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PubMed2004

[DISC1 and schizophrenia].

Molecular mechanisms underlying the pathogenesis of schizophrenia remains elusive. The difficulty in accessing the mechanisms stems from, at least in part, multiple etiologies for schizophrenia. We have studied DISC1, as it was identified as a candidate gene for a schizophrenia-associated mental condition with the single etiology. Thus far, we have obtained evidence that DISC1 may have implications in neurodevelopment. This concept fits with many historical observations found for schizophrenia in association with neurodevelopmental abnormalities. DISC1 may become one of the key molecules in studying the pathogenesis of schizophrenia.

Animals↗
PubMed2004

Erythropoietin as a novel neuroprotectant.

PURPOSE: To provide an overview of the current knowledge on neuroprotective properties of Erythropoietin (Epo), mechanisms by which Epo produces neuroprotection, and signaling pathways regulated by Epo in the nervous system. METHODS: The Medline database was searched for articles on the neuroprotective properties of Epo. Experimental and clinical studies were systematically reviewed. RESULTS: In addition to promoting the survival, proliferation, and differentiation of immature erythroid cells, Epo and the Epo receptor (EpoR) have recently been shown to exist and function in the nervous system. The Epo/EpoR system plays a critical role in neurodevelopment and neuroprotection. Epo ameliorates or prevents neuronal injury by neuroprotective, anti-apoptotic, anti-inflammatory, anti-oxidant, angiogenic, neurogenic and neurotrophic effects in cell culture and animal models of neurological diseases. The clinical effectiveness of recombinant human Epo in ischemic stroke in human patients has also been reported recently. CONCLUSION: Recent studies suggest that Epo is a potential novel neurotherapeutic agent and further clinical studies are warranted.

Animals↗
PubMedDate not supplied

[A link between congenital malformations of the central nervous system and epilepsy in paediatric patients in Mexico].

INTRODUCTION: Since epilepsy is one of the most frequent causes of visits in Paediatric Neurology, attention must be given to one of the causes linked to it, namely congenital malformation, which is the second most common cause of epilepsy. To this end, different forms of congenital defects related to epilepsy in Paediatric medicine can be identified according to their neurodevelopment. AIMS: The purpose of this study was to determine the different congenital malformations associated to epilepsy in Paediatrics. PATIENTS AND METHODS: We took a sample consisting of 116 patients diagnosed as suffering from epilepsy associated with congenital malformations of the central nervous system, following an evaluation of imaging studies, magnetic resonance and computerised tomography brain scans; subjects were then grouped according to the normal embryonic chronological development of the human being. RESULTS: From the total number of cases, a selection was made according to age, where the predominant group was found in those below one year of age and in the group of school-age children, and migration disorders, where the main malformation included was lissencephaly; the other group was made up of proliferation disorders. Similarly, the associated types of epilepsy were the most common childhood epileptic syndromes, West and Lennox-Gastaut syndrome. The types of epileptic seizures that were found were partial seizures. CONCLUSIONS: The study outlined above shows congenital malformations of the central nervous system to be the main cause associated to epilepsy and the most sensitive neuroimaging study currently available is magnetic resonance. For this reason we suggest the use of this procedure in cases in which no apparent cause can be found so that this nosological entity can be defined to a greater degree of precision. Despite its multifactorial causation, being below 25 years of age and above 35 at the time of pregnancy is considered to constitute a higher potential risk, while no geographic location was found to predominate.

Adolescent↗
PubMedDate not supplied

[Neurodevelopmental disorders in children with an antecedent of subependymal/intraventricular hemorrhage at 3 years of age].

