Search

Perinatal brain damage is still one of the leading contributors to perinatal death and postnatal disability worldwide. However, the term perinatal brain damage encompasses very different aetiological entities that result in an insult to the developing brain and does not differentiate between the onset, cause and severity of this insult. Hypoxic-ischemic encephalopathy (HIE), intraventricular haemorrhage, periventricular leukomalacia and perinatal stroke are often listed as the major aetiologies of perinatal brain damage. They differ by type and timing of injury, neuropathological and imaging findings and their clinical picture. Along the timeline of neurodevelopment in utero, there appears to be a specific "window of vulnerability" for each type of injury, but clinical overlap does exist. In the past, peripartum acute hypoxia was believed to be the major, if not the only, cause of perinatal brain damage, but intrauterine inflammation, prematurity, chronic hypoxia/growth retardation and genetic abnormalities appear to be at least equally important contributors. [ABSTRACT FROM AUTHOR]

To assess the maturational status of the brainstem auditory pathway in babies with apnoea of prematurity (AOP) at 33–34 weeks of postmenstrual age (PMA), an important time landmark at which AOP is resolved in most cases. Compare brainstem auditory maturation between very preterm babies with AOP and those without AOP (non-AOP) at the same PMA 33–34 weeks to define differences. The AOP group showed significantly longer latencies of waves III and V latency than the non-AOP group (p < 0.05 and 0.01). The I-V interval in the AOP group was significantly longer than in the non-AOP group (p < 0.001). The same was true for the I-III and III-V intervals (p < 0.001 and 0.05). Wave III amplitude was significantly smaller (p < 0.05), and wave V amplitude was moderately smaller than in the non-AOP. At PMA 33 weeks, waves III and V latencies and all intervals in the AOP group were significantly longer than in the non-AOP group (p < 0.05–0.001). At PMA 34 weeks, these wave latencies and intervals in the AOP group were still significantly longer than in the non-AOP group (p < 0.05–0.01). Wave III amplitude in the AOP group was significantly smaller at both PMA 33 and 34 weeks (p < 0.05 and 0.05). Brainstem auditory maturation in AOP babies is delayed at PMA 33 weeks, and remains delayed at PMA 34 weeks. These findings highlight the importance of monitoring and adequate intervention strategies during PMA 33–34 weeks in AOP babies. • Brainstem auditory maturation in AOP babies was assessed at PMA 33–34 weeks. • AOP babies manifested significantly prolonged BAER wave latencies and interpeak intervals. • Brainstem auditory maturation in AOP babies is delayed at both PMA 33 and 34 weeks. • Monitoring and adequate intervention strategy are required at this important time in AOP babies. [ABSTRACT FROM AUTHOR]

The sense of sight plays a very important role in the life of every individual, since we receive most of the information from the environment with the help of sight. Visually impaired children have difficulty receiving information from the world around them. Lack of visual experience can negatively affect their development. Timely examinations and assessments will indicate the occurrence of various neurological disorders in children, if any are present. A very common cause of neurological disorders is perinatal brain damage. Children with perinatal brain damage often have difficulties in visual functioning and it is therefore very important to assess functional vision in these children. If there are any neurodevelopmental disorders in the child, it is important to start vision rehabilitation as soon as possible, in order to effectively influence the improvement of visual functions.

To examine postnatal changes in the impaired brainstem auditory pathway in term infants after perinatal hypoxia-ischemia (HI). Brainstem auditory evoked response (BAER) was studied at 2–4 months of age in term infants who suffered perinatal HI. The BAER data obtained at various click rates in these infants were compared with those in age-matched normal term controls to detect any abnormalities. The infants after HI showed a slight elevation in BAER threshold. Four (9.8%) infants had threshold elevation. At 21/s clicks, there was a slight decrease in wave I latency, and a slight increase in wave III and V latencies. However, the I–V and I–III intervals in these infants were significantly increased (p <.05 and.05), whereas III–V interval was slightly increased. At higher click rates of 51 and 91/s, all BAER variables showed similar changes, with only small variations. An abnormal increase in the I–V and/or I–III intervals was seen in 4 (9.8%) infants, who were not associated with BAER threshold elevation. At 2–4 months of age, around 20% of the infants after perinatal HI showed a moderate degree of either peripheral or central impairment of the brainstem auditor pathway. Monitoring postnatal changes could provide valuable information for postnatal care of infants after perinatal HI. [ABSTRACT FROM AUTHOR]

Recent studies showed that neonatal necrotizing enterocolitis (NEC) adversely affects the brainstem auditory pathway in babies born at 30–40 week gestation. We compared the functional status of the pathway between babies born below 30 week gestation with NEC and those without NEC for any differences to understand whether NEC also affects the pathway in babies born at a smaller gestation. Brainstem auditory evoked response was studied at term in NEC babies born below 30 week gestation. The data obtained were compared with age-matched non-NEC babies for any abnormalities, and then compared with previously reported NEC babies born at 30–34 week gestation for any differences. Although the latencies of waves I and III did not differ significantly between NEC and non-NEC babies, wave V latency in NEC babies was longer than in non-NEC babies at all click rates used. In particular, I–V interpeak interval, reflecting brainstem conduction time, in NEC babies was significant longer than in non-NEC babies. Wave V amplitude and the V/I amplitude ratios in NEC babies was smaller than in non-NEC babies at some click rates. The I–V interval in our NEC babies born below 30 week gestation was longer than in previously reported NEC babies born at 30–34 week gestation at all click rates. NEC babies born below 30 week gestation are associated with delayed brainstem conduction time. Functional status of the brainstem auditory pathway in NEC babies born below 30 week gestation is less favorable than that in those with greater gestation. [ABSTRACT FROM AUTHOR]

Abstract Background Preterm newborns are at high risk of developing neurodevelopmental deficits caused by neuroinflammation leading to perinatal brain injury. Human Wharton’s jelly mesenchymal stem cells (hWJ-MSC) derived from the umbilical cord have been suggested to reduce neuroinflammation, in part through the release of extracellular vesicle-like exosomes. Here, we studied whether exosomes derived from hWJ-MSC have anti-inflammatory effects on microglia-mediated neuroinflammation in perinatal brain injury. Methods Using ultracentrifugation, we isolated exosomes from hWJ-MSC culture supernatants. In an in vitro model of neuroinflammation, we stimulated immortalized BV-2 microglia and primary mixed glial cells with lipopolysaccharide (LPS) in the presence or absence of exosomes. In vivo, we introduced brain damage in 3-day-old rat pups and treated them intranasally with hWJ-MSC-derived exosomes. Results hWJ-MSC-derived exosomes dampened the LPS-induced expression of inflammation-related genes by BV-2 microglia and primary mixed glial cells. The secretion of pro-inflammatory cytokines by LPS-stimulated primary mixed glial was inhibited by exosomes as well. Exosomes interfered within the Toll-like receptor 4 signaling of BV-2 microglia, as they prevented the degradation of the NFκB inhibitor IκBα and the phosphorylation of molecules of the mitogen-activated protein kinase family in response to LPS stimulation. Finally, intranasally administered exosomes reached the brain and reduced microglia-mediated neuroinflammation in rats with perinatal brain injury. Conclusions Our data suggest that the administration of hWJ-MSC-derived exosomes represents a promising therapy to prevent and treat perinatal brain injury.

