Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological d...Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological disorders has increased considerably over the past 30 years because of population aging.Overall,neurological diseases significantly impair cognitive and motor functions and their incidence will increase as societies age and the world's population continues to grow.Autism spectrum disorder,motor neuron disease,encephalopathy,epilepsy,stroke,ataxia,Alzheimer's disease,amyotrophic lateral sclerosis,Huntington's disease,and Parkinson's disease represent a non-exhaustive list of neurological illnesses.These affections are due to perturbations in cellular homeostasis leading to the progressive injury and death of neurons in the nervous system.Among the common features of neurological handicaps,we find protein aggregation,oxidative stress,neuroinflammation,and mitochondrial impairment in the target tissues,e.g.,the brain,cerebellum,and spinal cord.The high energy requirements of neurons and their inability to produce sufficient adenosine triphosphate by glycolysis,are responsible for their dependence on functional mitochondria for their integrity.Reactive oxygen species,produced along with the respiration process within mitochondria,can lead to oxidative stress,which compromises neuronal survival.Besides having an essential role in energy production and oxidative stress,mitochondria are indispensable for an array of cellular processes,such as amino acid metabolism,iron-sulfur cluster biosynthesis,calcium homeostasis,intrinsic programmed cell death(apoptosis),and intraorganellar signaling.Despite the progress made in the last decades in the understanding of a growing number of genetic and molecular causes of central nervous diseases,therapies that are effective to diminish or halt neuronal dysfunction/death are rare.Given the genetic complexity responsible for neurological disorders,the development of neuroprotective strategies seeking to preserve mitochondrial homeostasis is a realistic challenge to lastingly diminish the harmful evolution of these pathologies and so to recover quality of life.A promising candidate is the neuroglobin,a globin superfamily member of 151 amino acids,which is found at high levels in the brain,the eye,and the cerebellum.The protein,which localizes to mitochondria,is involved in electron transfer,oxygen storage and defence against oxidative stress;hence,possessing neuroprotective properties.This review surveys up-to-date knowledge and emphasizes on existing investigations regarding neuroglobin physiological functions,which remain since its discovery in 2000 under intense debate and the possibility of using neuroglobin either by gene therapy or its direct delivery into the brain to treat neurological disorders.展开更多
Despite the existence of treatment for diabetes,inadequate metabolic control triggers the appearance of chronic complications such as diabetic retinopathy.Diabetic retinopathy is considered a multifactorial disease of...Despite the existence of treatment for diabetes,inadequate metabolic control triggers the appearance of chronic complications such as diabetic retinopathy.Diabetic retinopathy is considered a multifactorial disease of complex etiology in which oxidative stress and low chronic inflammation play essential roles.Chronic exposure to hyperglycemia triggers a loss of redox balance that is critical for the appearance of neuronal and vascular damage during the development and progression of the disease.Current therapies for the treatment of diabetic retinopathy are used in advanced stages of the disease and are unable to reverse the retinal damage induced by hyperglycemia.The lack of effective therapies without side effects means there is an urgent need to identify an early action capable of preventing the development of the disease and its pathophysiological consequences in order to avoid loss of vision associated with diabetic retinopathy.Therefore,in this review we propose different therapeutic targets related to the modulation of the redox and inflammatory status that,potentially,can prevent the development and progression of the disease.展开更多
Objective Previous outcome reports of congenital diaphragmatic hernia(CDH)have described neuroimaging anomalies and neurodevelopmental impairment.However,the link between imaging and outcome has not been described.We ...Objective Previous outcome reports of congenital diaphragmatic hernia(CDH)have described neuroimaging anomalies and neurodevelopmental impairment.However,the link between imaging and outcome has not been described.We aimed to determine whether routine postoperative neonatal neuroimaging in infants with CDH detects later neurodevelopmental impairment.Methods In a prospective cohort study within a clinical service in The Royal Children’s Hospital Newborn Intensive Care.Cerebral ultrasound was performed in 81 children and MRI in 57 children who subsequently underwent neurodevelopmental follow-up after surgery for CDH.MRI scans were analyzed using a scoring system designed to identify injury,maturation and volume loss.Neurodevelopmental assessment occurred at 2 