UNLABELLED: Intraventricular and subependymal hemorrhage are common complications among preterm infants. The aim of the present study was to assess its implication in the neurodevelopment at 3 years of age. MATERIAL AND METHODS: Cerebral ultrasonography with evidence of any stage of intraventricular hemorrhage (Papille's classification) during neonatal period and a neurologic evaluation at 3 years of age were performed on each patient. One hundred twenty four patients were enrolled and assigned to four groups according the intraventricular hemorrhage (IVH) stage: Grade 1, 14 patients, grade II, 84, grade III, 22, and grade IV nine patients. RESULTS: Morbility was similar for all groups; hydrocephalus was more frequent in group III (73%), and in group IV chronic pulmonary disease (77%) was more frequent. Forty five percent of the sample showed neurologic alterations with the greatest proportion in group IV (89%); OR for groups III and IV was 3.51 with a 95% confidence interval of (1.49, 8.28 p = 0.005). Grades III&IV showed lowest Terman Merril scores and grade IV scores were within the range of mental retardation. No statistical difference was found between grades at audition evaluation. CONCLUSIONS: Neurologic alterations were greater in poorer grades of IVH, and risk will increment for grades III and IV. Associated pathologies for IVH grades III and IV were hydrocephalus and chronic pulmonary disease.

Birth Weight↗
PubMed2004

Is iron deficiency in infants and young children common in Scandinavia and is there a need for enforced primary prevention?

A significant problem in diagnosing infants and young children with iron deficiency (ID) and iron deficiency anemia (IDA) is that it is not clear how the biochemical markers used correspond to physiological outcomes such as growth, neurodevelopment and morbidity. Thus, the prevalence of iron deficiency and iron deficiency anemia in infants and young children is difficult to assess and therefore not really known. Recent studies have shown that iron metabolism is subjected to developmental changes during infancy, which affect indicators of iron status. Hence, better defined cut-off values for the indicators used are needed and, in particular, how they are correlated to functional outcomes.

Adolescent↗
PubMedDate not supplied

[Ability of neonatal head circumference to predict long-term neurodevelopmental outcome].

AIM: We review the ability of head circumference (HC) at birth and head growth during the neonatal period to predict neurodevelopmental outcome, putting emphasis on new knowledge in this area. DEVELOPMENT: During infancy HC correlates closely with intracranial volume and constitutes an accurate predictor of cerebral volume. Both an abnormal head size at birth and an abnormal head growth during the neonatal period, can express brain damage or the presence of entities that involve varied degrees of neurological dysfunction in childhood. In general, the influence of head size or growth abnormalities on neurodevelopment is more related to the underlying etiology and/or the presence of structural diseases of the brain than with the HC alteration itself. HC evaluation is of particular interest in sick neonates, specially very low birth weight infants, regardless of whether they are normal or small for gestational age, and both during admission an during the first months of life. In these patients, HC catch-up within the first months of life represents a favorable neurodevelopmental prognostic factor. CONCLUSION: HC measuring and head growth evaluation constitute the most simple, inexpensive and quick available tools to assess the development of the central nervous system and identify neonates at risk of neurodevelopmental disorders.

Cephalometry↗
PubMed2004

Case-control association study of human netrin G1 gene in Japanese schizophrenia.

The exact etiology of schizophrenia remains undetermined but accumulating evidence suggests that disturbances in neurodevelopment may represent one contributory factor. Netrin G1, a recently cloned gene from the mouse, has been shown to play a potential role in the formation of neural circuitry. To determine whether this gene is involved in the development of psychosis, we performed a genetic association study of human netrin G1 gene in schizophrenia. First, we determined the human genomic structure of netrin G1 by direct comparisons between cDNA and genome sequences, and by database searches. For the subsequent examination of heterozygosity, we selected 10 single nucleotide polymorphisms (SNPs) for an association test in case (n = 180) and control (n = 180) samples. Among these SNPs, IVS8-1467C>T showed significant allelic association (nominal P = 0.020) with disease. This SNP is located in a haplotype block of approximately 40 kb and haplotypes in this block also displayed significant association (most significant P = 0.017). These findings suggest that netrin G1 or a nearby gene may contribute to the overall genetic risk for schizophrenia.

Adult↗
PubMed1992

The neonatal ICU graduate: Part II. Fundamentals of outpatient care.