Prenatal and perinatal risk factors for perinatal brain damage frequently produce brain injuries in preterm and term infants. The early diagnosis and treatment of these infants, in the period of higher brain plasticity, may prevent the neurological and cognitive sequels that accompany these lesions. The Neurodevelopmental Research Unit at the Institute of Neurobiology of the National Autonomous University of Mexico has taken this endeavor. A multidisciplinary approach is followed. Pediatric, neurologic and rehabilitation clinical studies, MRI, EEG, visual and auditory evoked responses, and Bayley II evaluations are carried out initially. Infants are followed up to 8 years, with periodic appointments for evaluation and treatment. Katona's neurohabilitation method is used for initial diagnosis and treatment. Selective visual and auditory attention are explored from 3 months of age. This method was created in the Unit and, if deficiencies are observed, the method also describes the treatment to avoid subsequent alterations of these processes. Deficiencies in the acquisition of language are evaluated from 4 months of age, implementing treatment through instructions to parents on how they should teach their children to speak. This method has also been developed in the Unit and is in its validation process. In the MRI, we pay special attention to subtle and diffuse patterns, due to the high frequency with which they appear in contemporary cohorts at a national and international level. More than 80% of these infants showed abnormal MRI findings that should be taken into consideration. The outcome of children at 8 years old showed that 78%, 76% and 78% of extremely preterm, very preterm and late preterm, respectively, had a normal neurodevelopment. In term infants, only 69% had a normal neurodevelopment; in this group, the majority of infants had very severe brain lesions. Conclusions: It is necessary to evaluate, at an early age, all newborns with prenatal and perinatal risk factors for brain damage. Special attention should be payed to all premature newborns and those newborns who have been discharged from the intensive care unit.

Midkine (MK) is a small secreted heparin-binding protein highly expressed during embryonic/fetal development which, through interactions with multiple cell surface receptors promotes growth through effects on cell proliferation, migration, and differentiation. MK is upregulated in the adult central nervous system (CNS) after multiple types of experimental injury and has neuroprotective and neuroregenerative properties. The potential for MK as a therapy for developmental brain injury is largely unknown. This review discusses what is known of MK's expression and actions in the developing brain, areas for future research, and the potential for using MK as a therapeutic agent to ameliorate the effects of brain damage caused by insults such as birth-related hypoxia and inflammation.

Evidence for umbilical cord blood (UCB) cell therapies as a potential intervention for neurological diseases is emerging. To date, most existing trials worked with allogenic cells, as the collection of autologous UCB from high-risk patients is challenging. In obstetric emergencies the collection cannot be planned. In preterm infants, late cord clamping and anatomic conditions may reduce the availability. The aim of the present study was to assess the feasibility of UCB collection in neonates at increased risk of brain damage. Infants from four high-risk groups were included: newborns with perinatal hypoxemia, gestational age (GA) ≤30 + 0 weeks and/or birthweight <1,500 g, intrauterine growth restriction (IUGR), or monochorionic twins with twin-to-twin transfusion syndrome (TTTS). Feasibility of collection, quantity and quality of obtained UCB [total nucleated cell count (TNC), volume, sterility, and cell viability], and neonatal outcome were assessed. UCB collection was successful in 141 of 177 enrolled patients (hypoxemia n = 10; GA ≤30 + 0 weeks n = 54; IUGR n = 71; TTTS n = 6). Twenty-six cases were missed. The amount of missed cases per month declined over the time. Volume of collected UCB ranged widely (median: 24.5 ml, range: 5.0–102 ml) and contained a median of 0.77 × 108 TNC (range: 0.01–13.0 × 108). TNC and UCB volume correlated significantly with GA. A total of 10.7% (19/177) of included neonates developed brain lesions. To conclude, collection of UCB in neonates at high risk of brain damage is feasible with a multidisciplinary approach and intensive training. High prevalence of brain damage makes UCB collection worthwhile. Collected autologous UCB from mature neonates harbors a sufficient cell count for potential therapy. However, quality and quantity of obtained UCB are critical for potential therapy in preterm infants. Therefore, for extremely preterm infants alternative cell sources such as UCB tissue should be investigated for autologous treatment options because of the low yield of UCB. [ABSTRACT FROM AUTHOR]

Midkine (MK) is a small secreted heparin-binding protein highly expressed during embryonic/fetal development which, through interactions with multiple cell surface receptors promotes growth through effects on cell proliferation, migration, and differentiation. MK is upregulated in the adult central nervous system (CNS) after multiple types of experimental injury and has neuroprotective and neuroregenerative properties. The potential for MK as a therapy for developmental brain injury is largely unknown. This review discusses what is known of MK's expression and actions in the developing brain, areas for future research, and the potential for using MK as a therapeutic agent to ameliorate the effects of brain damage caused by insults such as birth-related hypoxia and inflammation. [ABSTRACT FROM AUTHOR]

Aims: Magnesium sulfate has neuroprotective effects in preterm infants. Whether other antepartum treatments interfere with the neuroprotective actions is not well known. This study aims to explore the impacts of antenatal administration of Magnesium sulfate or beta‐2 adrenergic agonists as tocolytic agents on the developing brain in premature infants. Methods: This is a retrospective cohort study in four tertiary perinatal centers in Japan. We collected data of pregnant women and infants born between 28 and 36 weeks for tocolytic agents, gestational age, sex, antenatal corticosteroid, fetal growth restriction, pathological chorioamnionitis, low umbilical arterial pH values (<7.1), multiple pregnancy, mode of delivery and institutions after excluding clinical chorioamnionitis, non‐reassuring fetal status or major anomalies. Tocolytic agents were categorized into four groups: no‐tocolysis, magnesium sulfate, beta‐2 adrenergic agonists and the combination of them. We conducted multiple comparisons with multivariate analyses using generalized linear regression models to compare the prevalence of a poor perinatal outcome defined as infant's death, brain damage, particularly cerebral palsy and developmental delay. Results: Among 1083 infants, 39% were no‐tocolysis, 47% were magnesium sulfate, 41% were beta‐2 adrenergic agonists and 27% were combination group, including the duplication. The incidence of poor perinatal outcome was decreased by magnesium sulfate (OR 0.27, 95% CI 0.10–0.72), but not changed significantly by beta‐2 adrenergic agonists (OR 1.28, 95% CI 0.63–2.59) or the combination group (OR 2.24, 95% CI 0.67–7.54), compared with the no‐tocolysis. Conclusion: The combination therapy for tocolysis with beta‐2 adrenergic agonists diminished the magnesium sulfate neuroprotective action after adjusting for covariables. [ABSTRACT FROM AUTHOR]