years(48)and neurocognitive assessment at 5 years(26)and/or 8 years(27).Brain imaging scores corrected for gestational age at scan time were correlated with outcome measures,adjusting for known clinical confounders.results Clinically significant findings were identified on MRI of 16(28%)infants.Mean scores were in the normal range for all domains assessed at each age.Language impairment was seen in 23%at 2 years and verbal intellectual impairment in 25%at 8 years.Mean cognitive scores were lower in 2-year-old children with white matter injury on MRI(p=0.03).Mean motor scores were lower in 2-year-old children with brain immaturity(p=0.01).Associations between MRI and 5-year and 8-year assessments were no longer significant when adjusting for known clinical confounders.Conclusions Neuroimaging abnormalities were associated with worse neurodevelopment at 2 years,but not with later neurocognitive outcomes,after accounting for clinical risk factors.展开更多
Extreme preterm infants(<28 weeks'gestation)often require positive pressure ventilation with oxygen during postnatal stabilization in the delivery room.To date,optimal inspired fraction of oxygen(FiO_(2))still ...Extreme preterm infants(<28 weeks'gestation)often require positive pressure ventilation with oxygen during postnatal stabilization in the delivery room.To date,optimal inspired fraction of oxygen(FiO_(2))still represents a conundrum in newborn care oscillating between higher(>60%)and lower(<30%)initial FiO_(2).Recent evidence and meta-analyses have underscored the predictive value for survival and/or relevant clinical outcomes of the Apgar score and the achievement of arterial oxygen saturation measured by pulse oximetry≥85%at 5 minutes after birth.New clinical trials comparing higher versus lower initial FiO_(2)have been launched aiming to optimize postnatal stabilization of extreme preterm while avoiding adverse effects of hypoxemia or hyperoxemia.展开更多
基金supported by AFM-Telethon grants N°21704 and 23264,Universite Paris Cite(Paris)the National Institute of Health and Medical Research(INSERM)+3 种基金the National Center for Scientific Research(CNRS)the French Association Connaître les Syndromes Cerebelleux(CSC)(to MCD)GV/2021/188 granted from Conselleria of Innovation,Universities,28 Science and Society digital of the Community of Valencia(Spain)(to ITC)Subprograma Atraccion de Talento-Contratos Postdoctorales de la Universitat de Valencia(to IMY).
文摘Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological disorders has increased considerably over the past 30 years because of population aging.Overall,neurological diseases significantly impair cognitive and motor functions and their incidence will increase as societies age and the world's population continues to grow.Autism spectrum disorder,motor neuron disease,encephalopathy,epilepsy,stroke,ataxia,Alzheimer's disease,amyotrophic lateral sclerosis,Huntington's disease,and Parkinson's disease represent a non-exhaustive list of neurological illnesses.These affections are due to perturbations in cellular homeostasis leading to the progressive injury and death of neurons in the nervous system.Among the common features of neurological handicaps,we find protein aggregation,oxidative stress,neuroinflammation,and mitochondrial impairment in the target tissues,e.g.,the brain,cerebellum,and spinal cord.The high energy requirements of neurons and their inability to produce sufficient adenosine triphosphate by glycolysis,are responsible for their dependence on functional mitochondria for their integrity.Reactive oxygen species,produced along with the respiration process within mitochondria,can lead to oxidative stress,which compromises neuronal survival.Besides having an essential role in energy production and oxidative stress,mitochondria are indispensable for an array of cellular processes,such as amino acid metabolism,iron-sulfur cluster biosynthesis,calcium homeostasis,intrinsic programmed cell death(apoptosis),and intraorganellar signaling.Despite the progress made in the last decades in the understanding of a growing number of genetic and molecular causes of central nervous diseases,therapies that are effective to diminish or halt neuronal dysfunction/death are rare.Given the genetic complexity responsible for neurological disorders,the development of neuroprotective strategies seeking to preserve mitochondrial homeostasis is a realistic challenge to lastingly diminish the harmful evolution of these pathologies and so to recover quality of life.A promising candidate is the neuroglobin,a globin superfamily member of 151 amino acids,which is found at high levels in the brain,the eye,and the cerebellum.The protein,which localizes to mitochondria,is involved in electron transfer,oxygen storage and defence against oxidative stress;hence,possessing neuroprotective properties.This review surveys up-to-date knowledge and emphasizes on existing investigations regarding neuroglobin physiological functions,which remain since its discovery in 2000 under intense debate and the possibility of using neuroglobin either by gene therapy or its direct delivery into the brain to treat neurological disorders.
