scholarly journals Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury

2017 ◽  
Vol 39 (1-4) ◽  
pp. 182-191 ◽  
Author(s):  
Benjamin J. Blaise ◽  
Leslie Schwendimann ◽  
Vibol Chhor ◽  
Vincent Degos ◽  
Mark P. Hodson ◽  
...  
Keyword(s):  
Amino Acids ◽  
Developmental Process ◽  
Metabolic Phenotype ◽  
Brain Maturation ◽  
Diagnostic Biomarkers ◽  
Future Potential ◽  
Underlying Processes ◽  
The Brain ◽  
Excitotoxic Lesion ◽  
Over Time

Excitotoxicity plays a key role during insults to the developing brain such as neonatal encephalopathy, stroke, and encephalopathy of prematurity. Such insults affect many thousands of infants each year. Excitotoxicity causes frank lesions due to cell death and gliosis and disturbs normal developmental process, leading to deficits in learning, memory, and social integration that persist into adulthood. Understanding the underlying processes of the acute effects of excitotoxicity and its persistence during brain maturation provides an opportunity to identify mechanistic or diagnostic biomarkers, thus enabling and designing possible therapies. We applied mass spectrometry to provide metabolic profiles of brain tissue and plasma over time following an excitotoxic lesion (intracerebral ibotenate) to the neonatal (postnatal day 5) mouse brain. We found no differences between the plasma from the control (PBS-injected) and excitotoxic (ibotenate-injected) groups over time (on postnatal days 8, 9, 10, and 30). In the brain, we found that variations in amino acids (arginine, glutamine, phenylananine, and proline) and glycerophospholipids were sustaining acute and delayed (tertiary) responses to injury. In particular, the effect of the excitotoxic lesion on the normal profile of development was linked to alterations in a fingerprint of glycerophospolipids and amino acids. Specifically, we identified increases in the amino acids glutamine, proline, serine, threonine, tryptophan, valine, and the sphingolipid SM C26:1, and decreases in the glycerophospholipids, i.e., the arachidonic acid-containing phosphatidylcholine (PC aa) C30:2 and the PC aa C32:3. This study demonstrates that metabolic profiling is a useful approach to identify acute and tertiary effects in an excitotoxic lesion model, and generating a short list of targets with future potential in the hunt for identification, stratification, and possibly therapy.

The promise of developmental psychopathology: Past and present

2013 ◽  
Vol 25 (4pt2) ◽  
pp. 1215-1224 ◽  
Author(s):  
L. Alan Sroufe
Keyword(s):  
Developmental Psychopathology ◽  
Developmental Processes ◽  
Prevention And Intervention ◽  
Time Work ◽  
Underlying Processes ◽  
The Brain ◽  
Over Time

AbstractProgress in the field of developmental psychopathology is appraised in general and with regard to the particular lens of our understanding of the development of disorder. In general, the outpouring of research on various features of disorder and underlying processes could not have even been imagined 25 years ago. The progress is dazzling. At the same time, work on the development of disorders, beginning with antecedent patterns of adaptation, pales in comparison with work on the correlates of disorder. However, progress has been made. It is well established that the brain develops in the context of experience and that organism and environment continually interact over time. Something is now known about pathways leading to certain disorders and what initiates and impels individuals along them. If developmental psychopathology is to completely fulfill its promise of offering new ways of conceptualizing disorder and new guidance for prevention and intervention, much more work on developmental processes and a new way of exploring the development of disorder will be needed. Such a path is suggested.

scholarly journals Different Blood Metabolomics Profiles in Infants Consuming a Meat- or Dairy-Based Complementary Diet

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 388
Author(s):  
Minghua Tang ◽  
Nicholas E. Weaver ◽  
Lillian M. Berman ◽  
Laura D. Brown ◽  
Audrey E. Hendricks ◽  
...  
Keyword(s):  
Amino Acids ◽  
Dietary Intervention ◽  
Principal Component ◽  
Essential Amino Acids ◽  
Infant Growth ◽  
Serum Samples ◽  
Z Scores ◽  
Protein Rich ◽  
Over Time ◽  
Complementary Diet

