Association between fetoplacental Doppler results, placental pathology, and angiogenic factors among pregnant women with anxiety.

OBJECTIVE: This study aimed to evaluate whether state and trait anxiety among pregnant women were associated with fetoplacental Doppler findings, abnormal placental pathology, and placental angiogenic factors. MATERIALS AND METHODS: A total of 102 pregnant women at 32-35 gestational weeks were recruited and examined prospectively. State and trait anxiety were measured using the State-Trait Anxiety Inventory. Using Doppler ultrasound, pulsatility index (PI) of the umbilical artery (UA), middle cerebral artery (MCA), and uterine artery (UtA) and cerebroplacental ratio (CPR) were determined. Doppler parameters were converted into multiples of the median (MoM). Abnormal placental pathology was classified into 2 groups: vascular underperfusion (VU) and histological chorioamnionitis (HCA). Immunohistochemical analysis was performed to examine placental cells staining positive for placental growth factor (PLGF) and hypoxia-inducible factor-1-α (HIF-1α), which are markers for angiogenesis and hypoxic status, respectively. RESULTS: Women with high state anxiety scores had low MCA-PI MoM and CPR MoM, while those with high trait anxiety scores had low MCA-PI MoM. VU was associated with a higher incidence of high trait anxiety scores, and HCA was associated with a higher incidence of high state and trait anxiety scores. Regression analysis showed a relationship between maternal state anxiety on MCA-PI MoM and HCA after controlling for covariates. Maternal trait anxiety exhibited relationships with VU and HCA after adjustment. CONCLUSION: Our results demonstrated that maternal anxiety is associated with altered fetal cerebral blood flow and abnormal placental pathology but is not associated with uteroplacental insufficiency and placental angiogenic factors.

Prenatal intermittent hypoxia sensitizes the laryngeal chemoreflex, blocks serotoninergic shortening of the reflex, and reduces 5-HT3 receptor binding in the NTS in anesthetized rat pups.

We tested the hypothesis that exposure to intermittent hypoxia (IH) during pregnancy would prolong the laryngeal chemoreflex (LCR) and diminish the capacity of serotonin (5-hydroxytryptamine; 5-HT) to terminate the LCR. Prenatal exposure to IH was associated with significant prolongation of the LCR in younger, anesthetized, postnatal day (P) rat pups age P8 to P16 compared to control, room air (RA)-exposed rat pups of the same age. Serotonin microinjected into the NTS shortened the LCR in rat pups exposed to RA during gestation, but 5-HT failed to shorten the LCR in rat pups exposed to prenatal IH. Given these observations, we tested the hypothesis that prenatal hypoxia would decrease binding to 5-HT3 receptors in the nucleus of the solitary tract (NTS) where 5-HT acts to shorten the LCR. Serotonin 3 receptor binding was reduced in younger rat pups exposed to IH compared to control, RA-exposed rat pups in the age range P8 to P12. Serotonin 3 receptor binding was similar in older animals (P18-P24) regardless of gas exposure during gestation. The failure of the 5-HT injected into the NTS to shorten the LCR was correlated with a developmental decrease in 5-HT3 receptor binding in the NTS associated with exposure to prenatal IH. In summary, prenatal IH sensitized reflex apnea and blunted processes that terminate reflex apneas in neonatal rat pups, processes that are essential to prevent death following apneas such as those seen in babies who died of SIDS.

[Developmental amnesia and early brain damage: neuropsychology and neuroimaging]. / Amnesia del desarrollo y daño cerebral temprano: neuropsicologia y neuroimagen.

AIM: To contribute to neuropsychological profiling of developmental amnesia subsequent to bilateral damage to both hippocampi in early age. SUBJECTS AND METHODS: The total sample of 24 schoolchildren from both sexes is distributed in three groups: perinatal hypoxic-ischaemic encephalopathy and everyday complaints of memory in school age (n = 8); perinatal hypoxic-ischaemic encephalopathy without memory complaints (n = 7); and a group of typically developing (n = 9). All participants in every groups did have normal general intelligence and attention. Both clinical groups had, as another clinical consequence, spastic cerebral palsy (diplegia). Neuropsychological exam consisted on tests of general intelligence, attentional abilities, declarative memory and semantic knowledge. All participants had a brain magnetic resonance image and spectroscopy of hippocampi. Scheltens criteria were used for visual estimation of hippocampal atrophy. Parametric and non-parametric statistical contrasts were made. RESULTS: Despite preservation of semantic and procedural learning, declarative-episodic memory is impaired in the first group versus the other two groups. A significant proportion of bilateral hippocampal atrophy is only present in the first group versus the other two non-amnesic groups using Scheltens estimation on MRI. Two cases without evident atrophy did have diminished NAA/(Cho + Cr) index in both hippocampi. CONCLUSIONS: Taken together, these results contribute to delineate developmental amnesia as an specific impairment due to early partial bihippocampal damage, in agreement with previous studies. After diagnosis of developmental amnesia, a specific psychoeducational intervention must be made; also this impairment could be candidate for pharmacological trials in the future.

