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In the proposed systematic review, we seek to identify, compile, examine, and synthesize the findings of quantitative and mixed methods research in which both brain imaging techniques and assessments of achievement have been used to evaluate and understand the relationships among developmental programming , neurodevelopment and achievement in reading and mathematics. The principal aims of the present review are to provide an accurate, concise, and accessible overview of the major findings of literature in the field and at the same time address the following research questions: (1) What is the current state of the evidence concerning the relationships among developmental programming, neurodevelopment and achievement in reading and mathematics? (2) What trends can be observed in the extant literature? (3) What gaps exist in the in the extant literature? (4) What are appropriate directions for future research?

Diffusion-time- ( td) dependent diffusion MRI (dMRI) extends our ability to characterize brain microstructure by measuring dMRI signals at varying td. The use of oscillating gradient (OG) is essential for accessing short td but is technically challenging on clinical MRI systems. This study aims to investigate the clinical feasibility and value of td-dependent dMRI in neonatal hypoxic-ischemic encephalopathy (HIE). Eighteen HIE neonates and six normal term-born neonates were scanned on a 3 T scanner, with OG-dMRI at an oscillating frequency of 33 Hz (equivalent td ≈ 7.5 ms) and pulsed gradient (PG)-dMRI at a td of 82.8 ms and b-value of 700 s/mm2. The td-dependence, as quantified by the difference in apparent diffusivity coefficients between OG- and PG-dMRI (ΔADC), was observed in the normal neonatal brains, and the ΔADC was higher in the subcortical white matter than the deep grey matter. In HIE neonates with severe and moderate injury, ΔADC significantly increased in the basal ganglia (BG) compared to the controls (23.7% and 10.6%, respectively). In contrast, the conventional PG-ADC showed a 12.6% reduction only in the severe HIE group. White matter edema regions also demonstrated increased ΔADC, where PG-ADC did not show apparent changes. Our result demonstrated that td-dependent dMRI provided high sensitivity in detecting moderate-to-severe HIE.

Introduction: Among the hypertensive pathologies of pregnancy, preeclampsia remains the entity responsible for pregnancy complications. Objective: The aim of this work was to determine the frequency of hypertensive pathologies in the peripartum, to determine the maternal and neonatal morbidity factors associated with preeclampsia on the one hand, and on the other hand, to other forms of hypertension in the peripartal period. Patients and methods: This is a cross-sectional study of hypertensive pathologies in per partum over a period of 15 months which have been included any pregnant, parturient and hypertensive childbirth. The data was analyzed using SPSS software version 21.0. Data positioning and dispersion parameters were studied. The factor analysis was performed by determining the odds ratio with a 95% confidence interval and a significance level set at p ≤ 0.05. Results: 142 cases of hypertension were collected from a total of 2988 deliveries, i.e. a frequency of hypertension of 4.8%. The main form of high blood pressure (HBP) was the isolated HBP at 51.4%. 60.3% of primiparas were preeclamptic [OR 2.47 (CI 1.25 - 4.91)], 63.2% of preeclampsia did not follow prenatal consultations [OR 2.43 (CI 1.06 - 5.62)], 63.6% of preeclampsia had moderate and severe threat premature delivery [OR 4.57 (CI 2.11 - 9.99)], neonatal hypoxia in the fifth minute was found in 34.4% of newborns of preeclamptic mothers [OR 3.02 (CI 1.44 - 6.34)], hypotrophy was observed in 41.4% of the cases in the preeclamptic patients [OR 5.41 (IC 1, from 55 to 19.57)]. Conclusion: Preeclampsia is significantly associated with maternal and neonatal morbidity.