Background: Research is limited in evaluating the mechanisms responsible for infant growth in response to different protein-rich foods; Methods: Targeted and untargeted metabolomics analysis were conducted on serum samples collected from an infant controlled-feeding trial that participants consumed a meat- vs. dairy-based complementary diet from 5 to 12 months of age, and followed up at 24 months. Results: Isoleucine, valine, phenylalanine increased and threonine decreased over time among all participants; Although none of the individual essential amino acids had a significant impact on changes in growth Z scores from 5 to 12 months, principal component heavily weighted by BCAAs (leucine, isoleucine, valine) and phenylalanine had a positive association with changes in length-for-age Z score from 5 to 12 months. Concentrations of acylcarnitine-C4, acylcarnitine-C5 and acylcarnitine-C5:1 significantly increased over time with the dietary intervention, but none of the acylcarnitines were associated with infant growth Z scores. Quantitative trimethylamine N-oxide increased in the meat group from 5 to 12 months; Conclusions: Our findings suggest that increasing total protein intake by providing protein-rich complementary foods was associated with increased concentrations of certain essential amino acids and short-chain acyl-carnitines. The sources of protein-rich foods (e.g., meat vs. dairy) did not appear to differentially impact serum metabolites, and comprehensive mechanistic investigations are needed to identify other contributors or mediators of the diet-induced infant growth trajectories.

scholarly journals Safety of Catheter Embolization of Pulmonary Arteriovenous Malformations—Evaluation of Possible Cerebrovascular Embolism after Catheter Embolization of Pulmonary Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia/Osler Disease by Pre- and Post-Interventional DWI

2021 ◽  
Vol 10 (4) ◽  
pp. 887
Author(s):  
Guenther Schneider ◽  
Alexander Massmann ◽  
Peter Fries ◽  
Felix Frenzel ◽  
Arno Buecker ◽  
...  
Keyword(s):  
Arteriovenous Malformations ◽  
Pulmonary Arteriovenous Malformations ◽  
B Values ◽  
Safe Method ◽  
Embolization Therapy ◽  
Catheter Embolization ◽  
Contrast Enhanced ◽  
Previously Treated ◽  
The Brain ◽  
Over Time

Background. This paper aimed to prospectively evaluate the safety of embolization therapy of pulmonary arteriovenous malformations (PAVMs) for the detection of cerebral infarctions by pre- and post-interventional MRI. Method One hundred and five patients (male/female = 44/61; mean age 48.6+/−15.8; range 5–86) with pre-diagnosed PAVMs on contrast-enhanced MRA underwent embolization therapy. The number of PAVMs treated in each patient ranged from 1–8 PAVMs. Depending on the size and localization of the feeding arteries, either Nester-Coils or Amplatzer vascular plugs were used for embolization therapy. cMRI was performed immediately before, and at the 4 h and 3-month post-embolization therapy. Detection of peri-interventional cerebral emboli was performed via T2w and DWI sequences using three different b-values, with calculation of ADC maps. Results Embolization did not show any post-/peri-interventional, newly developed ischemic lesions in the brain. Only one patient who underwent re-embolization and was previously treated with tungsten coils that corroded over time showed newly developed, small, diffuse emboli in the post-interventional DWI sequence. This patient already had several episodes of brain emboli before re-treatment due to the corroded coils, and during treatment, when passing the corroded coils, experienced additional small, clinically inconspicuous brain emboli. However, this complication was anticipated but accepted, since the vessel had to be occluded distally. Conclusion Catheter-based embolization of PAVMs is a safe method for treatment and does not result in clinically inconspicuous cerebral ischemia, which was not demonstrated previously.

scholarly journals The Role of Reduced Methionine in Mediating the Metabolic Responses to Protein Restriction Using Different Sources of Protein