Infants born prematurely require special surveillance and treatment in their first months and years of life. For many family physicians, the prospect of providing ongoing care for these infants seems overwhelming and difficult. Familiarity with the infant's hospital course and an understanding of basic principles of infant neurodevelopment, growth and health maintenance help family physicians provide skilled, thorough and capable care to high-risk newborns.

Ambulatory Care↗
PubMed1992

Behavioral effects of oral yohimbine in differentially reared nonhuman primates.

Eight unrestrained macaques were observed for 2 hours following either two oral doses of yohimbine (0.2 mg/kg and 2.0 mg/kg) or placebo administration. Four of the subjects were normally reared and four subjects had early maternal and social deprivation. In the normal subjects, yohimbine, at both doses, produced increased tension and enervation and decreased species-typical "normal" behaviors. In deprivation-reared subjects, low-dose yohimbine produced reductions in tension and enervation, and increases in "normal" behaviors. High doses of yohimbine diminished behavioral score differences between groups. The prominent increases in enervation observed in normally reared subjects suggests that yohimbine is not unequivocally anxiogenic. Moreover, early social deprivation may alter the pattern of response to yohimbine, perhaps as a result of aberrant neurodevelopment. This study reflects the role of experiential factors in determining patterns of affective response to putative anxiogenic agents.

Aging↗
PubMed2004

Intrauterine fetal transfusion.

The incidence of perinatal death resulting from rhesus Rh isoimmunization has dropped dramatically since the introduction of Rh immunoglobulin. However, Rh sensitization continues to be one of the leading causes of fetal anemia. Our patient is a 38-year-old woman; she gives a history of 2 uneventful pregnancies followed by 5 consecutive stillbirths. Investigations revealed an anti-D titre of 1/2048 and anti-C titre of 1/256. Ultrasound examination revealed fetal ascites at 18 weeks gestation. The fetus had a total of 9 successful intrauterine transfusions. She was delivered by an elective cesarean section at 34 weeks gestation; outcome was a healthy female baby weighing 2060 g. Examination at 9 month of age showed normal growth and neurodevelopment.

Adult↗
PubMed2005

[The social deficit in autism: focus on joint attention].

INTRODUCTION AND DEVELOPMENT: Autism is best thought of as a spectrum disorder with the dimensional components of social cognition, communication and flexibility varying between individuals meeting the criteria of autism. The core clinical feature that defines autism is a disturbance in social interaction which is not absolute and differs depending on a child's cognitive level, developmental stage, and the type of social structure in which they are observed. Social skills are under strong genetic influence with a continuous distribution of social interaction deficits in the general population with arbitrary cutoffs defining who is and is not affected with an autism spectrum disorder; this is the result of a complex interplay between numerous biological and environmental factors. Joint attention refers to the capacity of individuals to coordinate attention with a social partner in relation to some object or event and a disturbance in this early skill and in particular impairment in the ability to initiate joint attention, is a central symptom of autism. CONCLUSIONS: There are data to suggest that dorso-medial frontal cortex and anterior cingulate contribute to the development of an infant's ability to maintain representations of self, a social partner and an interesting object. The ability to engage frequently in social orienting behaviors and ultimately in numerous episodes of social attention coordination, or joint attention, may be a critical experience during a particular developmental window that serves to organize social neurodevelopment. A neurodevelopmental model explaining how these early deficits in social cognition may lead to autism is reviewed.

Autistic Disorder↗
PubMed2005

[A case of fetal alcohol effects with orofacial cleft].