Neonatal hypoxia-ischemia (HI) is responsible for movement disorders in preterm infants. Non-pharmacological strategies, such as environmental enrichment (EE) during adulthood, have shown positive effects on promoting sensorimotor recovery after HI. However, little is known about the effects of perinatal EE on sensorimotor function following HI. In present study we investigated the hypothesis that enriched experiences during pregnancy and lactation would reduce motor impairments caused by a model of neonatal HI in rats. At postnatal day (PND) 3, Wistar pups of both sexes were subject to the modified Rice-Vannucci model. Motor function was evaluated from PND 60 to PND 64. HI caused a reduction in the forepaws strength and worsening of movement quality in the right forepaw. These effects were attenuated in animals receiving prenatal or lactational EE, which showed better performance when compared to the control group. Moreover, enriched experiences during lactation reversed HI-induced asymmetric use of the forepaws and the trend to increased paw errors in a walking test. Lower scores were found in the contralateral forepaw placement in HI animals, except when EE was provided at both stages of neurodevelopment . These results indicate that enriched experiences reduce motor impairments, i.e , measured in force, asymmetry and coordination domains, and that EE during lactation is more effective in promoting post-injury recovery. These data support that early therapeutic interventions might enhance functional reorganization at a period of high brain plasticity and that enriched-like experience might be encouraged in pediatric rehabilitation programs, in order to reduce long-term movement disorders after neonatal brain insults.

Vaisiaus kraujagyslių pirmeiga (VKP) yra labai reta patologija, kurios nediagnozavus laiku, dėl didelės naujagimių hipoksijos ir nukraujavimo rizikos smarkiai sumažėja naujagimių išgyvenamumas. Prenatalinė VKP diagnozė ir tinkamai pasirinktas cezario pjūvio operacijos laikas yra būdas išvengti nepalankios nėštumo baigties. Šiuo metu nėra pakankamai aukšto lygio mokslinių įrodymų dėl virkštelės tvirtinimosi vietos nustatymo įtraukimo į standartinį ultragarsinio tyrimo protokolą. Straipsnyje pristatomas prenataliai nediagnozuotos VKP atvejis ir pateikiama literatūros apžvalga.

The connection between early brain injury and subsequent development of disorders is unknown. Neonatal hypoxia-ischemia (HI) alters circuits associated with subplate neurons (SPNs). SPNs are among the first maturing cortical neurons, project to thalamorecipient layer 4 (L4), and are required for the development of thalamocortical connections. Thus, early HI might influence L4 and such influence might persist. We investigated functional circuits to L4 neurons in neonatal rat HI models of different severities (mild and moderate) shortly after injury and at adolescence. We used laser-scanning photostimulation in slices of auditory cortex during P5–10 and P18–23. Mild injuries did not initially (P6/P7) alter the convergence of excitatory inputs from L2/3, but hyperconnectivity emerged by P8–10. Inputs from L4 showed initial hypoconnectivity which resolved by P8–10. Moderate injuries resulted in initial hypoconnectivity from both layers which resolved by P8–10 and led to persistent strengthening of connections. Inhibitory inputs to L4 cells showed similar changes. Functional changes were mirrored by reduced dendritic complexity. We also observed a persistent increase in similarity of L4 circuits, suggesting that HI interferes with developmental circuit refinement and diversification. Altogether, our results show that neonatal HI injuries lead to persistent changes in intracortical connections.

Electronic FHR monitoring is already widely used for antenatal fetal monitoring and labor observation. It is believed to be able to reduce the risk of intrauterine fetal hypoxia and decrease the probability of neonatal hypoxia and the neonatal mortality rate. In 2002, 85% of 3.4 million pregnant women in the United States received electronic FHR monitoring during labor. At present, continuous electronic FHR monitoring has become the most widely used obstetric monitoring technology.

The recently developed oscillating-gradient diffusion MRI (OG-dMRI) technique extends our ability to examine brain structures at different spatial scales. In this study, we investigated the sensitivity of OG-dMRI in detecting cellular and subcellular structural changes in a mouse model of neonatal hypoxia ischemia (HI). Neonatal mice received unilateral HI injury or sham injury at postnatal day 10, followed by in vivo T2-weighted and diffusion MRI of the brains at 3–6 h and 24 h after HI. Apparent diffusion coefficient (ADC) maps were acquired using conventional pulsed-gradient dMRI (PG-dMRI) and OG-dMRI with oscillating frequencies from 50 to 200 Hz. Pathology at cellular and subcellular levels was evaluated using neuronal, glial, and mitochondrial markers. We found significantly higher rates of ADC increase with oscillating frequencies (Δ fADC) in the ipsilateral edema region, compared to the contralateral side, starting as early as 3 h after HI. Even in injured regions that showed no apparent change in PG-ADC or pseudo-normalized PG-ADC measurements, Δ fADC remained significantly elevated. Histopathology showed swelling of sub-cellular structures in these regions with no apparent whole-cell level change. These results suggest that OG-dMRI is sensitive to subcellular structural changes in the brain after HI and is less susceptible to pseudo-normalization than PG-dMRI.

