Cerebral Oxygen Metabolism in Newborns

PEDIATRICS ◽  
1993 ◽  
Vol 92 (1) ◽  
pp. 99-104
Author(s):  
Denis I. Altman ◽  
Jeffrey M. Perlman ◽  
Joseph J. Volpe ◽  
William J. Powers
Keyword(s):  
Brain Injury ◽  
Preterm Infants ◽  
Treatment Strategies ◽  
Oxygen Metabolism ◽  
Therapeutic Interventions ◽  
Term Infants ◽  
Newborn Brain ◽  
Positron Emission ◽  
The Brain ◽  
Human Neonates

Objective. A better understanding of the developmental changes in brain energy metabolism that occur in human neonates is critically important for designing rational treatment strategies that ensure an adequate supply of nutrients to the brain and minimize deleterious side effects of therapeutic interventions in sick newborns. Methods. Cerebral metabolic rate for oxygen (CMRO2) was measured with positron emission tomography in 11 sick newborns of different gestational ages. Results. In five preterm infants, mean hemispheric CMRO2 was 0.06 to 0.54 mL 100 g-1 min-1. Two of these preterm infants with virtually absent CMRO2 (0.06 mL 100 g-1 min-1) had minimal or no evidence of parenchymal brain injury detected in the newborn period. In six term infants, mean hemispheric CMRO2 was 0.0 to 1.3 mL 100 g-1 min-1. Two with no neurological disease had mean hemispheric CMRO2 of 0.4 and 0.7 mL 100 g-1 min-1 and were normal at 6 and 7 months, respectively. Conclusions. CMRO2 in four newborns who had minimal or no detectable brain injury was considerably below the threshold for brain viability in adults of 1.3 mL 100 g-1 min-1. This indicates that energy requirements in fetal and newborn brain are minimal or can be met by nonoxidative metabolism.

scholarly journals Developments in Tau PET Imaging

2014 ◽  
Vol 41 (5) ◽  
pp. 547-553 ◽  
Author(s):  
Eduardo Rigon Zimmer ◽  
Antoine Leuzy ◽  
Serge Gauthier ◽  
Pedro Rosa-Neto
Keyword(s):  
Therapeutic Interventions ◽  
Imaging Agents ◽  
Cognitive Assessments ◽  
Molecular Subgroup ◽  
Future Directions ◽  
Tau Imaging ◽  
Positron Emission ◽  
The Brain ◽  
Pet Radiopharmaceuticals

ABSTRACTThe presence of neurofibrillary tangles in the brain is a hallmark feature of several neurodegenerative diseases termed “tauopathies,” including Alzheimer’s disease (AD) and the tau molecular subgroup of frontotemporal lobar degeneration (FTLD-tau). Recently, several positron emission tomography (PET) radiopharmaceuticals targeting abnormal conformations of the tau protein have been developed. To date, six novel tau imaging agents—[18F]THK523, [18F]THK5105, [18F]THK5117, [18F]T807, [18F]T808, and [11C]PBB3—have been described and are considered promising as potential tau radioligands. Tau imaging agents offer the opportunity of in vivo topographical mapping and quantification of tau aggregates in parallel with clinical and cognitive assessments. As such, tau imaging is considered of key importance for progress toward earlier and more accurate diagnosis of tauopathies as well as for the monitoring of therapeutic interventions and drug development. Here, we shed light on the most important developments in tau radiopharmaceuticals, highlighting challenges, possibilities and future directions.

scholarly journals Vancomycin Is Protective in a Neonatal Mouse Model of Staphylococcus epidermidis-Potentiated Hypoxic-Ischemic Brain Injury

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Jacqueline C. Y. Lai ◽  
Pernilla Svedin ◽  
C. Joakim Ek ◽  
Amin Mottahedin ◽  
Xiaoyang Wang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Mouse Model ◽  
Preterm Infants ◽  
Staphylococcus Epidermidis ◽  
Neonatal Mouse ◽  
Neurodevelopmental Outcomes ◽  
Ischemic Brain ◽  
Content Type ◽  
Increased Risk ◽  
The Brain