Maternal alcohol use during pregnancy may result in facial dysmorphism, growth retardation and central nervous system deficits. This has been found in infants ranging from fetal alcohol effects (FAE) to fetal alcohol syndrome (FAS), or alcohol related neurodevelopment disorders (ARND) and alcohol related birth defects (ARBD). In this study, we report a FAE case with orofacial cleft due to mother's alcohol use during her pregnancy. A 32-year-old Japanese woman, para2, gravida3. She was drinking alcohol while this pregnancy. At 39th week, a girl was delivered vaginally. Her birth weight is 3860gr. Apgar score is seven points at one minutes and eight points at 10 minutes. Orofacial cleft and sinus tachycardia were diagnosed postnatally. From a brain-computed tomography (CTscan), it showed a normal finding. Karyotype was normal female phenotype (46, XX). It is important to note that the obstetrician had to advise the women not to have alcohol use during pregnancy in order to prevent her baby from fetal alcohol effects or toxic effect of alcohol on the fetus.

Adult↗
PubMedDate not supplied

Neonatal morbidity and outcome of live born premature babies after attempted illegal abortion with misoprostol.

UNLABELLED: Misoprostol is a synthetic prostaglandin currently employed to induce labor. Association with illegal abortion has been reported; however, neonatal outcome and morbidity after a failed attempt of abortion has not been described. OBJECTIVES: To report the association between misoprostol self-medication and preterm labor and to assess perinatal risk factors, morbidity and early outcomes. METHODS: We conducted a prospective study of all very low birth weight (VLBW) infants delivered in Hospital Fernando Fonseca, during a 5-year period. VLBW infants were assigned to misoprostol group (MG) when preterm delivery was attributed to misoprostol and matched with newborns with similar gestational age, birth- weight, and gender. RESULTS: During the study period 311 VLBW infants were born. Nineteen belonged to misoprostol group (MG) and 58 were selected for controls. Mothers from MG were significantly younger (21.5 vs 27.5, p = 0.001) and from African origin (74 vs 31%, p = 0.006), had significantly less prenatal care (21 vs 67%, p = 0.000), less antenatal steroids (5 vs 50%, p = 0.001), and were delivered less often by C-section (11 vs 60%, p = 0.000). MG infants had significantly higher rates of patent ductus arteriosus (58 vs 29%, p = 0.031) and chronic lung disease (47 vs 14%, p = 0.026). Mortality rate at 3 months was similar in both groups, but the incidence of abnormal neurodevelopment at 1 year of age was significantly higher in the MG (50 vs 16%, p= 0.02). COMMENTS: The worse outcome of MG infants seems to be determined by prenatal, natal, and postnatal factors and we believe that misoprostol is probably a significant adjuvant cofactor.

Abortifacient Agents, Nonsteroidal↗
PubMed2005

Central N-acetyl aspartylglutamate deficit: a possible pathogenesis of schizophrenia.

The "glutamate hypothesis" of schizophrenia has emerged from the finding that phencyclidine (PCP) induces psychotic-like behaviors in rodents, possibly by blocking the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, thereby causing increased glutamate release. N-acetyl aspartylglutamate (NAAG), an endogenous peptide abundant in mammalian nervous systems, is localized in certain brain cells, including cortical and hippocampal pyramidal neurons. NAAG is synthesized from N-acetylaspartate (NAA) and glutamate, and NAA availability may limit the rate of NAAG synthesis. Although NAAG is known to have some neurotransmitter-like functions, NAA does not. NAAG is a highly selective agonist of the type 3 metabotropic glutamate receptor (mGluR3, a presynaptic autoreceptor) and can inhibit glutamate release. In addition, at low levels, NAAG is an NMDA receptor antagonist, and blocking of NMDA receptors may increase glutamate release. Taken together, low central NAAG levels may antagonize the effect of glutamate at NMDA receptors and decrease its agonistic effect on presynaptic mGluR3; both activities could increase glutamate release, similar to the increase demonstrated in the PCP model of schizophrenia. In this report, it is suggested that the central NAAG deficit, possibly through decreased synthesis or increased degradation of NAAG, may play a role in the pathogenesis of schizophrenia. Evidence is presented and discussed from magnetic resonance, postmortem, animal model, schizophrenia treatment, and genetic studies. The central NAAG deficit model of schizophrenia could explain the disease process, from the perspectives of both neurodevelopment and neurodegeneration, and may point to potential treatments for schizophrenia.