Although the adverse effects of neonatal hypoxia associated with premature birth on the central nervous system are well known, the contribution of hypoxic damage to the peripheral nervous system (PNS) has not been addressed. We demonstrate that neonatal hypoxia results in hypomyelination and delayed axonal sorting in mice leading to electrophysiological and motor deficits that persist into adulthood. These findings support a potential role for PNS hypoxic damage in the motor impairment that results from premature birth and suggest that therapies designed to protect the PNS may provide clinical benefit.

Introduction: Perinatal asphyxia is one of the most common primary causes of mortality and morbidity among neonates. Perinatal asphyxia will result in neonatal hypoxia and tissue/organ injury. Objective: The aim of this study was to observe the Co-relation between Perinatal asphyxia with Hypoxic Ischemic Encephalopathy (PNA with HIE) and Blood sugar level. Methodology: This is a descriptive cross-sectional case study where a total of 182 neonates were admitted to the hospital with the problem of Perinatal asphyxia with Hypoxic Ischemic Encephalopathy and with some other associated problem. Result: Among the cases, 114 (62.6%) were Boys and 68 (37.45%) Girls. The mean age was 29.72 ± 78.42, Weight 2.77 ± .60, RBS 6.57 ± 7.38. Among the asphyxiated neonates blood sugar levels in arterial cord blood were significantly lower and had a negative (r=−0.195, P

Perinatal hypoxia ischemia (HI) is a significant cause of brain injury in surviving infants. Although hypothermia improves outcomes in some infants, additional therapies are needed since about 40% of infants still have a poor outcome. Acetyl-L-carnitine (ALCAR), an acetylated derivative of L-carnitine, protected against early changes in brain metabolites and mitochondrial function after HI on postnatal day (PND) 7 in a rat pup model of near-term HI injury. However, its efficacy in long-term structural and functional outcomes remains unexplored. We determined the efficacy of ALCAR therapy administered to rat pups after HI at PND 7, using both longitudinal in vivo magnetic resonance imaging and behavioral tests, in male and female rats. HI led to sex-specific behavioral impairment, with males exhibiting more global functional deficits than females. Interestingly, HI reduced the volume of the contralateral hemisphere in males only, suggesting that the brain injury is more diffuse in males than in females. Treatment with ALCAR improved both morphological and functional outcomes in both male and female rats. These results suggest that ALCAR may be a potential therapy for clinical use since the treatment attenuated the moderate injury produced under the experimental conditions used and improved the functional outcome in preclinical studies.

Objective: The objective of this pilot study was to start evaluating the efficacy and the safety (i.e., carboxyhemoglobin concentration of carbon monoxide (CO)) as a putative neuroprotective therapy in neonates. Study Design: Neonatal C57BL/6 mice were exposed to CO at a concentration of either 200 or 250 ppm for a period of 1 h. The pups were then sacrificed at 0, 10, 20, 60, 120, 180, and 240 min after exposure to either concentration of CO, and blood was collected for analysis of carboxyhemoglobin. Following the safety study, 7-day-old pups underwent a unilateral carotid ligation. After recovery, the pups were exposed to a humidified gas mixture of 8% oxygen and 92% nitrogen for 20 min in a hypoxia chamber. One hour after the hypoxia exposure, the pups were randomized to one of two groups: air (HI+A) or carbon monoxide (HI+CO). An inhaled dose of 250 ppm of CO was administered to the pups for 1 h per day for a period of 3 days. At 7 days post-injury, the pups were sacrificed and the brains analyzed for cortical and hippocampal volumes. Results: CO exposure at 200 and 250 ppm produced a peak carboxyhemoglobin concentration of 21.52 ± 1.18% and 27.55 ± 3.58%, respectively. The carboxyhemoglobin concentrations decreased rapidly, reaching control concentrations by 60 min post exposure. At 14 days of age (7 days post injury), the HI+CO (treated with 1 h per day of 250 ppm of CO for 3 days post injury) had significant preservation of the ratio of ipsilateral to contralateral cortex (median 1.07, 25% 0.97, 75% 1.23, n = 10) compared the HI+A group (p < 0.05). Conclusion: CO exposure of 250 ppm did not reach carboxyhemoglobin concentrations which would induce acute neurologic abnormalities and was effective in preserving cortical volumes following hypoxic-ischemic injury.

