemic neuronal injury, and compromised neurobehavior.

Perinatal hypoxic-ischemic-encephalopathy significantly contributes to neonatal death and life-long disability such as cerebral palsy. Advances in signal processing and machine learning have provided the research community with an opportunity to develop automated real-time identification techniques to detect the signs of hypoxic-ischemic-encephalopathy in larger electroencephalography/amplitude-integrated electroencephalography data sets more easily. This review details the recent achievements, performed by a number of prominent research groups across the world, in the automatic identification and classification of hypoxic-ischemic epileptiform neonatal seizures using advanced signal processing and machine learning techniques. This review also addresses the clinical challenges that current automated techniques face in order to be fully utilized by clinicians, and highlights the importance of upgrading the current clinical bedside sampling frequencies to higher sampling rates in order to provide better hypoxic-ischemic biomarker detection frameworks. Additionally, the article highlights that current clinical automated epileptiform detection strategies for human neonates have been only concerned with seizure detection after the therapeutic latent phase of injury. Whereas recent animal studies have demonstrated that the latent phase of opportunity is critically important for early diagnosis of hypoxic-ischemic-encephalopathy electroencephalography biomarkers and although difficult, detection strategies could utilize biomarkers in the latent phase to also predict the onset of future seizures.

Neonatal hypoxic-ischemic encephalopathy (HIE) often leads to neonatal death or severe, irreversible neurological deficits. Pathologically, the occurrence of massive cell death and subsequent inflammation suggested that pyroptosis, an inflammation associated programed cell death, might play a role in HIE. Here, by measuring changes of key molecules in pyroptosis pathway in HIE patients, we discovered that their elevation levels tightly correlate with the severity of HIE. Next, we demonstrated that application of MCC950, a small molecule to inhibit NLRP3 inflammasome and thus pyroptosis, substantially alleviated pyroptosis and the injury severity in rats with neonatal hypoxic-ischemic brain damage (HIBD). Mechanistically, we showed that NLRP-3/caspase-1/GSDMD axis is required for microglia pyroptosis and activation. Our data demonstrated that microglia mediated pyroptosis played a crucial role in neonatal HIE, which shed lights into the development of intervention avenues targeting pyroptosis to treat HIE and traumatic brain injuries.

Objective Hypoglycemia is a significant risk factor for perinatal brain injury and adverse outcomes, particularly in infants requiring resuscitation following hypoxic ischemic (HI) insult. We aimed to study blood glucose (BG) levels in physiologically stressed infants in the presence or absence of epinephrine (Epi) administration at resuscitation in the first 24 hours after birth. Study Design A retrospective chart review of all infants with heart rate (HR) Results By design, infants in the Epi group had lower cord pH and higher base deficit. BG was significantly lower overtime in premature infants ≤32 weeks of gestation in the Epi group. The BG was markedly higher in near-term and term infants in the Epi group compared with the PPV group. Hypoglycemia was more common despite administration of higher GIR in premature infants ≤32 weeks of gestation. Conclusion In the presence of physiological stress, premature infants are more at risk for hypoglycemia than term infants.

Background and Purpose: Despite the advances in treating neonatal hypoxic-ischemic encephalopathy (HIE) with induced hypothermia, the rates of severe disability are still high among survivors. Preclinical studies have indicated that cell therapies with hematopoietic stem/progenitor cells could improve neurological outcomes in HIE. In this study, we investigated whether the administration of AMD3100, a CXCR4 antagonist that mobilizes hematopoietic stem/progenitor cells into the circulation, has therapeutic effects in HIE. Methods: P10 Wistar rats of both sexes were subjected to right common carotid artery occlusion or sham procedure, and then were exposed to hypoxia for 120 minutes. Two subcutaneous injections of AMD3100 or vehicle were given on the third and fourth day after HIE. We first assessed the interindividual variability in brain atrophy after experimental HIE and vehicle treatment in a small cohort of rats. Based on this exploratory analysis, we designed and conducted an experiment to test the efficacy of AMD3100. Brain atrophy on day 21 after HIE was defined as the primary end point. Secondary efficacy end points were cognitive (T-water maze) and motor function (rotarod) on days 17 and 18 after HIE, respectively. Results: AMD3100 did not decrease the brain atrophy in animals of either sex. Cognitive impairments were not observed in the T-water maze, but male hypoxic-ischemic animals exhibited motor coordination deficits on the rotarod, which were not improved by AMD3100. A separate analysis combining data from animals of both sexes also revealed no evidence of the effectiveness of AMD3100 treatment. Conclusions: These results indicate that the subacute treatment with AMD3100 does not improve structural and functional outcomes in a rat HIE model.