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2609
Author(s):  
Han Fang ◽  
Kirsten P. Stone ◽  
Sujoy Ghosh ◽  
Laura A. Forney ◽  
Thomas W. Gettys
Keyword(s):  
Amino Acids ◽  
Dietary Protein ◽  
Target Genes ◽  
Protein Restriction ◽  
Metabolic Phenotype ◽  
Sulfur Amino Acids ◽  
Transcriptional Responses ◽  
Similar Reduction ◽  
Dietary Protein Restriction ◽  
Methionine Restriction

Dietary protein restriction and dietary methionine restriction (MR) produce a comparable series of behavioral, physiological, biochemical, and transcriptional responses. Both dietary regimens produce a similar reduction in intake of sulfur amino acids (e.g., methionine and cystine), and both diets increase expression and release of hepatic FGF21. Given that FGF21 is an essential mediator of the metabolic phenotype produced by both diets, an important unresolved question is whether dietary protein restriction represents de facto methionine restriction. Using diets formulated from either casein or soy protein with matched reductions in sulfur amino acids, we compared the ability of the respective diets to recapitulate the metabolic phenotype produced by methionine restriction using elemental diets. Although the soy-based control diets supported faster growth compared to casein-based control diets, casein-based protein restriction and soy-based protein restriction produced comparable reductions in body weight and fat deposition, and similar increases in energy intake, energy expenditure, and water intake. In addition, the prototypical effects of dietary MR on hepatic and adipose tissue target genes were similarly regulated by casein- and soy-based protein restriction. The present findings support the feasibility of using restricted intake of diets from various protein sources to produce therapeutically effective implementation of dietary methionine restriction.

scholarly journals What is special about L3 processing?

2013 ◽  
Vol 18 (2) ◽  
pp. 130-144 ◽  
Author(s):  
KEES DE BOT ◽  
CAROL JAENSCH
Keyword(s):  
Second Language ◽  
Language Processing ◽  
Language Use ◽  
Fundamental Question ◽  
Third Language ◽  
The Core ◽  
Dynamic Perspective ◽  
Core Issue ◽  
The Brain ◽  
Over Time

While research on third language (L3) and multilingualism has recently shown remarkable growth, the fundamental question of what makes trilingualism special compared to bilingualism, and indeed monolingualism, continues to be evaded. In this contribution we consider whether there is such a thing as a true monolingual, and if there is a difference between dialects, styles, registers and languages. While linguistic and psycholinguistic studies suggest differences in the processing of a third, compared to the first or second language, neurolinguistic research has shown that generally the same areas of the brain are activated during language use in proficient multilinguals. It is concluded that while from traditional linguistic and psycholinguistic perspectives there are grounds to differentiate monolingual, bilingual and multilingual processing, a more dynamic perspective on language processing in which development over time is the core issue, leads to a questioning of the notion of languages as separate entities in the brain.

GROUP 6 year outcome data in relation to antipsychotic medication

2016 ◽  
Vol 33 (S1) ◽  
pp. S50-S50
Author(s):  
W. Cahn ◽  
Keyword(s):  
Metabolic Syndrome ◽  
Cohort Study ◽  
Psychotic Disorders ◽  
Medication Use ◽  
Mood Stabilizer ◽  
Outcome Data ◽  
Longitudinal Cohort Study ◽  
Longitudinal Cohort ◽  
The Brain ◽  
Over Time