Objective: Optimal management of twin deliveries is controversial. We aimed to assess potential risk factors correlated to the development of hypoxia in the second twin after vaginal delivery of the first twin. Study design: This is a retrospective observational study including diamniotic twin pregnancies delivering at our Institution at 35 weeks of gestational age or more, weighing ≥1800 g. Hypoxia was defined as at least one of the following: Apgar score 10 minutes, neonatal acidosis (pH ≤7 and/or BE ≥12 mmol/L). Results: A number of 275 diamniotic twin pregnancies met the inclusion criteria and were divided within the following groups: (1) second twin not developing neonatal hypoxia (n = 265); and (2) second twin developing neonatal hypoxia (n = 10). The rate of second twins with neonatal hypoxia during the study period was 3.6% (10/275). Abnormal cardiotocography during the intertwin delivery interval, defined as ACOG category III, was significantly correlated to second twin hypoxia. Of interest, there was no significant difference in the intertwin delivery interval between the study groups. In addition, breech presentation of the second twin did not show to be a risk factor for neonatal hypoxia. None of the second twins developing neonatal hypoxia was reported to have encephalopathy (follow up of at least 24 months). At multivariate analysis, only abnormal cardiotocography was an independent risk factor for second twin hypoxia (OR 17.8, 95% CI 4.1–77.2). Conclusions: In our study, neonatal hypoxia was significantly correlated to abnormal cardiotocography, while intertwin delivery interval was not correlated to the development of this adverse neonatal outcome Objective: Optimal management of twin deliveries is controversial. We aimed to assess potential risk factors correlated to the development of hypoxia in the second twin after vaginal delivery of the first twin. Study design: This is a retrospective observational study including diamniotic twin pregnancies delivering at our Institution at 35 weeks of gestational age or more, weighing ≥1800 g. Hypoxia was defined as at least one of the following: Apgar score 10 minutes, neonatal acidosis (pH ≤7 and/or BE ≥12 mmol/L). Results: A number of 275 diamniotic twin pregnancies met the inclusion criteria and were divided within the following groups: (1) second twin not developing neonatal hypoxia (n = 265); and (2) second twin developing neonatal hypoxia (n = 10). The rate of second twins with neonatal hypoxia during the study period was 3.6% (10/275). Abnormal cardiotocography during the intertwin delivery interval, defined as ACOG category III, was significantly correlated to second twin hypoxia. Of interest, there was no significant difference in the intertwin delivery interval between the study groups. In addition, breech presentation of the second twin did not show to be a risk factor for neonatal hypoxia. None of the second twins developing neonatal hypoxia was reported to have encephalopathy (follow up of at least 24 months). At multivariate analysis, only abnormal cardiotocography was an independent risk factor for second twin hypoxia (OR 17.8, 95% CI 4.1–77.2). Conclusions: In our study, neonatal hypoxia was significantly correlated to abnormal cardiotocography, while intertwin delivery interval was not correlated to the development of this adverse neonatal outcome.

Se realizó un estudio retrospectivo parcial, longitudinal, comparativo, observacional evaluando a 2155 recién nacidos de un total de 18808, cuyo parto ocurrió entre enero de 1984 y diciembre de 1987 en el Hospital Nacional Cayetano Heredia. La incidencia de recién nacido pretérmino (RNPT) fue 4,92 % y la de bajo peso de (RNBP) 7,4%. De estos, 4,7% correspondieron a recién nacidos pretérmino de bajo peso (RNPBP). El riesgo de un nacimiento pretérmino de bajo peso, se ve influenciado por factores demográficos (paridad, grado de instrucción), antecedentes maternos (mala historia obstétrica, prematuros, toxemia e hipertensión) y complicaciones de la gestación actual. Entre las complicaciones médicas asociadas a la gestación destacaron la desnutrición, anemia e infecciones intercurrentes. Los recién nacidos pretérmino de bajo peso, se asocian significativamente a las gestaciones de mayor riesgo obstétrico, sin control prenatal a una elevada incidencia de hipoxia neonatal severa, así como a mayores tasas de morbilidad y mortalidad perinatal