ABSTRACT Infection is correlated with increased risk of neurodevelopmental sequelae in preterm infants. In modeling neonatal brain injury, Toll-like receptor agonists have often been used to mimic infections and induce inflammation. Using the most common cause of bacteremia in preterm infants, Staphylococcus epidermidis, we present a more clinically relevant neonatal mouse model that addresses the combined effects of bacterial infection together with subsequent hypoxic-ischemic brain insult. Currently, there is no neuroprotective treatment for the preterm population. Hence, we tested the neuroprotective effects of vancomycin with and without adjunct therapy using the anti-inflammatory agent pentoxifylline. We characterized the effects of S. epidermidis infection on the inflammatory response in the periphery and the brain, as well as the physiological changes in the central nervous system that might affect neurodevelopmental outcomes. Intraperitoneal injection of postnatal day 4 mice with a live clinical isolate of S. epidermidis led to bacteremia and induction of proinflammatory cytokines in the blood, as well as transient elevations of neutrophil and monocyte chemotactic cytokines and caspase 3 activity in the brain. When hypoxia-ischemia was induced postinfection, more severe brain damage was observed in infected animals than in saline-injected controls. This infection-induced inflammation and potentiated brain injury was inoculum dose dependent and was alleviated by the antibiotic vancomycin. Pentoxifylline did not provide any additional neuroprotective effect. Thus, we show for the first time that live S. epidermidis potentiates hypoxic-ischemic preterm brain injury and that peripheral inhibition of inflammation with antibiotics, such as vancomycin, reduces the extent of brain injury.

Brain-Oriented Care in the NICU: A Case Study

2014 ◽  
Vol 33 (5) ◽  
pp. 263-267 ◽  
Author(s):  
Lisa Bader
Keyword(s):  
Preterm Infant ◽  
Preterm Infants ◽  
Premature Infants ◽  
Normal Development ◽  
Developmental Outcome ◽  
Medical Field ◽  
Term Infants ◽  
Developmental Care ◽  
The Brain

With the advances of technology and treatment in the field of neonatal care, researchers can now study how the brains of preterm infants are different from full-term infants. The differences are significant, and the outcomes are poor overall for premature infants as a whole. Caregivers at the bedside must know that every interaction with the preterm infant affects brain development—it is critical to the developmental outcome of the infant. The idea of neuroprotection is not new to the medical field but is a fairly new idea to the NICU. Neuroprotection encompasses all interventions that promote normal development of the brain. The concept of brain-oriented care is a necessary extension of developmental care in the NICU. By following the journey of 26-week preterm twin infants through a case study, one can better understand the necessity of brain-oriented care at the bedside.

scholarly journals A novel imaging ligand as a biomarker for mutant huntingtin-lowering in Huntington's disease

2021 ◽  
Author(s):  
Daniele Bertoglio ◽  
Jonathan Bard ◽  
Manuela Hessmann ◽  
Longbin Liu ◽  
Annette Gaertner ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Therapeutic Interventions ◽  
Non Invasive ◽  
Positron Emission ◽  
Trinucleotide Expansion ◽  
Imaging Markers ◽  
The Brain ◽  
Polyq Tract

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene that encodes the pathologic mutant HTT (mHTT) protein with an expanded polyglutamine (PolyQ) tract. While several therapeutic programs targeting mHTT expression have advanced to clinical evaluation, no method is currently available to visualize mHTT levels in the living brain. Here we demonstrate the development of a positron emission tomography (PET) imaging radioligand with high affinity and selectivity for mHTT aggregates. This small molecule radiolabeled with 11C ([11C]CHDI-180R) enables non-invasive monitoring of mHTT pathology in the brain and can track region- and time-dependent suppression of mHTT in response to therapeutic interventions targeting mHTT expression. We further show that therapeutic agents that lower mHTT in the striatum have a functional restorative effect that can be measured by preservation of striatal imaging markers, enabling a translational path to assess the functional effect of mHTT lowering.