Background: Following birth asphyxia there is a robust inflammatory response. NLRP3 is a receptor of the innate immune system. Upon activation, NLRP3 forms an inflammasome together with ASC and procaspase-1 to mediate release of IL-1β and IL-18. NLRP3 has previously been shown to be upregulated following neonatal hypoxic-ischemic (HI) brain injury in mice, but with no early effect on brain injury. Objective: We aimed to evaluate if deficiency of NLRP3 or ASC protects against neonatal HI brain damage 7 days after hypoxia-ischemia. Methods: C57BL/6J, NLRP3–/–, and ASC–/– mice were subjected to unilateral common carotid artery ligation followed by hypoxia at P9. Brain infarction, apoptosis, and microglial response were evaluated, as well as total RNA sequencing and examination of plasma levels of systemic proinflammatory cytokines. Results: NLRP3–/– mice showed significantly increased brain infarction volumes compared to wild-type (Wt) mice, while ASC–/– mice showed reduced brain infarction volumes after neonatal hypoxia-ischemia. The amount of activated microglia was increased in NLRP3–/– mice, while decreased in ASC–/– mice compared to Wt mice. Total RNA sequencing showed an impaired inflammatory transcriptional response in the hippocampus of NLRP3–/– mice. Plasma levels of IL-1β and IL-18 were not affected, but TNF was lower in NLRP3–/– and ASC–/– mice compared to Wt mice. Conclusion: ASC deficiency is neuroprotective in neonatal HI brain damage in mice, while NLRP3 deficiency increases brain damage. [ABSTRACT FROM AUTHOR]

Vision is one of the dominant senses. Humans perceive up to 80% of all impressions from our environment by means of our sight. Vision plays central role in child's ability to gather information about the world and in the way child learns about the world. Visual impairment can affect all areas of child's development and can have long-term impact on child's life. Vision or sight, as a sense, has significant impact on child's general development. Timely recognition of the risks that can lead to visual impairments and appropriate intervention can decrease impact of visual impairment on one's life and can improve quality of life. Current researches suggest that high-risk children are more likely to develop visual impairments. Researches also suggest that children in this category need to undergo assessments starting from the birth in order to determine how they use their vision in every day activities. Functional vision assessment is an assessment of how a child uses the vision in every day life, i.e. child's abilities in visual activities. Timely assessment of children with perinatal brain demage enables early detection of potential visual impairments. Early detection of visual difficulties provides possibility for creating adequate methods of habilitation based on neuroplasticity in infants and children. Main objective of this paperis to point out the connection between visual impairments and child's general development as well as importance of early detection of possible visual impairments in high-risk children so appropriate habilitation programmes could be conducted as early as possible. [ABSTRACT FROM AUTHOR]

To examine postnatal functional status of the brainstem auditory pathway in late preterm infants and detect any postnatal auditory abnormality. Thirty preterm infants born at 33–36 weeks gestation were studied three months after term. None had major perinatal and postnatal complications to minimize confounding effects. Brainstem auditory evoked responses were recorded with 21–91/s clicks. Compared with postnatal age-matched normal term infants, the late preterm infants did not manifest any major abnormalities in brainstem auditory evoked responses at conventionally used 21/s clicks. At higher click rates, however, the late preterm infants manifested a moderate prolongation in BAER wave V latency. All interpeak intervals tended to be prolonged at higher click rates. The I-V interval was significantly prolonged at 51/s and particularly at 91/s clicks. Both the I-III and III-V intervals were significantly prolonged at 91/s. The late preterm infants also manifested reduced amplitudes of BAER waves III and V at most click rates. The central components of the brainstem auditory evoked responses were abnormal at higher click rates three months after term in the late preterm infants. Postnatal brainstem auditory function is suboptimal in late preterm infants without major complications. This suboptimal brainstem auditory function may not be clearly shown at term or an earlier stage, but can be shown later. Late preterm infants, although they may not have major complications, should be followed for later auditory development, providing valuable information for improving postnatal care. [ABSTRACT FROM AUTHOR]

Copyright of Rigakuryoho Kagaku is the property of International Press Editing Center Incorporation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This review covers our current knowledge of the causes of perinatal brain injury leading to cerebral palsy‐like outcomes, and argues that much of this brain damage is preventable. We review the experimental evidence that there are treatments that can be safely administered to women in late pregnancy that decrease the likelihood and extent of perinatal brain damage that occurs because of acute and severe hypoxia that arises during some births, and the additional impact of chronic fetal hypoxia, infection, inflammation, growth restriction and preterm birth. We discuss the types of interventions required to ameliorate or even prevent apoptotic and necrotic cell death, and the vulnerability of all the major cell types in the brain (neurons, astrocytes, oligodendrocytes, microglia, cerebral vasculature) to hypoxia/ischaemia, and whether a pan‐protective treatment given to the mother before birth is a realistic prospect. Preventing perinatal brain damage. [ABSTRACT FROM AUTHOR]

Introduction: Extremely premature babies, particularly those who have neonatal bronchopulmonary dysplasia, are at risk of brain damage and neurodevelopmental impairment. This study aimed to examine functional status of the brainstem auditory pathway in extremely premature babies and assess the impact of bronchopulmonary dysplasia on function.Material and Methods: Brainstem auditory evoked response was studied at term in babies born at ≤27 weeks of gestation with or without neonatal bronchopulmonary dysplasia. The normal controls were term babies without perinatal problems.Results: Compared with the normal controls, the extremely premature babies showed an elevated response threshold, increased latencies of waves I, III and particularly V. They also showed significantly increased I-V and III-V intervals. The amplitudes of waves I and V were moderately reduced. These abnormalities were clearly more significant in those with bronchopulmonary dysplasia than those without bronchopulmonary dysplasia. A direct comparison between the two groups of extremely premature babies revealed that wave V latency, and I-V and particularly III-V intervals were significantly longer in the babies with bronchopulmonary dysplasia than those without bronchopulmonary dysplasia.Conclusions: Extremely premature babies have functional impairment of the brainstem auditory pathway. The impairment is clearly more significant in those with bronchopulmonary dysplasia than those without bronchopulmonary dysplasia. Neonatal bronchopulmonary dysplasia and associated unfavorable conditions are major contributors to brainstem auditory impairment in extremely premature babies. [ABSTRACT FROM AUTHOR]

Aim The creatine phosphokinase (CPK) level is believed to increase in neonatal peripheral blood after tissue damage, including damage from perinatal hypoxia. However, it is not clear whether it is truly a reliable marker for fetal hypoxia. We investigated the chronological changes in neonatal CPK and the reliability of CPK as a marker for fetal hypoxia. Methods Sixty term neonates admitted to the neonatal intensive care unit at Tokyo Women's Medical University Medical Center East from April 2009 to April 2010 were enrolled in this study. We evaluated whether asphyxia and fetal heart rate (FHR) abnormality could predict the neonatal CPK level by using receiver-operator curve analysis. We also compared umbilical cord blood pH levels with neonatal CPK levels. In addition, we investigated factors that influence neonatal CPK in non-asphyxia cases. Results The median value of CPK peaked on day 1. There were no significant differences in CPK levels regardless of the presence of asphyxia or FHR abnormality. Non-asphyxiated neonates with older gestational ages and amniotic fluid abnormalities had significantly higher levels of CPK. Conclusion Our results indicate that the neonatal CPK level is not an appropriate marker for retrospectively predicting either asphyxia or FHR abnormality. There are influencing factors other than asphyxia that increase neonatal CPK. Therefore, one should be careful when making a diagnosis of perinatal hypoxia based solely on increased levels of neonatal CPK after birth. [ABSTRACT FROM AUTHOR]