Animals↗
PubMed2005

Effects of maternal deprivation on melatonin production and cognition in adolescent male and female rats.

OBJECTIVES: It is known that maternal deprivation (MD) may alter cognitive functions such as learning and memory in adult life by effecting normal growth and development. However, the mechanisms of these cognitive alterations are unknown. The aim of this study is to investigate the effects of maternal deprivation on cognition and melatonin production in adolescent male and female rats. METHODS: The litters were separated daily from their mothers for 6 hours on postnatal days 2 to 20. The spatial memory performance was evaluated using a Morris water maze between the postnatal 26th and 32nd days. Plasma melatonin levels were determined on postnatal days 42. RESULTS: MD-rats had longer escape latencies at the second, third and fifth days of training days and spend significantly less time in probe trial, compared to control animals. MAIN FINDINGS: The repeated maternal deprivation caused low blood melatonin levels and there was a significant negative correlation between blood melatonin levels and spatial memory performance in both of male and female adolescent rats. CONCLUSION: These results suggest an association between melatonin production and neurodevelopment. Further studies are needed to determine the interaction between maternal deprivation and pineal gland maturation/function.

Animals↗
PubMedDate not supplied

Transient hyperammonemia in a neonate.

Neonatal hyperammonemia is a medical emergency requiring a multidisciplinary teamwork for early recognition and early treatment. The causes of neonatal hyperammonemia vary. The transient hyperammonemia of the neonate (THAN) occurs mostly in premature babies, and the prognosis is usually better than for urea cycle disorders. Here we present a near-term premature male infant with THAN. He exhibited the symptoms during the first 36 hours of life and survived after continuous arteriovenous hemodiafiltration (CAVHD). Nutritional support and sodium benzoate were also given. The diagnosis was based on laboratory tests. Long-term follow-up of neurodevelopment was suggested.

Anti-Infective Agents↗
PubMedDate not supplied

[Monozygous female twins discordant for a pattern of X chromosome inactivation as a model for study on X-linked intellectual traits].

Ring the last decades, numerous genes for general cognitive ability were identified on human X-chromosome. They were discovered primarily because of X-linked mutations causing nonspecific mental retardation in males. Evidence for imprinted loci on the X chromosome affecting neurodevelopment was found in studies on 45,X females. Investigation of transmission of X-linked traits in normal individuals might further contribute to problem of shaping human being's mind ability. We suggest monozygous female twins discordant for a parent-of-origin of the X chromosome inactivation to be a proper subject for such explorations.

Diseases in Twins↗
PubMed2005

Erythropoietin enhances neurological recovery after experimental spinal cord injury.

PURPOSE: Erythropoietin is a hematopoietic growth factor. It is also involved in neurodevelopment and neuroprotection. The purpose of this study was to evaluate the effectiveness of erythropoietin in enhancing the neurological recovery following experimental spinal cord injury. METHODS: Rats were randomly divided into 4 groups. Group 1 received only laminectomy. Group 2, 3, and 4 have undergone a spinal contusion injury of 50 gr/cm. Group 2 received no medication. Group 3 received 30 mg/kg methylprednisolone. Group 4 received 5000 IU/kg recombinant human erythropoietin. Following injury, neurological recovery was evaluated for 14 days, using a swimming test. RESULTS: At day 1, there was no difference between mean motor scores of group 2, 3, and 4. Following day 1, rats in group 4 exhibited a marked improvement in motor score, and this was maintained throughout the study. When compared to group 2, mean motor score of group 4 was significantly higher at day 4, 7, 10, and 14. When compared to group 3, mean motor score of group 4 was significantly higher at day 7, 10, and 14. CONCLUSION: These findings suggest that erythropoietin enhances neurological recovery following spinal cord injury and it seems to be more effective than methylprednisolone at the given doses.

Animals↗