scholarly journals Multimodal magnetic resonance imaging predicts regional amyloid- β burden in the brain

2020 ◽  
Author(s):  
Anusha Rangarajan ◽  
Minjie Wu ◽  
Naomi Joseph ◽  
Helmet T. Karim ◽  
Charles Laymon ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Amyloid Β ◽  
Structural Mri ◽  
In Vivo Detection ◽  
Positron Emission ◽  
Large Numbers ◽  
Early Markers ◽  
Fluid Attenuated Inversion Recovery ◽  
The Brain

AbstractAlzheimer’s disease (AD) is the most common cause of dementia and identifying early markers of this disease is important for prevention and treatment strategies. Amyloid - β protein deposition is one of the earliest detectable pathological changes in AD. But in-vivo detection of amyloid - β using positron emission tomography (PET) is hampered by high cost and limited geographical accessibility. These factors can become limiting when PET is used to screen large numbers of subjects into prevention trials when only a minority are expected to be amyloid- β - positive. Structural MRI is advantageous; as it is relatively inexpensive and more accessible. Thus it could be widely used in large studies, even when frequent or repetitive imaging is necessary. We used a machine learning, pattern recognition, approach using intensity-based features from individual and combination of MR modalities (T1 weighted, T2 weighted, T2 fluid attenuated inversion recovery [FLAIR], susceptibility weighted imaging) to predict voxel-level amyloid- β in the brain. The MR- amyloid β relation was learned within each subject and generalized across subjects using subject–specific features (demographic, clinical, and summary MR features). When compared to other modalities, combination of T1-weighted, T2-weighted FLAIR, and SWI performed best in predicting the amyloid- β status as positive or negative. T2- weighted performed the best in predicting change in amyloid- β over two timepoints. Overall, our results show feasibility of amyloid- β prediction by MRI.

scholarly journals Spreading Depolarization Waves in Neurological Diseases: A Short Review about its Pathophysiology and Clinical Relevance

2019 ◽  
Vol 17 (2) ◽  
pp. 151-164
Author(s):  
Yağmur Çetin Taş ◽  
İhsan Solaroğlu ◽  
Yasemin Gürsoy-Özdemir
Keyword(s):  
Traumatic Brain Injury ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Experimental Studies ◽  
Treatment Strategies ◽  
Short Review ◽  
Therapeutic Interventions ◽  
Target Area ◽  
Spreading Depolarization ◽  
Lesion Growth

Lesion growth following acutely injured brain tissue after stroke, subarachnoid hemorrhage and traumatic brain injury is an important issue and a new target area for promising therapeutic interventions. Spreading depolarization or peri-lesion depolarization waves were demonstrated as one of the significant contributors of continued lesion growth. In this short review, we discuss the pathophysiology for SD forming events and try to list findings detected in neurological disorders like migraine, stroke, subarachnoid hemorrhage and traumatic brain injury in both human as well as experimental studies. Pharmacological and non-pharmacological treatment strategies are highlighted and future directions and research limitations are discussed.

scholarly journals A Model for the Coupling between Cerebral Blood Flow and Oxygen Metabolism during Neural Stimulation

1997 ◽  
Vol 17 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Richard B. Buxton ◽  
Lawrence R. Frank
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabolic Rate ◽  
Oxygen Metabolism ◽  
Neural Stimulation ◽  
Brain Capillaries ◽  
Tight Coupling ◽  
Positron Emission ◽  
General Mathematical Model ◽  
The Brain

A general mathematical model for the delivery of O2 to the brain is presented, based on the assumptions that all of the brain capillaries are perfused at rest and that all of the oxygen extracted from the capillaries is metabolized. The model predicts that disproportionately large changes in blood flow are required in order to support small changes in the O2 metabolic rate. Interpreted in terms of this model, previous positron emission tomography (PET) studies of the human brain during neural stimulation demonstrating that cerebral blood flow (CBF) increases much more than the oxygen metabolic rate are consistent with tight coupling of flow and oxidative metabolism. The model provides a basis for the quantitative interpretation of functional magnetic resonance imaging (fMRI) studies in terms of changes in local CBF.