Hypoxic-ischemic brain damage (HIBD) is a leading cause of fatality and neural system injury in neonates. This study aims to explore the effect of long noncoding RNA H19 on cardiomyocyte apoptosis in neonatal rats with HIBD. The neonatal rat model of HIBD was established. The cerebral infarction volume and apoptosis index of cardiomyocyte increased, while H19 expression decreased in neonatal rats with HIBD. After the lentivirus vector of overexpressed H19 was injected into neonatal rats with HIBD, the cardiomyocyte apoptosis was suppressed; levels of inflammatory factors and oxidative stress injury of myocardial tissues were reduced. The binding relationships between H19 and miR-149-5p, and miR-149-5p and leukemia inhibitory factor (LIF) were predicted by a bioinformatics website and verified using the dual-luciferase reporter gene assay. H19 competitively bound to miR-149-5p to upregulate LIF expression and activate the PI3K/Akt pathway. Moreover, a functional rescue experiment was carried out. Injection of Wortmannin reversed the inhibitory effect of H19 overexpression on cardiomyocyte apoptosis in neonatal rats with HIBD. It could be concluded that H19 competitively bound to miR-149-5p to upregulate LIF expression and activate the PI3K/Akt pathway, thus reducing cardiomyocyte apoptosis in neonatal rats with HIBD. This study may offer new insights for HIBD treatment.

Lepidium meyenii (Maca) is an annual or biennial herb from South America that is a member of the genus Lepidium L. in the family Cruciferae. This herb has antioxidant, anti-apoptotic, and enhances autophagy functions and can prevent cell death, and protect neurons from ischemic damage. Macamide B, an effective active ingredient of maca, has a neuroprotective role in neonatal hypoxic-ischemic brain damage (HIBD), and the underlying mechanism of its neuroprotective effect is not yet known. The purpose of this study is to explore the impact of macamide B on HIBD-induced autophagy and apoptosis and its potential mechanism for neuroprotection. The modified Rice-Vannucci method was used to induce HIBD on 7-day-old (P7) macamide B and vehicle-pretreated pups. TTC staining was used to evaluate the cerebral infarct volume of pups, brain water content was measured to evaluate the neurological function of pups, neurobehavioral testing was used to assess functional recovery after HIBD, TUNEL and FJC staining was used to detect cell autophagy and apoptosis, and western blot analysis was used to detect the expression levels of the pro-survival signaling pathway phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and autophagy and the apoptosis-related proteins. The results show that macamide B pretreatment can significantly decrease brain damage, improve the recovery of neural function after HIBD. At the same time, macamide B pretreatment can induce the activation of PI3K/AKT signaling pathway after HIBD, enhance autophagy, and reduce hypoxic-ischemic (HI)-induced apoptosis. In addition, 3-methyladenine (3-MA), an inhibitor of PI3K/AKT signaling pathway, significantly inhibits the increase in autophagy levels, aggravates HI-induced apoptosis, and reverses the neuroprotective effect of macamide B on HIBD. Our data indicate that macamide B pretreatment might regulate autophagy through PI3K/AKT signaling pathway, thereby reducing HIBD-induced apoptosis and exerting neuroprotective effects on neonatal HIBD. Macamide B may become a new drug for the prevention and treatment of HIBD.