TITLE: Amnesia del desarrollo y daño cerebral temprano: neuropsicologia y neuroimagen.Objetivo. Contribuir a la descripcion de la amnesia del desarrollo como sindrome especifico en niños que sufrieron agresion temprana, pero no masiva, de ambos hipocampos. Sujetos y metodos. Muestra de 24 escolares de ambos sexos, de 6-16 años de edad. Se distribuye en tres grupos: pacientes afectos de encefalopatia hipoxico-isquemica perinatal, con paralisis cerebral espastica, inteligencia normal y fallos de memoria (n = 8); pacientes con similares caracteristicas, pero sin quejas de memoria (n = 7); y escolares sanos sin antecedentes de riesgo (n = 9) como grupo control. Se aplican escalas y tests para comprobar la normalidad intelectual y atencional, y para medir el perfil de rendimiento en tareas de memoria. En todos los sujetos, mediante resonancia magnetica, se estima la presencia y grado de atrofia hipocampica con la escala de Scheltens, y se calcula el indice espectroscopico NAA/(Cho + Cr). Resultados. El perfil neuropsicologico de los ocho pacientes del primer grupo es claramente sugestivo de amnesia del desarrollo, que contrasta con la normalidad en los otros grupos. En siete escolares con amnesia se constata bilateralmente algun grado de atrofia bihipocampica o disminucion significativa del indice NAA/(Cho + Cr). Conclusiones. La amnesia del desarrollo se caracteriza por afectacion de la memoria episodica con preservacion del aprendizaje semantico y procedimental. Se explica por daño parcial bihipocampico temprano. El correcto diagnostico permite una intervencion psicoeducativa especifica. En el futuro cabria ensayar terapias farmacologicas asociadas a la intervencion psicoeducativa.

Impaired expression of postsynaptic density proteins in the hippocampal CA1 region of rats following perinatal hypoxia.

Perinatal hypoxia is an important cause of brain injury amongst the newborn, such injury often resulting in an increased risk of impaired performance as regards learning and memory in later life for the affected individual. The postsynaptic density 95 (PSD-95) protein is a cytoskeletal specialization involved in the anchoring of N-methyl-d-aspartate (NMDA) receptors in postsynaptic neurons and has been reported to serve several important functions (e.g., synaptogenesis, synaptic plasticity and learning and memory performance) for the mammalian brain. Herein we investigated the long-term effects of perinatal hypoxia upon the complex of PSD-95 with NMDAR subunits by means of downstream signalling cAMP response element binding protein (CREB) phosphorylation at the Serine-133 locus (CREB(Ser-133) phosphorylation) within the hippocampal CA1 area (an essential integration area for mammalian learning and memory) within test-rat brains, as well as the effects upon afflicted-individual long-term learning and memory performance. We also assessed the therapeutic efficacy of dopamine D1/D5 receptor (D1/D5R) activation for such study animals. Perinatal hypoxia on postnatal day ten (P10) led to impaired performance as regards long-term spatial learning and memory (as determined on P45) associated with decreases in the level of CREB(Ser-133) phosphorylation and decreases in the expression of the complex of PSD-95 with NMDAR subunits (NR1, NR2A, and NR2B). In addition, activation of the D1/D5R via A68930 (a selective, CNS-permeable agonist of D1/D5Rs) administration (2 mg/kg/day, P17-23 inclusively) markedly attenuated the hypoxia-induced deleterious effects, suggesting an effective therapeutic efficacy for A68930. Our results demonstrate the long-term effects of perinatal hypoxia upon the developing brain and provide additional insights into the relative vulnerability of postsynaptic density (PSD) proteins to such insult, as well as the impairment of downstream transcription signalling CREB(Ser-133) phosphorylation following perinatal hypoxia. More importantly, D1/D5R activation following perinatal hypoxia may be an alternative therapeutic strategy to that which is currently available and may offer significant clinical potential for hypoxia sufferers.

Long-term influence of perinatal asphyxia on the social behavior in aging rats.

BACKGROUND: Various groups have been addressing the question of whether perinatal asphyxia (PA) affects the behavior of young animals, but no information is available on long-term effects of PA on the behavior in aged rats, although it has been postulated that PA may lead to neurological and psychiatric deficits in adult life. OBJECTIVE: We, therefore, decided to study the effects of PA on social and anxiety-related behaviors in 2-year-old rats, using a noninvasive animal model resembling the clinical situation. METHODS: For the behavioral studies, the open-field test, the elevated plus-maze test, and a social interaction test in pairs were performed. Magnetic resonance imaging of the brain was selected to rule out neuropathological changes due to the aging process per se, as well as asphyxia-induced pathologies in the brain areas known to play an important role in the modulation of behavior. RESULTS: The social interaction test revealed a statistically significant increase in the number of social grooming episodes and the time spent running alone, whereas the numbers of social sniffing and fighting episodes and the time spent running together were decreased in the asphyxiated group. The elevated plus- maze test revealed a higher presence of entries into the closed arm. Furthermore, sniffing and self-grooming episodes were significantly increased in the asphyxiated group. CONCLUSIONS: We found a significantly decreased social aggressiveness and an increased social contact behavior as well as increased anxiety levels in the asphyxiated animals. The present findings may provide important information on the long-term behavioral sequelae of PA in the aged individual.