scholarly journals Defining Ischemic Burden after Traumatic Brain Injury Using 15O PET Imaging of Cerebral Physiology

2004 ◽  
Vol 24 (2) ◽  
pp. 191-201 ◽  
Author(s):  
Jonathan P Coles ◽  
Tim D Fryer ◽  
Peter Smielewski ◽  
Kenneth Rice ◽  
John C Clark ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Blood Flow ◽  
Brain Injury ◽  
Head Injury ◽  
A Priori ◽  
Oxygen Metabolism ◽  
Oxygen Extraction Fraction ◽  
Statistical Accuracy ◽  
Positron Emission ◽  
Cerebral Physiology

Whereas postmortem ischemic damage is common in head injury, antemortem demonstration of ischemia has proven to be elusive. Although 15O positron emission tomography may be useful in this area, the technique has traditionally analyzed data within regions of interest (ROIs) to improve statistical accuracy. In head injury, such techniques are limited because of the lack of a priori knowledge regarding the location of ischemia, coexistence of hyperaemia, and difficulty in defining ischemic cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) levels. We report a novel method for defining disease pathophysiology following head injury. Voxel-based approaches are used to define the distribution of oxygen extraction fraction (OEF) across the entire brain; the standard deviation of this distribution provides a measure of the variability of OEF. These data are also used to integrate voxels above a threshold OEF value to produce an ROI based upon coherent physiology rather than spatial contiguity (the ischemic brain volume; IBV). However, such approaches may suffer from poor statistical accuracy, particularly in regions with low blood flow. The magnitude of these errors has been assessed in modeling experiments using the Hoffman brain phantom and modified control datasets. We conclude that this technique is a valid and useful tool for quantifying ischemic burden after traumatic brain injury.

scholarly journals Incidence and Mechanisms of Cerebral Ischemia in Early Clinical Head Injury

2004 ◽  
Vol 24 (2) ◽  
pp. 202-211 ◽  
Author(s):  
Jonathan P. Coles ◽  
Tim D. Fryer ◽  
Piotr Smielewski ◽  
Doris A. Chatfield ◽  
Luzius A. Steiner ◽  
...  
Keyword(s):  
Head Injury ◽  
Oxygen Metabolism ◽  
Jugular Bulb ◽  
Emission Tomography ◽  
Oxygen Extraction Fraction ◽  
Ischemic Brain ◽  
Cerebral Oxygen Metabolism ◽  
Extraction Fraction ◽  
Positron Emission ◽  
The Brain

Antemortem demonstration of ischemia has proved elusive in head injury because regional CBF reductions may represent hypoperfusion appropriately coupled to hypometabolism. Fifteen patients underwent positron emission tomography within 24 hours of head injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), and oxygen extraction fraction (OEF). We estimated the volume of ischemic brain (IBV) and used the standard deviation of the OEF distribution to estimate the efficiency of coupling between CBF and CMRO2. The IBV in patients was significantly higher than controls (67 ± 69 vs. 2 ± 3 mL; P < 0.01). The coexistence of relative ischemia and hyperemia in some patients implies mismatching of perfusion to oxygen use. Whereas the saturation of jugular bulb blood (SjO2) correlated with the IBV ( r = 0.8, P < 0.01), SjO2 values of 50% were only achieved at an IBV of 170 ± 63 mL (mean ± 95% CI), which equates to 13 ± 5% of the brain. Increases in IBV correlated with a poor Glasgow Outcome Score 6 months after injury (ρ = −0.6, P < 0.05). These results suggest significant ischemia within the first day after head injury. The ischemic burden represented by this “traumatic penumbra” is poorly detected by bedside clinical monitors and has significant associations with outcome.

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