Maternal e-cigarette (e-cig) exposure is a pressing perinatal health concern. Emerging evidence reveals its potential adverse impacts on brain development in offspring, yet the underlying mechanisms are poorly understood. The present study tested the hypothesis that fetal e-cig exposure induces an aberrant DNA methylation profile in the developing brain, leading to alteration of autophagic flux signaling and programming of a sensitive phenotype to neonatal hypoxic-ischemic encephalopathy (HIE). Pregnant rats were exposed to chronic intermittent e-cig aerosol. Neonates were examined at the age of 9 days old. Maternal e-cig exposure decreased the body weight and brain weight but enhanced the brain-to-body weight ratio in the neonates. E-cig exposure induced a gender-dependent increase in hypoxic-ischemia-induced brain injury in male neonates associated with enhanced reactive oxygen species (ROS) activity. It differentially altered DNA methyltransferase expression and enhanced both global DNA methylation levels and specific CpG methylation at the autophagy-related gene 5 (ATG5) promoter. In addition, maternal e-cig exposure caused downregulations of ATG5, microtubule-associated protein 1 light chain 3β, and sirtuin 1 expression in neonatal brains. Of importance, knockdown of ATG5 in neonatal pups exaggerated neonatal HIE. In conclusion, the present study reveals that maternal e-cig exposure downregulates autophagy-related gene expression via DNA hypermethylation, leading to programming of a hypoxic-ischemic sensitive phenotype in the neonatal brain.

Background White matter injury is a common ischemic brain injury in premature infants and for which there is no effective treatment. Stem cell transplantation has emerged as a novel approach for replacing damaged brain tissues and promoting regenerative processes. Since intracerebral transplantation is not clinically feasible for premature infants, intranasal delivery of cells to the brain is a promising, noninvasive therapeutic approach for restoring the damaged brain. This study was conducted to investigate whether transplanted human oligodendrocyte progenitor cells exhibit neuroprotective effects in a rat model of WMI in premature infants. Methods SD rats aged 3 days were randomly divided into sham group, preterm white matter injury group and nasal transplantation group. Hypoxia–ischemia was induced in 3-day-old rat pups by right carotid artery ligation, followed by exposure to 6% oxygen for 90 min. Rats were intranasally administered the cell suspension (250,000 cells in 6 µL) twice in each nostril (1 × 106 cells total), and myelin basic protein immunofluorescence staining and transmission electron microscopy were performed to assess endogenous myelin growth in the right hemispheres. Behavioral tests, including the Morris water maze, adhesive-removal test, and cylinder rearing test, as well as a gait test, were performed to evaluate the therapeutic effects at 12 weeks after transplantation. Results The cells transplanted from the nose can enter brain tissue of rats 3 days after transplantation. The myelin sheath structure was more compact and the myelin sheath thickness was increased. The nerve function defect was improved 12 weeks after transplantation. Conclusions The intranasal administration of human oligodendrocyte progenitor cells had beneficial therapeutic effects on rehabilitation of the rat hypoxia-ischemia model. This technique is a potential strategy for applying oligodendrocyte progenitor cells in transplantation therapy against white matter injury.

Neonatal hypoxic–ischemic encephalopathy is a notable cause of neonatal death and developmental disabilities. To achieve better outcomes, it is important in treatment strategy selection to categorize the degree of hypoxia ischemia and evaluate dose response. In an asphyxia piglet model with histopathological brain injuries that we previously developed, animals survived 5 days after insult and showed changes in cerebral blood volume (CBV) that reflected the severity of injuries. However, little is known about the relationship between changes in CBV during and after insult. In this study, an HI event was induced by varying the amount and timing of inspired oxygen in 20 anesthetized piglets. CBV was measured using near-infrared time-resolved spectroscopy before, during, and 6 h after insult. Change in CBV was calculated as the difference between the peak CBV value during insult and the value at the end of insult. The decrease in CBV during insult was found to correlate with the increase in CBV within 6 h after insult. Heart rate exhibited a similar tendency to CBV, but blood pressure did not. Because the decrement in CBV was larger in severe HI, the CBV increment immediately after insult is considered useful for assessing degree of HI insult.