Finding risk factors in pregnancy related to neonatal hypoxia is a challenging task due to the informal nature and a wide scatter of the data. In this work, we propose a methodology for sequential estimation of interestingness of association rules with two sets of criteria. The rules suggest that a strong relationship exists between the specific sets of attributes and the diagnosis. We set up a profile of the pregnant woman with a high likelihood of hypoxia of the newborn that would be beneficial to medical professionals.

Objective: To describe the value of HBO in the acute management of neonatal hypoxia (hypoxic–ischemic encephalopathy) and necrotizing enterocolitis.

We compared the efficacy of three automated brain injury detection methods, namely symmetry-integrated region growing (SIRG), hierarchical region splitting (HRS) and modified watershed segmentation (MWS) in human and animal magnetic resonance imaging (MRI) datasets for the detection of hypoxic ischemic injuries (HIIs). Diffusion weighted imaging (DWI, 1.5T) data from neonatal arterial ischemic stroke (AIS) patients, as well as T2-weighted imaging (T2WI, 11.7T, 4.7T) at seven different time-points (1, 4, 7, 10, 17, 24 and 31 days post HII) in rat-pup model of hypoxic ischemic injury were used to assess the temporal efficacy of our computational approaches. Sensitivity, specificity, and similarity were used as performance metrics based on manual ('gold standard') injury detection to quantify comparisons. When compared to the manual gold standard, automated injury location results from SIRG performed the best in 62% of the data, while 29% for HRS and 9% for MWS. Injury severity detection revealed that SIRG performed the best in 67% cases while 33% for HRS. Prior information is required by HRS and MWS, but not by SIRG. However, SIRG is sensitive to parameter-tuning, while HRS and MWS are not. Among these methods, SIRG performs the best in detecting lesion volumes; HRS is the most robust, while MWS lags behind in both respects.

Hypoxia-ischemia (HI) is a model of cerebral ischemia used to model neonatal hypoxia and to study brain damage. Interpreting the results of experiments that use HI rests partly on the assumption that only the brain suffers major damage. In this study, we demonstrate that HI also has adverse consequences on the heart. Both infarction scoring and measurements of troponin I indicate cardiac damage subsequent to HI. These results indicate that the effects of HI on the heart may confound the interpretation of experiments that have used HI to study neuroprotection or other aspects of brain damage.

BACKGROUND Hypoxic preconditioning (HPc) protects the neonatal brain in the setting of hypoxia-ischemia (HI). The mechanisms of protection may depend on activation of hypoxia inducible factor (HIF-1α). The present study sought to clarify the role of HIF-1α after HPc and HI. METHODS To induce HPc, HIF-1α knockout and wildtype mice were exposed to hypoxia at postnatal day 6. At day 7, the mice underwent HI. Brain injury was determined by histology. HIF-1α, downstream targets, and markers of cell death were measured by Western blot. RESULTS HPc protected the wildtype brain compared to wildtype without HPc, but did not protect the HIF-1α knockout brain. In wildtype, HIF-1α increased after hypoxia and after HI, but not with HPc. The HIF-1α knockout showed no change in HIF-1α after hypoxia, HI, or HPc/HI. After HI, spectrin 145/150 was higher in HIF-1α knockout, but after HPc/HI, it was higher in wildtype. LAMP2 was higher in wildtype early after HI, but not later. After HPc/HI, LAMP2 was higher in HIF-1α knockout. CONCLUSION These results indicate that HIF-1α is necessary for HPc protection in the neonatal brain, and may affect cell death after HI. Different death and repair mechanisms depend on the timing of HPc.