文摘Despite the existence of treatment for diabetes,inadequate metabolic control triggers the appearance of chronic complications such as diabetic retinopathy.Diabetic retinopathy is considered a multifactorial disease of complex etiology in which oxidative stress and low chronic inflammation play essential roles.Chronic exposure to hyperglycemia triggers a loss of redox balance that is critical for the appearance of neuronal and vascular damage during the development and progression of the disease.Current therapies for the treatment of diabetic retinopathy are used in advanced stages of the disease and are unable to reverse the retinal damage induced by hyperglycemia.The lack of effective therapies without side effects means there is an urgent need to identify an early action capable of preventing the development of the disease and its pathophysiological consequences in order to avoid loss of vision associated with diabetic retinopathy.Therefore,in this review we propose different therapeutic targets related to the modulation of the redox and inflammatory status that,potentially,can prevent the development and progression of the disease.
文摘Objective Previous outcome reports of congenital diaphragmatic hernia(CDH)have described neuroimaging anomalies and neurodevelopmental impairment.However,the link between imaging and outcome has not been described.We aimed to determine whether routine postoperative neonatal neuroimaging in infants with CDH detects later neurodevelopmental impairment.Methods In a prospective cohort study within a clinical service in The Royal Children’s Hospital Newborn Intensive Care.Cerebral ultrasound was performed in 81 children and MRI in 57 children who subsequently underwent neurodevelopmental follow-up after surgery for CDH.MRI scans were analyzed using a scoring system designed to identify injury,maturation and volume loss.Neurodevelopmental assessment occurred at 2 years(48)and neurocognitive assessment at 5 years(26)and/or 8 years(27).Brain imaging scores corrected for gestational age at scan time were correlated with outcome measures,adjusting for known clinical confounders.results Clinically significant findings were identified on MRI of 16(28%)infants.Mean scores were in the normal range for all domains assessed at each age.Language impairment was seen in 23%at 2 years and verbal intellectual impairment in 25%at 8 years.Mean cognitive scores were lower in 2-year-old children with white matter injury on MRI(p=0.03).Mean motor scores were lower in 2-year-old children with brain immaturity(p=0.01).Associations between MRI and 5-year and 8-year assessments were no longer significant when adjusting for known clinical confounders.Conclusions Neuroimaging abnormalities were associated with worse neurodevelopment at 2 years,but not with later neurocognitive outcomes,after accounting for clinical risk factors.
基金L.T.-R.enjoys a“Post-MIR”predoctoral research grant from the Health Research Institute La Fe(IISLAFE).I.L.-C.and A.P.-G.enjoy Rio Hortega predoctoral grants from the Instituto de Investigación en Salud Carlos III(Ministry of Science,Spain).
文摘Extreme preterm infants(<28 weeks'gestation)often require positive pressure ventilation with oxygen during postnatal stabilization in the delivery room.To date,optimal inspired fraction of oxygen(FiO_(2))still represents a conundrum in newborn care oscillating between higher(>60%)and lower(<30%)initial FiO_(2).Recent evidence and meta-analyses have underscored the predictive value for survival and/or relevant clinical outcomes of the Apgar score and the achievement of arterial oxygen saturation measured by pulse oximetry≥85%at 5 minutes after birth.New clinical trials comparing higher versus lower initial FiO_(2)have been launched aiming to optimize postnatal stabilization of extreme preterm while avoiding adverse effects of hypoxemia or hyperoxemia.