Neonatal hypoxic ischemic encephalopathy (HIE) endangers quality of life in children; but effective cure is rare. Neurogenesis plays an important role in neural repair following brain damage. Recent studies have demonstrated that telomerase reverse transcriptase (TERT) was involved in neurogenesis regulation. However, whether TERT participates in the regulation of neurogenesis after hypoxic-ischemic brain damage (HIBD) is unclear. Here, we established a model of HIBD in neonatal rats both in vivo and in vitro, and used lentivirus and adenovirus transfection for TERT overexpression to investigate its role in neurogenesis after HIBD in developmental stage. Using immunofluorescence staining, cell counting Kit-8 staining, TUNEL, and western blotting, we observed that TERT attenuated apoptosis and promoted proliferation, migration, and differentiation in neural stem cells (NSCs). Furthermore, TERT induced myelination in the brain of neonatal rats after HIBD. Neurobehavioral tests revealed that TERT could improve learning, memory, and neurological function after HIBD in neonatal rats, and thus promote the recovery of neurological function after HIBD. In addition, we investigated the regulatory mechanism of TERT during neurogenesis after HIBD in developmental stage. We found that TERT may regulate neurogenesis after HIBD through the Sonic Hedgehog/Gli1 signaling pathway. Our study demonstrated that TERT could promote neural repair and neurological function recovery after HIBD in neonatal rats. The new neuroprotective pathway regulated by TERT during HIBD described here could provide a basis for developing therapeutic strategy for neonatal HIE. Furthermore, TERT may be a potential target during neural repair and reconstruction in various diseases affecting nervous system.

Hypoxic ischemic insult in early childhood can have a varied clinical presentation depending on the timing and severity of the insult, and magnetic resonance imaging plays a key role in identifying injury patterns. Dyskinetic cerebral palsy is commonly associated with injury to the basal ganglia and thalamus. We report two cases presenting in early childhood with signs and symptoms of dyskinetic cerebral palsy attributed to focal damage to the superior cerebellar vermis secondary to a hypoxic insult in the perinatal period in term infants.

To achieve better outcomes in hypoxic-ischemic encephalopathy, categorizing the degree of the hypoxia-ischemia (HI) is important for selecting suitable candidates for therapeutic hypothermia and any additional treatment strategies. We previously developed a novel model of asphyxiated piglets with a uniform degree of histopathological brain injuries that survived for 5 days after insult and showed changes in cerebral blood volume (CBV) that reflected the severity of the brain injuries. However, little is known about the relationship between changes in CBV during and after insult. In this study, an HI event was induced by low inspired oxygen in 23 anesthetized newborn piglets, including three sham controls. CBV was measured using near-infrared time-resolved spectroscopy (TRS). Data were collected before, during, and 6 h after insult. The change in CBV was calculated as the difference between the peak CBV value during insult and the value at the end of insult. The decrease in CBV during insult was found to correlate with the increase in CBV within 6 h after insult. Heart rate exhibited a similar tendency to CBV but blood pressure did not. The CBV increment immediately after resuscitation provides a relatively precise prediction of the severity of HI insult.

Therapeutic hypothermia (TH) is a powerful neuroprotective strategy that has provided robust evidence for neuroprotection in pre-clinical studies of neurological disorders. Despite strong pre-clinical evidence, TH has not shown efficacy in clinical trials of most neurological disorders. The only successful trials employing therapeutic hypothermia were related to cardiac arrest in adults and hypoxic ischemic injury in neonates. Further investigations into the parameters of its use, and study design comparisons between pre-clinical and clinical studies, are warranted. This article demonstrates two methods of short-duration hypothermia induction. The first method allows for rapid hypothermia induction in rats using ethanol spray and fans. This method works by cooling the skin, which has been less commonly used in clinical trials and may have different physiological effects. Cooling is much more rapid with this technique than is achievable in human patients due to differences in surface area to volume ratio. Along with this, a second method is also presented, which allows for a clinically achievable cooling rate for short-duration hypothermia. This method is easy to implement, reproducible and does not require active skin cooling.