Aim: To examine brainstem auditory function at 36-37weeks of postconceptional age in preterm infants who are diagnosed to have neonatal chronic lung disease (CLD).Study Design: Preterm infants, born at 31 and less weeks of gestation, were studied at 36-37weeks of postconceptional age when they were diagnosed to have neonatal CLD. Brainstem auditory evoked response (BAER) was recorded and analyzed at different click rates.Results: Compared with healthy controls at the same postconceptional age, the CLD infants showed a slightly increase in BAER wave V latency. However, the I-V, and III-V interpeak intervals in the CLD infants were significantly increased. The III-V/I-III interval ratio was also significantly increased. The amplitudes of BAER waves III and V in the CLD infants tended to be reduced. These BAER findings were similar at all 21, 51 and 91/s clicks, although the abnormalities tended to be more significant at higher than at low click rates.Conclusion: At 36-37weeks of postconceptional age, BAER was abnormal in preterm infants who were diagnosed to have neonatal CLD. This suggests that at time when the diagnosis of CLD is made there is functional impairment, reflecting poor myelination, in the brainstem auditory pathway in preterm infants with neonatal CLD. [ABSTRACT FROM AUTHOR]

Objective To examine brainstem auditory electrophysiology in high-risk babies born at 28–32 week gestation by analysing the amplitudes of wave components in maximum length sequence brainstem auditory evoked response (MLS BAER). Methods 94 preterm babies, ranging in gestation 28–32 weeks, with perinatal problems (high-risk) were recruited. The amplitudes of MLS BAER wave components were studied at term age (37–42 weeks postconceptional age). Results Compared with normal term controls, the amplitude in the high-risk preterm babies was significantly smaller at the highest click rate 910/s for wave I ( p < 0.01), at all 91–910/s for wave III (all p < 0.01) and at 455 and 910/s ( p < 0.05 and 0.01) for wave V. Compared with age-matched low-risk preterm controls, the amplitude was significantly smaller at 455 and 910/s for wave I ( p < 0.05 and 0.05), 91–910/s for wave III ( p < 0.05–0.001), and 227–910/s ( p < 0.05 and 0.01) for wave V. No differences in the V/I and V/III amplitude ratios were found between the high-risk preterm babies and the controls. Conclusions The amplitudes of MLS BAER wave components, mainly more central components, were reduced in the high-risk preterm babies born at 28–32 week gestation. Electrophysiological activity of the brainstem auditory neuron in such babies is depressed, mainly attributed to or related to the associated perinatal problems. [ABSTRACT FROM AUTHOR]

Environmental enrichment (EE) is considered an efficient neuroprotector against neonatal hypoxia-ischemia (HI). Nevertheless, the mechanisms involved are not yet clear. In this context, the aim of this study was to investigate the effects of neonatal HI and environmental stimulation in the hippocampus of rats at 3 different time points (PND 8, 22 and 60), evaluating some aspects of BBB structure and function. Seven-day-old Wistar rats were divided into four groups: a control group maintained in a standard environment (CTSE), a control group maintained in an enrichment environment (CTEE), an HI group maintained in a standard environment (HISE) and an HI group maintained in an enrichment environment (HIEE). At the 7th postnatal day (PND), rats were submitted to the Levine-Rice model of neonatal HI. This method consists of permanent occlusion of the right common carotid artery with subsequent exposure to hypoxia. Rats from CTEE and HIEE were stimulated with environmental enrichment. The EE protocol started 24 h after HI, in which pup rats with their dams were stimulated in a maintained EE (PND 8–22). Subsequently, animals were submitted to daily EE (1 h/day, PND 23–60). The expression of some proteins involved in BBB structure (β-catenin, occludin, connexin-43, aquaporin-4, glut-1 and GFAP) were quantified by western blotting in the hippocampi of rats in three periods, at PND 8, 22 and 60. The BBB permeability and integrity was assessed by Evans blue staining and the immunohistochemistry for GFAP in the CA1 region of the hippocampus were also performed. The results showed an HI-induced decreased occludin expression at PND 22 and low levels of occludin, β-catenin and GFAP at PND 60 in the hippocampus of the hypoxic-ischemic rats. Interestingly, in young and adult rats, EE reversed these effects. Evans blue extravasation into the brain parenchyma confirmed the BBB dysfunction brought on by HI. No differences were observed at PND 8, probably due to the immaturity of the BBB at this age. The present study makes an important contribution to understanding the mechanism of the hypoxic-ischemic brain damage and also to presents, for the first time, the recovery of BBB dysfunction as a possible pathway for the protective effect of EE. [ABSTRACT FROM AUTHOR]

Copyright of Panamerican Journal of Neuropsychology / Cuadernos de Neuropsicología is the property of Cuadernos de Neuropsicologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective The neurohabilitation treatment has been shown to be a successful method for decreasing the sequelae of perinatal brain damage (PBD) in Hungarian population. The goal of this pilot trial was to introduce this procedure by describing the results of its application in infants with PBD as demonstrated by clinical, developmental and MRI studies. As this procedure has proved to be useful, according the declaration of Helsinki, no control clinical trial was permitted. Participants Infants younger than 2 months of corrected age (CA) with prenatal and/or perinatal risk factors for brain damage. Two groups were considered. One group was treated using the “neurohabilitation” method ( n = 20), and the other was not treated ( n = 13) because treatment was voluntarily discontinued after the initial evaluation. Evaluations were carried out prior to 2 months of CA and at 6–8 years of age. All children showed abnormal clinical and MRI characteristics in the first study. Results The treated group had a higher percentage (90%) of children with normal outcome than did the non-treated group (38%; OR = 2.37, CI 95% = 1.2–4.7; p < 0.005). In this latter group, only one out of five (20%) children born at or before 34 weeks of gestational age had a normal outcome. In contrast, eight out of nine treated preterm infants had normal outcomes (8/9 = 89%, OR = 4.45, CI 95% = 0.7–26; p = 0.017). Conclusions This pilot trial confirms previous studies suggesting that Neurohabilitation decreases the neurological and cognitive sequelae of preterm and at-term infants with PBD. [ABSTRACT FROM AUTHOR]

Purpose: To review historical scientific background and new perspective on the pathology of perinatal brain damage. The relationship between birth asphyxia and subsequent cerebral palsy has been extensively investigated. The role of new and promising clinical markers of oxidative stress (OS) is presented. Methods: Electronic search of PubMed-Medline/EMBASE database has been performed. Laboratory and clinical data involving case series from the research group are reported. Results: The neuropathology of birth asphyxia and subsequent perinatal brain damage as well as the role of electronic fetal monitoring are reported following a review of the medical literature. Conclusions: This review focuses on OS mechanisms underlying the neonatal brain damage and provides different perspective on the most reliable OS markers during the perinatal period. In particular, prior research work on neurodevelopmental diseases, such as Rett syndrome, suggests the measurement of oxidized fatty acid molecules (i.e., F-Neuroprostanes and F-Dihomo-Isoprostanes) closely related to brain white and gray matter oxidative damage. [ABSTRACT FROM AUTHOR]