Purpose To investigate if frequency-dependent contrasts using oscillating gradient diffusion MRI (dMRI) can detect hypoxia–ischemia (HI) -induced neurodegeneration in the neonatal mouse hippocampus. Methods Pulsed- and oscillating-gradient dMR images (at 50, 100, and 150 Hz) were acquired from postmortem fixed brains of mice exposed to neonatal HI using the Rice-Vanucci model. MRI data were acquired at 1, 4, and 8 days following HI, and compared with histological data from the same mice for in situ histological validation of the MRI findings. Results The rate of change of apparent diffusion coefficient with gradient frequency (ΔfADC) revealed unique layer-specific contrasts in the neonatal mouse hippocampus. ΔfADC measurements were found to show a significant decrease in response to neonatal HI injury, in the pyramidal (Py) and granule (GrDG) cell layers compared with contralateral regions. The areas of reduced intensity in the ΔfADC maps corresponded to regional neurodegeneration seen with H&E and Fluoro-Jade C stainings, indicating that alterations in ΔfADC contrasts are sensitive to early microstructural changes due to HI-induced neurodegeneration in the studied regions. Conclusion The findings show that the frequency-dependence of ADC measurements with oscillating-gradient dMRI can provide a sensitive contrast to detect HI-induced neurodegeneration in neuronal layers of the neonatal mouse hippocampus. Magn Reson Med 72:829–840, 2014. © 2013 Wiley Periodicals, Inc.

It is believed that neonatal hypoxia–ischemia (HI) brain injury causes neuron loss and brain functional defects. However, the effect of HI brain injury on dendritic development of the remaining pyramidal cells of the hippocampus and the reaction of contralateral hippocampal neurons require further studies. The Morris water maze and Golgi–Cox staining were used to evaluate the learning and memory and dendritic morphology of pyramidal cells. The results of Golgi–Cox staining showed CA1 pyramidal neurons of HI injury models with fewer bifurcations and shorter dendrite length than the naive control group. The density of dendritic spines of hippocampal CA1 pyramidal neurons was significantly lower in the HI brain injury group than in controls. With respect to hippocampal function, the HI brain injury group presented cognitive deficits in the reference memory task and probe trail. In the HI group, the pyramidal cells of left hippocampus that did not experienced ischemia but did experience hypoxia had more complex dendrites and higher density of spine than the HI injury side and control. The functional implementation of injured hippocampus might depend mainly on the hypertrophy of contralateral hippocampus after HI brain injury. Corticosterone can partially prevent the hippocampal pyramidal cells from HI injury and reduce the difference of the bilateral hippocampus pyramidal cells, but there was no improvement in learning and memory. © 2013 Wiley Periodicals, Inc.

Neonatal hypoxia-ischemia (HI) affects 60% of low birth weight infants and up to 40% of preterm births. Cell death and brain injury after HI have been shown to cause long-lasting behavioral deficits. By using a battery of behavioral tests on second generation 3-week-old rodents, we found that neonatal HI is associated with behavioral outcomes in the progeny of HI-affected parents. Our results suggest an epigenetic transfer mechanism of some of the neurological symptoms associated with neonatal HI. Elucidating the transfer of brain injury to the next generation after HI calls attention to the risks associated with HI injury and the need for proper treatment to reverse these effects. Assessing the devastating extent of HI's reach serves as a cautionary tale to the risks associated with neonatal HI, and provides an incentive to create improved therapeutic measures to treat HI.

Therapeutic hypothermia in term infants with neonatal asphyxial encephalopathy has been shown to have beneficial effects in relation to neurodevelopmental outcome and survival. This paper is a critical appraisal of two studies, which compares and contrasts the methodology and findings, and incorporates a synthesis of findings with reflection on clinical practice.

Cerebro-costo-mandibular syndrome (CCMS) is a rare disorder characterized by multiple rib abnormalities, micrognathia described as Pierre-Robin sequence, and cerebral involvement. Appropriate management of respiratory distress immediately after birth is crucial to rescue these patients. A boy, having a mother with Pierre-Robin sequence and a sister with CCMS, was diagnosed prenatally with CCMS and successfully treated with ex utero intrapartum treatment (EXIT) at 36 weeks 6 days of gestation. EXIT would be an effective option for rescuing patients with prenatally diagnosed CCMS and preventing neonatal hypoxia.