Hypoxic-ischemic brain damage (HIBD) is one of the most common critical diseases in neonates with high mortality and disability rates. The latest research showed that long non-coding RNAs(lncRNA) played an important role in the development of HIBD. Recently, acupuncture therapy has been found to be effective in the treatment of HIBD. However, the mechanism of lncRNA in acupuncture treatment of HIBD is still unclear. In this study, we investigated the role of lncRNA in acupuncture treatment of HIBD in detail. We demonstrated behavioral performance similar to cognitive deficits in HIBD rat models in the new object recognition experiment and pathological lesion of the prefrontal cortex in nissl staining. Acupuncture treatments at acupoints DU24 and GB13 was proved to be effective in alleviating behavioral deficits and brain injury. A whole transcriptome analysis was applied to investigate transcriptome changes caused by acupuncture in PFC of HIBD rats. A total of 48 mRNAs and 65 lncRNAs was identified relate to acupuncture group and model group. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, we found several lncRNAs and their target mRNAs were related to PI3K-Akt signaling pathway, TNF signaling pathway and NOD-like receptor signaling pathway, etc. The results of our research may provide new perspectives on the mechanism of acupuncture and affect the diagnosis and treatment of HIBD.

Ischemic stroke is a major cause of long-term disabilities, including vision loss. Neuronal and blood vessel maturation can affect the susceptibility of and outcome after ischemic stroke. Although we recently reported that exposure of neonatal mice to hypoxia–ischemia (HI) severely compromises the integrity of the retinal neurovasculature, it is not known whether juvenile mice are similarly impacted. Here we examined the effect of HI injury in juvenile mice on retinal structure and function, in particular the susceptibility of retinal neurons and blood vessels to HI damage. Our studies demonstrated that the retina suffered from functional and structural injuries, including reduced b-wave, thinning of the inner retinal layers, macroglial remodeling, and deterioration of the vasculature. The degeneration of the retinal vasculature associated with HI resulted in a significant decrease in the numbers of pericytes and endothelial cells as well as an increase in capillary loss. Taken together, these findings suggest a need for juveniles suffering from ischemic stroke to be monitored for changes in retinal functional and structural integrity. Thus, there is an emergent need for developing therapeutic approaches to prevent and reverse retinal neurovascular dysfunction with exposure to ischemic stroke.

Neonatal encephalopathyis defined as aclinical syndrome presenting with analtered level of consciousness or epilepsy, and usually associated with difficulty withi nitiating and maintaining respiration, abnormal sensorium andr eflexes.Neonatal encephalopathy is the third leading cause of under 5 years mortality and contributes substantially to long-term neurological morbidity world-wide.MRI is the method of choice that plays apivotal role in the diagnostic evaluation of patients presented by clinical picture of neonatal encephalopathy.The adding of advanced techniques, such as DWI/ADC, magnetic resonance spectroscopy (MRS) and magnetic resonance angiography (MRA) can improve the accuracy of diagnoses.Over the years, the term “neonatal encephalopathy”, has been used by many as asynonym of “Hypoxic-ischemic encephalopathy”, on the ground that it is the most common cause of neonatal encephalopathy, for that reason it is important to emphasize that many different processes leading to neonatal encephalopathy may develop prenatally, at birth or immediately post-delivery and result from mainly, but not exclusively, vascular, genetic, metabolic, infectious, and traumatic processes, most of them are treatable if they are early diagnosed, while their treatment may be hindered by the assumption that the diagnosis is HIE.