Highlights: [•] High-risk very preterm infants showed significantly abnormalities in maximum length sequence brainstem auditory evoked response, particularly the components that reflect central neural function. [•] The abnormalities were more significant when compared with normal term infants than with low-risk very preterm infants. [•] The impaired neural conduction along the auditory brainstem, mainly the more central regions, in high-risk very preterm infants is mainly attributed to the associated perinatal problems and partly related to very preterm birth. [ABSTRACT FROM AUTHOR]

Epidemiological studies have shown a strong association between perinatal infection/inflammation and brain damage in preterm infants and/or neurological handicap in survivors. Experimental studies have shown a causal effect of infection/inflammation on perinatal brain damage. Infection including inflammatory factors can disrupt programmes of brain development and, in particular, induce death and/or blockade of oligodendrocyte maturation, leading to myelin defects. Alternatively, in the so-called multiple-hit hypothesis, infection/inflammation can act as predisposing factors, making the brain more susceptible to a second stress (sensitization process), such as hypoxic-ischaemic or excitotoxic insults. Epidemiological data also suggest that perinatal exposure to inflammatory factors could predispose to long-term diseases including psychiatric disorders. [ABSTRACT FROM AUTHOR]

We investigated effects of activation of TRESK channels by selective activator cloxyquin on excitotoxic-induced brain injury and neuroinflammation involving brain mast cells and inflammatory cytokines in neonatal rats. Three different doses of cloxyquin (0.2, 1 and 5 mg/kg) were studied in ibotenate-induced perinatal brain injury (PBI) in P5 rat-pups. Cerebral lesions and mast cells in coronal brain sections were evaluated. Concentrations of activin A, IL-1β, IL-6 and IL-10 in brain homogenates were measured using ELISA. Cloxyquin dose-dependently exerted protective effects against excitotoxic-induced neonatal brain injury and neuroinflammation. TRESK channels may be a promising new target for the treatment of PBIs. Ibotenate leads to white matter cysts and reduced gray and white matter thickness. Additionally, ibotenate induces degranulation of brain mast cells and increases the concentrations of pro-inflammatory cytokines IL-1β and IL-6 in the brain tissue while it decreases IL-10 level, thus leading to the neuroinflammation. However, cloxyquin dose-dependently prevents excitotoxic-induced neonatal brain injury and the neuroinflammation. [Display omitted] • Ibotenate led to excitotoxic-induced brain injury. • Ibotenate induced massive degranulation of brain mast cells and increased their number. • Ibotenate increased concentrations of activin A, IL-1β and IL-6 in brain tissue. • Cloxyquin dose-dependently ameliorated ibotenate-induced impairments in the cerebral gray and white matter. • Cloxyquin dose-dependently suppressed brain mast cells, and stimulated-levels of activin A, IL-1β and IL-6 in brain tissue. [ABSTRACT FROM AUTHOR]

Copyright of Croatian Review of Rehabilitation Research / Hrvatska Revija za Rehabilitacijska Istraživanja is the property of Croatian Review of Rehabilitation Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: Children with perinatal brain damage have a high prevalence of visual impairment. Stimulation of vision at a critical period can encourage brain plasticity and the recovery of impaired function. OBJECTIVE: The aim of our study was to investigate when is the critical period for visual stimulation in children with perinatal brain damage. METHODS: We compared 35 children within the first eight months of life (median age = 4 months) to 35 children aged between eight and thirty months (median age = 15 months), all with perinatal brain damage. All the children were attending an early intervention program at Mali dom, Zagreb, a rehabilitation centre for children with visual impairment. We compared the results from baseline and follow-up assessments of visual functions (grating acuity and contrast sensitivity). We also compared differences in change scores between the two groups. RESULTS: Our results have shown that children who commence a visual stimulation program within the first eight months of life had more improvement in both visual functions. This improvement is statistically significant in visual acuity (p = 0.048). CONCLUSIONS: These results indicate the importance of starting a visual stimulation program within the first eight months after birth. [ABSTRACT FROM AUTHOR]

Background: Cerebral intraventricular hemorrhage (IVH) is a major cause of severe neurodevelopmental impairment in preterm infants. To date, no therapy is available that prevents infants from developing serious neurological disability following IVH. Thus, to develop treatment strategies for IVH, it is essential to characterize the initial sequence of molecular events that leads to brain damage. In this study, we investigated extracellular hemoglobin (Hb) as a causal initiator of inflammation in preterm IVH. Methods: Using a preterm rabbit pup model, we investigated the molecular mechanisms and events following IVH. We also characterized the concentrations of cell-free Hb metabolites and pro-inflammatory mediators in the cerebrospinal fluid (CSF) of preterm human infants and rabbit pups. Finally, Hb metabolites were evaluated as causal initiators of inflammation in primary rabbit astrocyte cell cultures. Results: Following IVH in preterm rabbit pups, the intraventricular CSF concentration of cell-free methemoglobin (metHb) increased from 24 to 72 hours and was strongly correlated with the concentration of TNFα at 72 hours (r2 = 0.896, P <0.001). Also, the mRNA expression of TNFα, IL-1β, and Toll-like receptor-4 and TNFα protein levels were significantly increased in periventricular tissue at 72 hours, which was accompanied by extensive astrocyte activation (that is, glial fibrillary acidic protein (GFAP)staining). Furthermore, exposure of primary rabbit astrocyte cell cultures to metHb caused a dose-dependent increase in TNFα mRNA and protein levels, which was not observed following exposure to oxyhemoglobin (oxyHb) or hemin. Finally, a positive correlation (r2 = 0.237, P <0.03) between metHb and TNFα concentrations was observed in the CSF of preterm human infants following IVH. Conclusions: Following preterm IVH, increased metHb formation in the intraventricular space induces expression of pro-inflammatory cytokines. Thus, the formation of metHb might be a crucial initial event in the development of brain damage following preterm IVH. Accordingly, removal, scavenging, or neutralization of Hb could present a therapeutic opportunity and plausible approach to decreasing the damage in the immature brain following preterm IVH. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To examine brainstem auditory electrophysiology in term neonates under intensive care due to perinatal conditions other than hypoxia–ischemia. Methods: Maximum length sequence brainstem auditory evoked response was studied in term neonates in an intensive care unit. The amplitudes of wave components of the response were analysed to assess brainstem auditory electrophysiology. Results: The amplitudes of all wave components in the neonates under intensive care tended to be smaller than in those in normal term controls. Wave I amplitude was significantly reduced at all 91–910/s clicks (p < 0.05–0.01). The amplitudes of waves III and V were also reduced, respectively, at 227–910/s (all p <0.05) and at 455 and 910/s (both p <0.01). The amplitude reduction was slightly more significant at higher than lower click rates, but there were no significant differences in the slopes of wave I, III and V amplitude-rate functions between the neonates under intensive care and the controls. Conclusions: Wave amplitudes of maximum length sequence brainstem auditory evoked response were reduced in term neonates under intensive care due to perinatal conditions other than hypoxia–ischemia. Significance: Brainstem auditory electrophysiology is depressed in term neonates under intensive care, possibly due to collective adverse effects of perinatal conditions. The impairment to the neonatal, particularly rostral, brainstem due to other perinatal conditions is less severe than that due to hypoxia–ischemia previously reported. [Copyright &y& Elsevier]