Visual function in term infants with hypoxic-ischaemic insults: correlation with neurodevelopment at 2 years of age.

AIMS: To determine if there is any association between the findings of visual assessment performed at the age of 5 months and neurodevelopmental outcome at the age of 2 years in children who have sustained hypoxic-ischaemic insults. METHODS: Twenty nine term infants with hypoxic-ischaemic encephalopathy and/or brain lesions on neonatal magnetic resonance imaging (MRI) were prospectively evaluated. At 5 months of age all the infants had their visual function assessed using the Atkinson Battery of Child Development for Examining Functional Vision, which includes the assessments of optokinetic nystagmus (OKN), acuity, visual fields, fixation shift and phase and orientation reversal visual evoked potentials. At 2 years of age the children had a structured neurological evaluation and a Griffiths developmental assessment. RESULTS: There was good correlation between the extent of the early detected visual impairment and both neuromotor and global development. Children with more than three out of five abnormal visual tests at 5 months of age tended to have abnormal neurological examination results and abnormal developmental quotients. Children with three or fewer abnormalities tended to have developmental quotients in the normal range; the level of their performance, however, was still related to the number of visual tests passed. CONCLUSIONS: Individual visual tests can provide important prognostic information. While abnormal OKN and acuity were always associated with abnormal outcome, normal results on visual evoked potentials and fixation shift tended to be associated with normal outcome.

Behavioral and neurochemical sequelae in young rats of antenal hypoxia.

To test the hypothesis that perinatal hypoxia may have postnatal consequences via à vis learning memory, and neurochemical sequelae, we exposed pregnant Sprague-Dawley rats to 10.5% O2 for 4 h per day (0800-1200 h) or continuously from gestional day E15 to E20. On E20 we quantified ornithine decarboxylase activity and polyamine concentrations in fetal brain. We also conducted behavioral tests from postnatal day P3 to P110. Relatively mild antenatal hypoxia resulted in altered learning, memory, and delayed maturation of early developmental sensorimotor function. These behavioral changes disappeared at various postnatal ages, depending on the function. Perinatal hypoxia also altered the pharmacological response to dopaminergic drugs. In addition, antenatal hypoxia feminized a male nonreproductive sexual behavior, that of saccharin preference. Acute hypoxia also resulted in an increase in the enzyme ornithine decarboxylase and polyamines, which may affect brain development.

Behavioral sequelae in young rats of acute intermittent antenatal hypoxia.

Several studies have examined behavioral sequelae of acute or chronic pre- or postnatal hypoxia. However, few of these tested a large battery of behavioral functions, particularly those following relatively mild, intermittent hypoxia. Also, in few studies were the hypoxic pups cross-fostered or the experimenter blinded as to experimental group. In addition, in almost no studies were concomitant hypoxic-induced brain biochemicals measured. The present study tested the hypotheses that mild, intermittent antenatal hypoxia can lead to long-term alterations in neurobehavioral development, as well as neurochemical changes.

[Psychomotor development of children at risk with special reference to prenatal, intrapartum and postnatal hypoxia]. / Psychomotorische Entwicklung von Risikokindern unter Berücksichtigung prä-, intra- und postnataler Hypoxien.

In a prospective study the psychomotor development of an unselected collective of high risk newborn infants up to the end of the second year of life was examined. The proof of hypoxia was performed with the erythrocytic density test (EDT). The value of EDT showed a decline with the age of life, and it was independent of gestational age or of birthweight only at the first point of determination (cord blood, first or second day of life). Significant connections between the level of light red blood cells and the children's development could not be demonstrated, although the probability to develop psychomotor disabilities increased in the newborn with a positive value of EDT. The diagnostic value of EDT showed the best results for intrapartum and postnatal hypoxia. The highest specificity was calculated with 38.0%, if the sensitivity is 80.0%. In conclusion of these results it's not to be recommended to use the EDT alone for the prediction of individual prognosis of children.

Behavioral differences in the developing rat following postnatal anoxia or postnatally injected AF-64A, a cholinergic neurotoxin.

Rat pups were submitted postnatally to one of two procedures: a 25-min exposure to 100% nitrogen or an i.c.v. bilateral injection of AF-64A, 2 nmol contained in 1-microliter saline. Throughout further development of either group, their performance in passive and active avoidance tests and in amphetamine-induced stereotype behavior was followed and compared. Both groups exhibited hyperactivity which persisted until 42 days of age in the anoxia group and beyond 120 days in the AF-64A group. Both groups were equally inferior to controls in the passive avoidance test, but only the anoxia group was inferior to controls in the active avoidance test. Amphetamine-induced stereotype behavior was much less pronounced in the anoxia group relative to AF-64A-treated rats or to controls. The results suggest that the lesion induced by the neurotoxin is more specific and less widespread than the one caused by anoxia.