Hypoxic–ischemic injury (HII) at birth has been found to relate to differences in development, including decreased memory performance. The current study assessed recognition memory in 6- and 12-month-old HII infants and typically developing (TD) infants using two eye-tracking paradigms well suited to explore explicit memory processes early in life: visual paired comparison (VPC) and relational memory (RM). During the VPC, infants were familiarized to a face and then tested for their novelty preference immediately and after a two-minute delay. At 6 months, neither HII nor TD showed a VPC novelty preference at immediate delay, but at 12 months, both groups did; after the two-minute delay, no group showed a novelty preference. During RM, infants were presented with blocks containing a learning phase with three different scene–face pairs, and a test phase with one of the three scenes and all three faces appearing simultaneously. When there was no interference from other scene–face pairs between learning and test, 6-month-old TD showed evidence of an early novelty preference, but when there was interference, they revealed an early familiarity preference. For 12-month-old TD, some evidence for a novelty preference during RM was seen regardless of interference. Although HII and TD showed similar recognition memory on the VPC, when looking at RM, HII infants showed subtle differences in their attention to the familiar and novel faces as compared to their TD peers, suggesting that there might be subtle differences in the underlying memory processing mechanisms between HII and TD. More work is needed to understand how these attentional patterns might be predictive of later memory outcomes.

Background: Microglial cells play an important role in the immune system in the brain. Activated microglial cells are not only injurious but also neuroprotective. We confirmed marked lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression in microglial cells in pathological lesions in the neonatal hypoxic-ischemic encephalopathy model brain. LOX-1 is known to be an activator of cytokines and chemokines through intracellular pathways. Here, we investigated a novel role of LOX-1 in microglial cells under hypoxic and ischemic conditions. Methods: We isolated primary rat microglial cells from 3-day-old Sprague-Dawley rat brains and confirmed that the isolated cells showed more than 98% Iba-1 positive with immunocytochemistry. We performed oxygen glucose deprivation (OGD) treatment of primary rat microglial cells as an in vitro model of nHIE. Then, we evaluated the expression levels of LOX-1, cytokines and chemokines with or without siRNA and inhibitors, compared with no OGD-treated cells. In addition, we analyzed reactive oxygen species and cell viability.Results: We found that defects in oxygen and nutrition induced LOX-1 expression and led to the production of inflammatory mediators, such as the cytokines IL-1β, IL-6 and TNF-α, the chemokines CCL2, CCL5 and CCL3 and reactive oxygen/nitrile species. Then, the LOX-1 signal transduction pathway was blocked by inhibitors, LOX-1 siRNA, the p38-MAPK inhibitor SB203580 and the NF-κB inhibitor BAY11-7082 suppressed the production of the inflammatory mediators. Moreover, we demonstrated that LOX-1 in microglial cells was autonomously overexpressed by positive feedback of the intracellular LOX-1 pathway. Conclusion: The hypoxic/ischemic conditions of microglial cells induced LOX-1 expression and activated immune system. We revealed one of the LOX-1 signaling pathways in microglia and provide a hint of a new treatment strategy for nHIE. It was speculated that Microglial cells are known to contribute to various neurological diseases. Hypoxic and ischemic brain injuries result in lifelong neurological and mental deficiency. LOX-1 and its related molecules or chemicals may be major therapeutic candidates.