Abstract: Glial cells play a crucial role in the pathomechanism of perinatal hypoxic-ischemic brain injury (HI) and are involved in the maintenance of a chronic state of inflammation that causes delayed neuronal damage. Activation of astrocytes is one factor prolonging brain damage and contributing to the formation of a glial scar that limits neuronal plasticity. In this context, the major astrocytic gap junction protein Connexin 43 (Cx43) has been ascribed various functions including regulation of astrocytic migration and proliferation. Here, we investigate glial responses like microglia/macrophages and astrocytic activation in a rat model of neonatal HI and characterize changes of these parameters upon transplantation of human umbilical cord blood cells (hUCB). As an alleviation of motor function in lesioned rats has previously been described in transplanted animals, we analyze the putative correlation between motor function and glial activation over time. The lesion-induced impairment of motor function, assessed by forelimb use bias, muscle strength and distal spasticity, was alleviated upon transplantation of hUCB short and long term. HI induced an acute inflammatory reaction with activation of microglia/macrophages and reactive astrogliosis associated with perilesional upregulation of Cx43 that slowly declined during the chronic post-ischemic phase. hUCB transplantation accelerated the regression of inflammatory events, narrowed the perilesional astrocytic wall and led to a downregulation of the investigated astrocytic proteins. Thus, in the immature brain, hUCB may indirectly reduce secondary cell death upon hypoxia-ischemia and facilitate post-ischemic plasticity through the attenuation of reactive gliosis. This article is part of a Special Issue entitled Electrical Synapses. [Copyright &y& Elsevier]

Abstract: Objective: To examine whether late preterm infants with perinatal problems are at risk of brainstem auditory impairment. Methods: 68 high-risk late preterm infants (gestation 33–36weeks) with perinatal problems or conditions were studied at term using maximum length sequence brainstem auditory evoked response. The controls were 41 normal term infants and 37 low-risk late preterm infants. Results: Compared with normal term infants, the high-risk late preterm infants demonstrated a significant abnormal increase in MLS BAER variables that mainly reflect more central function of the brainstem auditory pathway, including wave V latency, III–V and I–V interpeak intervals, and III–V/I–III interval ratio. The abnormalities were more significant at higher than at lower click rates. The slopes of MLS BAER-rate function for these variables were increased. Compared with low-risk late preterm infants, the high-risk infants showed similar, though slightly less significant, abnormalities, mainly a significant increase in III–V and I–V intervals. Conclusions: Maximum length sequence brainstem auditory evoked response components that mainly reflect central function of the auditory brainstem were abnormal at term in high-risk late preterm infants. Significance: More central regions of the auditory brainstem are impaired in high-risk late preterm infants, which is mainly caused by associated perinatal problems or conditions. [Copyright &y& Elsevier]

Abstract: The creatine-phosphocreatine shuttle is essential for the maintenance of cellular ATP, particularly under hypoxic conditions when respiration may become anaerobic. Using a model of intrapartum hypoxia in the precocial spiny mouse (Acomys cahirinus), the present study assessed the potential for maternal creatine supplementation during pregnancy to protect the developing brain from the effects of birth hypoxia. On day 38 of gestation (term is 39 days), the pregnant uterus was isolated and placed in a saline bath for 7.5 min, inducing global hypoxia. The pups were then removed, resuscitated, and cross-fostered to a nursing dam. Control offspring were delivered by caesarean section and recovered immediately after release from the uterus. At 24 h after birth hypoxia, the brains of offspring from dams fed a normal diet showed significant increases in lipid peroxidation as measured by the amount of malondialdehyde. In the cortical subplate, thalamus and piriform cortex there were significant increases in cellular expression of the pro-apoptotic protein BAX, cytoplasmic cytochrome c and caspase-3. When pregnant dams were fed the creatine supplemented diet, the increase in malondialdehyde, BAX, cytochrome c and caspase 3 were almost completely prevented, such that they were not different from control (caesarean-delivered) neonates. This study provides evidence that the neuroprotective capacity of creatine in the hypoxic perinatal brain involves abrogation of lipid peroxidation and apoptosis, possibly through the maintenance of mitochondrial function. Further investigation into these mechanisms of protection, and the long-term development and behavioural outcomes of such neonates is warranted. [Copyright &y& Elsevier]

Cerebral visual impairment (CVI) is one of the most common causes of bilateral visual loss, which frequently occurs due to perinatal brain injury. Vision in early life has great impact on acquisition of basic comprehensions which are fundamental for further development. Therefore, early detection of visual problems and early intervention is necessary. The aim of the present study is to determine specific visual functioning of children with perinatal brain damage and the influence of visual stimulation on development of functional vision at early age of life. We initially assessed 30 children with perinatal brain damage up to 3 years of age, who were reffered to our pediatric low vision cabinet in »Little house« from child neurologists, ophthalmologists Type and degree of visual impairment was determined according to functional vision assessment of each child. On the bases of those assessments different kind of visual stimulations were carried out with children who have been identified to have a certain visual impairment. Through visual stimulation program some of the children were stimulated with light stimulus, some with different materials under the ultraviolet (UV) light, and some with bright color and high contrast materials. Children were also involved in program of early stimulation of overall sensory motor development. Goals and methods of therapy were determined individually, based on observation of child's possibilities and need. After one year of program, reassessment was done. Results for visual functions and functional vision were compared to evaluate the improvement of the vision development. These results have shown that there was significant improvement in functional vision, especially in visual attention and visual communication. [ABSTRACT FROM AUTHOR]

Aim: We examined birth-related malpractice civil litigation cases in Japan to clarify the actual status related to the implementation of an obstetrical no-fault compensation system in 2009. Material & Methods: In this retrospective review, we analyzed legal and medical information from 64 cases with a delivery date after 1987 and a judgment date between April 1997 and March 2007. Results: The malpractice claim was accepted in 44 cases and rejected in 20 cases. The period from the delivery to the judgment date was lengthy (90.1 months overall). The average amount of damages awarded was ¥97 810 000 for cases of cerebral palsy (CP). Preterm births and less than 2500 g infants represented a higher incidence rate in the rejected cases. There were 32 cases (50.0%) with CP, 18 (28.1%) with infant death, 10 (15.6%) with neonatal death, and 4 (6.3%) with fetal death. Twenty-three of 44 accepted cases (52.3%) and 11/20 rejected cases (55.0%) had a gestational age of more than 33 weeks at birth and weighed more than 2000 g. Forced deliveries were performed in 45/64 cases (70.3%), and augmentation/induction of labor was performed in 28/64 cases (43.8%). There were 13/16 (81.3%) accepted cases that underwent vacuum and/or forceps extraction after labor augmentation/induction. Conclusions: More than half of our cases could be sufficient for a no-fault compensation system in Japan. Though the system is considered to have some problems that need to be solved, this finding suggests that many children and their families may benefit from the new system without having to file. [ABSTRACT FROM AUTHOR]