ObjectiveGenetic risk and outcome of psychoses (GROUP) is a 6 year longitudinal cohort study that focus on gene–environment vulnerability and resilience in patients with psychotic disorders, their unaffected family members and non-related controls. Its main aim is to elucidate etiological and pathogenetic factors that influence the onset and course of psychotic disorders. In this substudy, we will examine medication use over time, its relation with (the change in) metabolic syndrome status and effects on the brain.MethodsA consortium of four university psychiatric centers and their affiliated mental health care institutions, conducted the GROUP study. At baseline, 1120 patients, 1057 siblings, 919 parents and 590 healthy controls were included. After inclusion, participants, except parents, were evaluated again after three and six years of follow-up. Extensive assessment of genetic factors, environmental factors, medication use, metabolic parameters and outcome were performed. Moreover, brain imaging was performed in a subset of participants, using a 1.5 Tesla MRI scanner.ResultsAt baseline 65% of patients used atypical antipsychotics, 16% used conventional antipsychotics and 19% used clozapine. Siblings and controls used no antipsychotics. Forty-three percent of patients, 21.3% of siblings and 9.1% of controls used antidepressants; 43.9% of patients, 2.1% of siblings and none of the controls used a mood stabilizer. We are currently analyzing the medication data over time in relation to (change in) metabolic syndrome status and the effects on the brain.ConclusionGROUP is a longitudinal cohort study in patients with psychotic disorders, their healthy siblings and controls without psychosis. This naturalistic substudy examines medication use, its association with (change of) metabolic status and effects on the brain in subjects with (high risk of) psychosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Neurodevelopment in the first three years: implications for child development, professional practice and policy

2014 ◽  
Vol 9 (2) ◽  
pp. 154-164 ◽  
Author(s):  
Danya Glaser
Keyword(s):  
Brain Development ◽  
Brain Activity ◽  
Brain Maturation ◽  
Policy And Practice ◽  
Content Type ◽  
Key Issues ◽  
And Function ◽  
The Relationship ◽  
The Brain ◽  
Brain Connections

Purpose – The purpose of this paper is to outline brain structure and development, the relationship between environment and brain development and implications for practice. Design/methodology/approach – The paper is based on a selected review of the literature and clinical experience. Findings – While genetics determine the sequence of brain maturation, the nature of brain development and functioning is determined by the young child's caregiving environment, to which the developing brain constantly adapts. The absence of input during sensitive periods may lead to later reduced functioning. There is an undoubted immediate equivalence between every mind function – emotion, cognition, behaviour and brain activity, although the precise location of this in the brain is only very partially determinable, since brain connections and function are extremely complex. Originality/value – This paper provides an overview of key issues in neurodevelopment relating to the development of young children, and implications for policy and practice.

scholarly journals Utilization in vivo of glucose and volatile fatty acids by sheep brain for the synthesis of acidic amino acids

1966 ◽  
Vol 101 (3) ◽  
pp. 591-597 ◽  
Author(s):  
R M O'Neal ◽  
R E Koeppe ◽  
E I Williams
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Glutamic Acid ◽  
Aspartic Acid ◽  
Free Amino Acids ◽  
Free Amino ◽  
Specific Activity ◽  
Tricarboxylic Acid Cycle ◽  
Sheep Brain ◽  
The Brain

1. Free glutamic acid, aspartic acid, glutamic acid from glutamine and, in some instances, the glutamic acid from glutathione and the aspartic acid from N-acetyl-aspartic acid were isolated from the brains of sheep and assayed for radioactivity after intravenous injection of [2-(14)C]glucose, [1-(14)C]acetate, [1-(14)C]butyrate or [2-(14)C]propionate. These brain components were also isolated and analysed from rats that had been given [2-(14)C]propionate. The results indicate that, as in rat brain, glucose is by far the best precursor of the free amino acids of sheep brain. 2. Degradation of the glutamate of brain yielded labelling patterns consistent with the proposal that the major route of pyruvate metabolism in brain is via acetyl-CoA, and that the short-chain fatty acids enter the brain without prior metabolism by other tissue and are metabolized in brain via the tricarboxylic acid cycle. 3. When labelled glucose was used as a precursor, glutamate always had a higher specific activity than glutamine; when labelled fatty acids were used, the reverse was true. These findings add support and complexity to the concept of the metabolic; compartmentation' of the free amino acids of brain. 4. The results from experiments with labelled propionate strongly suggest that brain metabolizes propionate via succinate and that this metabolic route may be a limited but important source of dicarboxylic acids in the brain.

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