Acute hypoxia at postnatal day (P) 10 is an accepted model of human neonatal hypoxia which results, among other consequences, in increased hippocampal excitability. Hypoxic–ischemic injury, which mimics stroke, has been shown to result in changes in connexins (Cxs), however, changes in Cxs have not been studied in the P10 hypoxia model. The aim of this study was to investigate changes in the hippocampal expression of three different connexins at consecutive developmental stages after acute hypoxia at P10 (10 min and 30 min after reoxygenation, P11, P14, P17, P29, and P45) as compared to sham manipulated pups. After acute hypoxia at P10, Cx30 protein levels were increased at 30 min after reoxygenation, at P11 and at P14, and then returned to control levels. Cx36 protein levels transiently decreased at P11 after acute hypoxia then returned to control levels. Cx43 protein levels did not change at any of the time points. Although changes in mRNA expression were observed during development for Cx30 only, acute hypoxia did not result in changes in mRNA expression of all these Cxs when compared to age matched controls suggesting that acute hypoxia induced posttranslational changes in protein expression.

Although recent studies have documented compensatory generation of neurons in adult brains in response to various insults, a noninjurious short episode of hypoxia in rat neonates has been shown to trigger neurogenesis within the ensuing weeks, without apparent brain lesions. Very little is known of the long-term consequences. We therefore investigated the effects of such a conditioning-like hypoxia (100% N(2), 5 min) on the brain and the cognitive outcomes of rats at 40 to 100 days of age. Control and posthypoxic rats developed similar learning capacities over postnatal days 14 to 18, but hypoxia was associated with enhanced scores in a test used to evaluate memory retrieval between 40 and 100 days. A striking sexual dimorphism was observed, with an earlier functional gain observed in female (40 days) compared with male (100 days) rats; gains were associated with matching structural changes in areas involved in cognition, including the hippocampus and frontal cortex. Therefore, it is proposed that brief neonatal hypoxia may exert long-term beneficial effects through neurogenesis stimulation.

Neonatal hypoxic ischemic injury (HII) is a devastating brain disease for which hypothermia is currently the only approved treatment. As new therapeutic interventions emerge there is a significant need for noninvasive objective quantification of the spatiotemporal lesion dynamics combined with precise information about lesion constituents (ischemic core and penumbra). These metrics are important for deciding treatment parameters (type, time, site, and dose) and for monitoring injury-therapy interactions. Such information provided ‘on-line’ in a timely fashion to the clinician could revolutionize clinical management. Like other spatiotemporal biological processes, video bioinformatics can assist objective monitoring of injury–therapy interactions. We have been studying the efficacy of various potential treatments in translational (rodent) HII models using magnetic resonance imaging (MRI). We have developed a novel computational tool, hierarchical region splitting (HRS) to rapidly identify ischemic lesion metrics. HRS detects similar lesion volumes compared to manual detection methods and is fast, robust, and reliable compared to other computational methods. HRS also provides additional information about the location, size, and evolution of the core and penumbra, which are difficult to ascertain with manual methods. This chapter summarizes the ability of HRS to identify lesion dynamics and ischemic core-penumbra evolution following neonatal HII. In addition, we demonstrate that HRS provides information about lesion dynamics following different therapies (e.g., hypothermia, stem cell implantation). Our findings show that computational analysis of MR images using HRS provides novel quantitative approaches that can be applied to clinical and translational stroke research using data mining of standard experimental and clinical MRI data.

Hypoxia is the most common cause of neonatal seizures and can lead to epilepsy, but the epileptogenic mechanisms are not yet understood. We have previously shown that hypoxia-induced seizures in the neonatal rat result in acutely decreased amplitudes and frequency of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in hippocampal CA1 pyramidal neurons. In the current study, we asked whether such changes persist for several days following hypoxia-induced seizures. Similar to the acute findings, we observed decreased frequency and amplitudes of sIPSCs and decreased mIPSC amplitudes in CA1 pyramidal neurons at 3–5 days after hypoxia. However, in contrast to the acute findings, we observed no differences between hypoxia-treated and control groups in mIPSC frequency. Additionally, by 7 days after hypoxia, sIPSC amplitudes in the hypoxia group had recovered to control levels, but sIPSC frequency remained decreased. These data indicate that the persistently decreased sIPSC frequency result from decreased firing of presynaptic inhibitory interneurons, with only transient possible changes in postsynaptic responses to GABA release.