Once viewed as an isolated, immune-privileged organ, the central nervous system has undergone a conceptual change. Neuroinflammation has moved into the focus of research work regarding pathomechanisms underlying perinatal brain damage. In this review, we provide an overview of current concepts regarding perinatal brain damage and the role of inflammation in the disease pathomechanism. [ABSTRACT FROM AUTHOR]

OBJECTIVE. Preterm birth at <32 weeks' gestational age has a specific predilection for periventricular white matter injury. Early prediction of concomitant motor sequelae is a fundamental clinical issue. Recently, functional MRI was introduced as a noninvasive method for investigating the functional integrity of the neonatal brain. We aimed at implementing a unilateral passive forearm extension/flexion functional MRI paradigm in a routine clinical MRI setup to allow noninvasive mapping of the sensorimotor system in preterm infants and to relatethe functional data to structural and behavioral data. PATIENTS AND METHODS. Eight patients (median gestational age: 26.5 weeks; median birth weight: 885 g) were included. The functional MRI was performed at term-equivalent age (median: 39 weeks' postconceptional age) under chloral hydrate (50 mg/kg) sedation. In 5 of 8 patients, functional MRI data acquisition was successful. This resulted in 10 functional data sets (5 for passive stimulation of each forearm). RESULTS. Unilateral stimulation was associated with mainly bilateral activation of the primary sensorimotor cortex (n = 7 of 10 data sets), the prevailing hemodynamic response being a negative blood oxygenation level-dependent signal. Positive blood oxygenation level-dependent response or failure to activate the sensorimotor cortex (n = 3 of 10 data sets) were seen in those patients with aberrant structural/ behavioral indices. CONCLUSIONS. Our data show the feasibility of passive unilateral sensorimotor stimulation during neonatal clinical MRI protocols. The bilateral activation pattern observed at this age is compatible with a bilaterally distributed sensorimotor system. Our data validate initial accounts for a raised incidence of negative blood oxygenation leveldependent responses in the primary sensorimotor cortex at this developmental stage. The negative blood oxygenation level-dependent response is likely to reflect a reduction of the oxy/deoxy-hemoglobin ratio during a maturational stage characterized by rapid formation of synapses, yet ineffective processing. Positive blood oxygenation level-dependent responses or failure to activate the sensorimotor cortex may be an early indicator of abnormal development and will have to be followed up carefully. [ABSTRACT FROM AUTHOR]

Summary: We consider the range of childhood disabilities that have been attributed to perinatal hypoxic ischaemia at term and review the strength of evidence for each. The strongest evidence is for a causal link between acute profound hypoxic ischaemia and dyskinetic tetraplegic cerebral palsy (CP). Hemiplegic CP is not usually due to a perinatal hypoxic ischaemic insult at term; an important cause is focal cerebral infarction or ‘stroke’. Characteristically, diplegic CP is seen in ex-preterm children with periventricular leukomalacia. Ataxic CP is unlikely to be due to perinatal asphyxia. Recent careful follow-up studies have shown that childhood survivors of perinatal hypoxic ischaemia are at risk for cognitive deficits even in the absence of functional motor disorders. There is no evidence that, in isolation, either attention deficit hyperactivity disorder or autism is caused by hypoxic ischaemia. As effective neuroprotective therapies are introduced, notably cooling, it is possible that the prevalence of CP may be reduced. [Copyright &y& Elsevier]

Maternal infection is associated with perinatal brain damage, but effects on the cerebellum are not known in detail. In this study, we examined the effects of placental inflammation induced by administering lipopolysaccharide into the uterine artery of pregnant sheep at 134–136 days gestation. The fetal brain was collected 72 h later and compared to brains collected from age-matched untreated fetuses. Placental lipopolysaccharide treatment had substantial effects on the fetal cerebellum, including increasing the number of cells undergoing apoptosis, widespread lipid peroxidation, and extravasation of plasma albumin, suggesting compromise of the cerebellar blood-brain barrier. These effects may account for some of the learning and motor deficits that emerge in neonates from pregnancies compromised by infection. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To assess functional integrity of the auditory brainstem in neonates with transient low Apgar scores. Methods: Forty-two term infants were studied with brainstem auditory evoked response (BAER) using the maximum length sequence during the first month of life. All had transient low Apgar scores but no clinical signs of hypoxic-ischaemic encephalopathy (HIE). Results: The latencies of BAER waves I and III in these infants were similar to those of age-matched normal controls at all click rates (91/s, 227/s, 455/s and 910/s) during the period studied. Wave V latency was increased at 910/s on day 1 (P <0.01), but did not differ from that in the controls on any other days. I–V interval was increased significantly at 455/s and 910/s on day 1 (P <0.01 and 0.001) and day 3 (P <0.05 and 0.01). On days 5 and 7, BAER wave latencies and intervals were similar to those in the controls. On day 30, all latencies and intervals reached the values in the controls. No abnormalities were seen in BAER wave amplitude variables on any days. Conclusions: Neonates with transient low Apgar scores but without HIE had a significant increase in I–V interval at very high click rates on the first three days of life. Significance: Brainstem auditory function is sub-optimal during the first few days in neonates with transient low Apgar scores. [Copyright &y& Elsevier]

Aim: To examine brainstem auditory function in preterm infants after perinatal hypoxia-ischaemia (HI). Methods: Brainstem auditory evoked response (BAER) was studied at 37–42 wk postconceptional age in preterm infants who suffered perinatal HI, and were compared with those in preterm and term infants without any major perinatal problems. Results: None of the latencies of waves I, III and V in the BAER in preterm infants after perinatal HI differed significantly from those in preterm and term controls. There were also no significant differences in the I–V and I–III interpeak intervals between preterm infants after HI and the controls. However, III–V interval in infants after HI tended to increase, and was significantly longer than in term controls (p<0.01), although it did not differ significantly from that in preterm controls. Similarly, the III–V/I–III interval ratio was greater than in term controls (p<0.05), but was similar to that in preterm controls. All amplitude variables did not differ significantly from the controls.Conclusion: BAER in preterm infants after perinatal HI did not differ significantly from that in preterm infants without perinatal problems, but differed slightly from that in normal term infants. The prolonged III–V interval as compared with the term controls suggests a minor impairment in central auditory function. [ABSTRACT FROM AUTHOR]

Abstract: We recorded serially brainstem auditory evoked response (BAER) during the neonatal period in term infants who suffered perinatal asphyxia. The amplitudes of BAER components was analysed at 40dB above BAER threshold of each subject who had a threshold ⩽25dBnHL. No apparent changes in the amplitudes of waves I and III during the first 5 days after birth. The two wave amplitudes were slightly reduced thereafter. On day 30, the amplitudes were slightly smaller than in normal controls. No statistical significant differences were found in the two amplitudes between the infants after asphyxia and the controls on any days studied. In contrast, wave V amplitude showed a trend of reduction during the whole neonatal period. The amplitude was reduced slightly on the first day after birth, but reduced further on day 3 (ANOVA, P <0.01). Thereafter, the reduction persisted without any significant change. On day 30, wave V amplitude remained significantly smaller than in the controls (P <0.001). Compared to the controls, V/I amplitude ratio was slightly smaller during the neonatal period, but V/III amplitude ratio was significantly smaller on most of the days studied (P <0.05–0.01). The persistent reduction of wave V amplitude suggests a sustained neuronal damage of the auditory brainstem in infants after perinatal asphyxia. [Copyright &y& Elsevier]