BackgroundAcute hypoxic-ischemic brain damage (HIBD) occurs not only in newborns but also in adults. It is associated with series of cellular and biochemical pathways that lead to neuronal injury. N-3 polyunsaturated fatty acids (PUFAs) have been reported to improve neuron functions via G protein-coupled receptor 120 signal pathway in cells or with exogenous supplementation. Possible protective targets and underlying mechanisms of high proportion of n-3/n-6 PUFAs contained in the brains of mfat-1 transgenic mice on HIBD-induced adult brain damage needed to be further investigated.MethodsThe adult C57BL/6J (WT) and mfat-1 transgenic mice adopted HIBD model. A gas chromatograph was used to determine the composition of PUFAs. Neurological deficit scores test, TTC staining and Nissl staining were employed to evaluate the neuroprotective effects. Cleaved-caspase3 and TUNEL experiment were used to detect apoptosis after injury. Inflammatory factors were detected by ELISA assay. RNA-sequencing analysis was processed and the differential expressed genes were verified by real-time quantitative PCR. Key factors related to inflammation were detected by immunofluorescence and western blot.ResultsThe mfat-1 transgenic mice with high ratio of n-3/n-6 PUFAs in brain tissues were showed to have protective effects on HIBD-induced brain damage by reduced infarct range and greatly improved neurobehavioral defects. Further analysis revealed that the level of neuronal necrosis, apoptosis and inflammation induced by brain injury were relatively low. RNA-seq analysis showed multiple pathways and targets involved in this process. Significant activation of GPR120, reduction of phosphorylation of TAK1 and NF-κB P65 in the downstream of the pro-inflammatory pathway were found in the brains of mfat-1 mice on HIBD. ConclusionsThe study showed that mfat-1 transgenic mice had protective effects on HIBD-induced brain injury by multiple pathways. Activation of GPR120 and reduction of related pro-inflammatory pathway involved in this process, which may improve or prevent dangerous perioperative and postoperative complications, innovate clinical intervention strategy and potentially benefit more patients.

To investigate the application value of magnetic resonance diffusion kurtosis imaging (DKI) in hypoxic–ischemic brain damage (HIBD) in newborn piglets and to compare imaging and pathological results. Of 36 piglets investigated, 18 were in the experimental group and 18 in the control group. The HIBD model was established in newborn piglets by ligating the bilateral common carotid arteries and placing them into hypoxic chamber. All piglets underwent conventional MRI and DKI scans at 3, 6, 9, 12, 16, and 24 h postoperatively. Mean kurtosis (MK) and mean diffusivity (MD) maps were constructed. Then, the lesions were examined using light and electron microscopy and compared with DKI images. The MD value of the lesion area gradually decreased and the MK value gradually increased in the experimental group with time. The lesion areas gradually expanded with time; MK lesions were smaller than MD lesions. Light microscopy revealed neuronal swelling in the MK- and MD-matched and mismatched regions. Electron microscopy demonstrated obvious mitochondrial swelling and autophagosomes in the MK- and MD-matched region but normal mitochondrial morphology or mild swelling in the mismatched region. DKI can accurately evaluate early ischemic–hypoxic brain injury in newborn piglets.

Diagnosis of hypoxic-ischemic encephalopathy (HIE) is currently limited and prognostic biological markers are required for early identification of at risk infants at birth. Using pre-clinical data from our fetal sheep models, we have shown that micro-scale EEG patterns, such as high-frequency spikes and sharp waves, evolve superimposed on a significantly suppressed background during the early hours of recovery (0-6 h), after an HI insult. In particular, we have demonstrated that the number of micro-scale gamma spike transients peaks within the first 2-2.5 hours of the insult and automatically quantified sharp waves in this period are predictive of neural outcome. This period of time is optimal for the initiation of neuroprotection treatments such as therapeutic hypothermia, which has a limited window of opportunity for implementation of 6 h or less after an HI insult. Clinically, it is hard to determine when an insult has started and thus the window of opportunity for treatment. Thus, reliable automatic algorithms that could accurately identify EEG patterns that denote the phase of injury is a valuable clinical tool. We have previously developed successful machine-learning strategies for the identification of HI micro-scale EEG patterns in a preterm fetal sheep model of HI. This paper employs, for the first time, reverse biorthogonal Wavelet-Scalograms (WS) as the inputs to a 17-layer deep-trained convolutional neural network (CNN) for the precise identification of high-frequency micro-scale spike transients that occur in the 80-120Hz gamma band during first 2 h period of an HI insult. The rbio-WS-CNN classifier robustly identified spike transients with an exceptionally high-performance of 99.82%.Clinical relevance—The suggested classifier would effectively identify and quantify EEG patterns of a similar morphology in preterm newborns during recovery from an HI-insult.