A participação de marcadores bioquímicos na avaliação de quadros de asfixia neonatal é cada vez mais relevante. A proteína S100B é de particular importância neste campo. O objetivo deste estudo foi procurar destacar a importância da proteína S100B na avaliação de recém-nascidos a termo com quadro de encefalopatia hipóxico-isquêmica, assim como correlacionar com outras substâncias que também participam do processo isquêmico. Foram analisados 21 casos de recém nascidos a termo que desenvolveram encefalopatia hipóxico-isquêmica no período de setembro de 2003 a outubro de 2004. Realizadas coletas no 1º e 4º dia de vida e dosadas, por método imunocitoquímico, a proteína S100B e o lactato. Observouse correlação positiva entre as duas substâncias, assim como quando comparadas entre si nas suas respectivas dosagens, obteve-se significância estatística. Biochemical markers have played an increasingly relevant role in the assessment of neonatal asphyxia. The S100B protein is particularly important in re s e a rch conducted in this field. The purpose of this study was to underline the importance of the S100B protein in the assessment of term newborn infants with hypoxic-ischemic encephalopathy, as well as to relate it to other substances also involved in the ischemic p rocess. An assessment was made from September 2003 to October 2004 of 21 term newborn infants who developed hypoxic-ischemic encephalopathy. Samples were collected on the 1st and 4th day of life and S100B p rotein and lactate concentrations were calculated using the immune cytochemical method. A positive relationship was found between the two substances. Additionally, a comparison between the two substances showed a statistically significant correlation.

Permanent damage to white matter tracts, comprising axons and myelinating oligodendrocytes, is an important component of brain injuries of the newborn that cause cerebral palsy and cognitive disabilities, as well as multiple sclerosis in adults. However, regulatory factors relevant in human developmental myelin disorders and in myelin regeneration are unclear. We found that AXIN2 was expressed in immature oligodendrocyte progenitor cells (OLPs) in white matter lesions of human newborns with neonatal hypoxic-ischemic and gliotic brain damage, as well as in active multiple sclerosis lesions in adults. Axin2 is a target of Wnt transcriptional activation that negatively feeds back on the pathway, promoting β-catenin degradation. We found that Axin2 function was essential for normal kinetics of remyelination. The small molecule inhibitor XAV939, which targets the enzymatic activity of tankyrase, acted to stabilize Axin2 levels in OLPs from brain and spinal cord and accelerated their differentiation and myelination after hypoxic and demyelinating injury. Together, these findings indicate that Axin2 is an essential regulator of remyelination and that it might serve as a pharmacological checkpoint in this process.

WOS:000346149200005 PubMed: 25491683 Background. Neonatal hypoxic-ischemic (HI) injury has been considered to have acute and long term deleterious effects on many tissues, including the peripheral nerve. Objectives. In this study, the effects of a tumor necrosis factor-alpha (TNF-alpha) inhibitor (etanercept) on peripheral nerve damage and the ultrastructure of the sciatic nerve and gastrocnemius muscle in rats exposed to HI during the neonatal period were examined. Material and Methods. In this study, 45 seven-day-old rats were used and they were divided into three groups. The right carotid arteries of the rats in the saline and etanercept groups were ligated and put in a hypoxia chamber containing 8% oxygen for two hours. Just after hypoxia, the etanercept group was given 10 mg/kg etanercept, but the saline group had only saline intraperitoneally. The sham group rats' carotid arteries were not ligated or put in hypoxia. The amplitude, area and latency of sciatic nerve compound motor action potential (CMAP), which mainly reflects axonopathy and myelinopathy, were measured using standard techniques in the seventeenth week following the HI. Sciatic nerve and gastrocnemius muscle were evaluated with a transmission electron microscope, and grading for myelin sheath damage was done to all groups. Results. Neuropathy was seen in rats after HI. While treatment with etanercept showed a protective effect for the axons of sciatic nerve, demyelination could not be recovered with etanercept. Conclusions. This study is the first in literature to show a partial interruption of the signal through the peripheral nerve fibers caused by axonal and myelin dysfunction continuation in rats exposed to HI after birth, in the 17th week