Aim: To test if reventilation with room air (RA) or 100% oxygen (O 2 ) after asphyxia would differentially affect neuronal damage in different brain areas of newborn pigs. Methods: Anaesthetized piglets were subjected to 10 min asphyxia ( n =27) or served as time controls ( n =7). Reventilation started with either RA or O 2 for 1 h, and was continued with RA for an additional 1–3 h. Cortical or cerebellar blood flow was assessed with laser-Doppler flowmetry (LDF). Haematoxylin/eosin-stained sections from six brain regions were prepared for blinded neuropathological examination and scoring. Results: Asphyxia resulted in significant neuronal damage compared to time controls in all areas examined except the pons. O 2 ventilation elicited greater neuronal lesions in the hippocampus and the cerebellum but smaller damage in the basal ganglia compared to RA. The assessed physiological parameters including the LDF signals were similar in both ventilation groups, except for PaO 2 in the first hour of reventilation (RA 75±5 mmHg, O 2 348±57 mmHg; p Conclusion: O 2 toxicity after asphyxia was demonstrated in the piglet hippocampus and cerebellum but not in the cerebral cortex or basal ganglia. The observed regional differences may be associated with local haemodynamic factors. [ABSTRACT FROM AUTHOR]

Unlabelled: This study examined whether high presentation rates of clicks while recording brainstem auditory evoked responses (BAER) can improve the detection of central auditory impairment in asphyxiated neonates using the BAER. The BAER was analysed at different presentation rates of clicks within the first week after birth in 38 term neonates who suffered perinatal asphyxia. At the routinely used 21 s(-1) clicks all BAER wave latencies increased significantly (ANOVA, p < 0.05-0.01). After excluding five neonates who had a significantly elevated BAER threshold, only wave V latency increased slightly (p < 0.05). The interpeak intervals of I-V and III-V also increased slightly (both p < 0.05). Similar results were found at 51 s(-1) clicks. As the clicks were increased to 91 s(-1), the III-V interval increased more significantly (p < 0.01) and the III-V/I-III interval ratio also increased significantly (p < 0.01). In particular, wave V amplitude reduced more significantly than that in normal term controls (p < 0.01). Compared with values in the controls, wave V amplitude reduced by 4.5%, 12.2% and 24.7% at 21, 51 and 91 s(-1) clicks, respectively.Conclusion: Although a moderate increase in the rate (e.g. 51 s(-1)) while recording the BAER did not improve the detection of hypoxic-ischaemic auditory impairment, a significant increase (e.g. 91 s(-1)) did, which mainly indicates an abnormal reduction in wave V amplitude. [ABSTRACT FROM AUTHOR]

Objective:There is increasing evidence from animal experiments that mild hypothermia induced during or after cerebral ischemia might protect the immature brain from neuronal cell damage. However, the exact interrelation between the postischemic time delay and the degree of mild hypothermia by which to achieve neuroprotective effects on ischemic insults of different severity has not yet been elucidated systematically. To determine optimal neuroprotection, we studied the intention between these variables in a recently modified hippocampal slice model.Methods:We investigated the recovery of energy metabolism and protein synthesis (PSR) in hippocampal slices from mature fetal guinea pigs after 20, 30, or 40 minutes of oxygen and glucose deprivation (OGD). Hypothermia of varying degree was induced immediatey or 2 or 4 hours after OGD and lasted for 10 hours. Prolonged inhibition of PSR after ischemia has been shown to be a sensitive marker of neuronal cell damage.Results:Hypothermia initiated immediately after OGD significantly improved the recovery of energy metabolism and PSR. If there was a 2-hour delay in the onset of hypothermia, neuroprotection depended on the degree of hypothermia. Reduction of the incubation temperature to 31C diminished the disturbances of energy metabolism and PSR, whereas lowering the bath temperature to only 34C was not effective. Hypothermia induced 4 hours after OGD did not have any influence on the recovery of energy metabolism and PSR.Conclusion:We conclude that the effects of mild hypothermia on metabolic disturbances in hippocampal slices of mature fetal guinea pigs depended on the intervention delay and the degree of cooling. The shorter the postischemic intervention delay and the greater the degree of hypothermia, the better the neuroprotective effect seems to be. [ABSTRACT FROM PUBLISHER]

Objective:The purpose of the present study was to determine whether endotoxins (lipopolysaccharides, LPS) affect the fetal cardiovascular system in a way likely to cause brain damage.Methods:Thirteen fetal sheep were chronically instrumented at a mean gestational age of 107 ± 1 days. After control measurements of organ blood flow (microsphere method), blood gases, and acid base balance were obtained, seven of 13 fetuses received LPS (53 ± 3 μg/kg fetal weight) intravenously. Sixty minutes later, asphyxia was induced by occlusion of the maternal aorta for 2 minutes. Measurements of organ blood flows were made at -60, -1, +2, +4, +30, and +60 minutes.Results:Unlike in the control group, after LPS infusion there was a significant decrease in arterial oxygen saturation (-46%; P <.001) and pH (P <.001). In LPS-treated fetuses the portion of combined ventricular output directed to the placenta decreased significantly (-76%; P <.001), whereas output to the fetal body (+60%; P <.001), heart (+167%; P <.05), and adrenals (+229%; P <.01) increased. Furthermore, during asphyxia circulatory centralization was impaired considerably in LPS-treated fetuses, and there was clear evidence of circulatory decentralization. This decentralization caused a severe decrease in cerebral oxygen delivery by 70%. Wihin 30 minutes after induction of asphyxia five of seven LPS-treated featuses died, whereas all control fetuses recovered completely.Conclusions:Endotoxemia severely impaired fetal cardiovascular control during normoxia and asphyxia, resulting in a considerable decrease in cerebral oxygen delivery. These effects might have important effects in the development of fetal brain damage associated with intrauterine infection. [ABSTRACT FROM PUBLISHER]

Intracranial pressure and cerebral blood flow velocity were recorded in term healthy neonates during the first 3 days of life using non-invasive methods (LADD-fontanometry and cw-Doppler sonography). Intracranial pressure increased from 4.0 +/- 2.7 cm H2O to 5.8 +/- 2.7 cm H2O and maximal cerebral blood flow velocity in the anterior cerebral artery (ACA) increased from 33 cm/s to 58 cm/s as calculated from a Doppler shift of 0.63 to 1.10 kHz and vascular resistance decreased between the 1st and 3rd day of life. These alterations could not be demonstrated in the femoral artery. This is in accordance with other registrations obtained by different methods and under various conditions. They allow an explanation of some well known physiological phenomena like alterations of cranial volume and the structure of the bony skull in the first days of life. Furthermore, these physiological variations may have implications for the origin of cerebral damage during the perinatal period, especially of hypoxic-ischaemic encephalopathies. [ABSTRACT FROM AUTHOR]