Traumatic brain injury is a major cause of death and disability worldwide,affecting over 69 million individuals yearly.One-carbon metabolism has been shown to have beneficial effects after brain damage,such as ischemi...Traumatic brain injury is a major cause of death and disability worldwide,affecting over 69 million individuals yearly.One-carbon metabolism has been shown to have beneficial effects after brain damage,such as ischemic stroke.However,whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more investigation.The aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain injury.PubMed,Web of Science,and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury outcomes.The search terms included combinations of the following words:traumatic brain injury,dietary supplementation,one-carbon metabolism,and B-vitamins.The focus of each literature search was basic science data.The year of publication in the literature searches was not limited.Our analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recove ry of animals with traumatic brain injury compared to controls.Howeve r,this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delive ry of vitamin supplementation post-traumatic brain injury.The details of supplementation post-traumatic brain injury need to be further investigated.Overall,we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model systems.Further investigation in a clinical setting should be stro ngly considered in co njunction with current medical treatments for traumatic brain injury-affected individuals.展开更多
Maternal one-carbon metabolism plays an important role in early life programming.There is a well-established connection between the fetal environment and the health status of the offspring.Howeve r,there is a knowledg...Maternal one-carbon metabolism plays an important role in early life programming.There is a well-established connection between the fetal environment and the health status of the offspring.Howeve r,there is a knowledge gap on how maternal nutrition impacts stro ke outcomes in offspring.The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcomes in 3-month-old offspring.Adult female mice were fed a folic acid-deficient diet,choline-deficient diet,or control diet 4 weeks before pregnancy.They we re continued on diets during pregnancy and la ctation.Male and female offspring were weaned onto a control diet and at 2 months of age were subjected to ischemic stroke within the sensorimotor cortex via photothrombotic damage.Mothers maintained on either a folic acid-deficient diet or choline-deficient diet had reduced levels of S-adenosylm ethionine in the liver and S-adenosylhomocysteine in the plasma.After ischemic stro ke,motor function was impaired in 3-month-old offspring from mothers receiving either a folic acid-deficient diet or choline-deficient diet compared to the animals receiving a control diet.In brain tissue,there was no difference in ischemic damage volume.When protein levels were assessed in ischemic brain tissue,there were lower levels of active caspase-3 and hypoxia-inducible factor 1α in males compared to females and betaine levels were reduced in offspring from the mothers receiving a choline-deficient diet.Our results demonstrate that a deficient maternal diet at critical time points in neurodevelopment results in worse stro ke outcomes.This study emphasizes the importance of maternal diet and the impact it can have on offspring health.展开更多
Currently,ischemic stroke is the most prevalent form of stroke compared to hemorrhagic and there is a high incidence in older adults.Nutrition is a modifiable risk factor for stroke.B-vitamins are part of a metabolic ...Currently,ischemic stroke is the most prevalent form of stroke compared to hemorrhagic and there is a high incidence in older adults.Nutrition is a modifiable risk factor for stroke.B-vitamins are part of a metabolic network that integrates nutritional signals with biosynthesis,redox homeostasis,and epigenetics.These vitamins play an essential role in the regulation of cell proliferation,stress resistance,and embryo development.A deficiency in vitamin B12 is common in older adults and has been reported to be implicated in ischemic stroke.The aim of this review was to investigate whether vitamin B12 deficiencies impact the risk and outcome of ischemic stroke.Clinical data from our literature review strongly suggest that a deficiency in vitamin B12 is a risk factor for ischemic stroke and possible outcome.Our survey of the literature has identified that there is a gap in the understanding of the mechanisms through which a vitamin B12 deficiency leads to an increased risk of stroke and outcome.A vitamin B12 deficiency can increase homocysteine levels,which are a well-established risk factor for ischemic stroke.Another potential mechanism through which vitamin B12 deficient may impact neurological function and increase risk of stroke,is changes in myelination,however this link requires further investigation.Further studies are required in model systems to understand how a vitamin B12 deficiency changes the brain.展开更多
Stroke is the leading cause of long-term disability worldwide.There are two main types of stroke,hemorrhagic and ischemic.A hemorrhagic stroke is when there a bleed in the brain,whereas an ischemic stroke is the resul...Stroke is the leading cause of long-term disability worldwide.There are two main types of stroke,hemorrhagic and ischemic.A hemorrhagic stroke is when there a bleed in the brain,whereas an ischemic stroke is the result of blockage of blood flow to the brain,which leads to degeneration,neurotoxicity,inflammation,and apoptosis.This damage not only affects the ischemic core,but also neuronal,astrocyte,and synaptic survival in the peri-infarct region and connected areas(Kerr et al.,2011;Jadavji et al.,2018).The prevalence of ischemic stroke is predicted to increase as the global population ages(Mukherjee and Patil,2011).Between 1970 and 2008 there has been a 100%increase in stroke incidence in low income countries.For example,the estimated losses in gross domestic product,as the result of vascular diseases,including stroke,have ranged from$20 million in Ethiopia to$1 billion in China and India(Mukherjee and Patil,2011).展开更多
Tissue plasminogen activator (tPA) use in the treatment of isch- emic stroke: tPA is a serine protease that catalyzes the breakdown of blood dots. Because of its thrombolytic properties, tPA is used to treat specif...Tissue plasminogen activator (tPA) use in the treatment of isch- emic stroke: tPA is a serine protease that catalyzes the breakdown of blood dots. Because of its thrombolytic properties, tPA is used to treat specific types of stroke, including ischemia, but is contra- indicated for treatment of hemorrhagic stroke or head trauma. Although a life saving and powerful 'dot buster', tPA has a short therapeutic window. When administered outside of this prescribed timeframe, research suggests that tPA can produce neurotoxic ef- fects in the brain, due in part to activation of several signalling pro- cesses associated with cell apoptosis, degradation of the extracel- lular matrix, and increase in the permeability of the neurovascular unit (Yepes et al., 2009). Concerted research has been dedicated to- ward understanding the mechanisms mediating the impact of tPA on the brain, using both in vivo and in vitro animal models.展开更多
In the cell,one-carbon metabolism modulates nucleotide synthesis,DNA repair,as well as methylation through the reduction of homocysteine(Figure 1).High levels of plasma homocysteine have been associated with negativ...In the cell,one-carbon metabolism modulates nucleotide synthesis,DNA repair,as well as methylation through the reduction of homocysteine(Figure 1).High levels of plasma homocysteine have been associated with negative health outcomes in humans(Murray et al.,2017).Folates,B-vitamins,are a major component of one-carbon metabolism and play an important role in brain function.Specifically,they are involved in nucleotide synthesis,DNA repair,methylation,second messenger systems,ion channels,protein,展开更多
Traditionally,it has been thought that the mammalian central nervous system(CNS)does not regenerate.Possibly due to the inhibitory extracellular environment post-injury as well as the limited intrinsic characteristi...Traditionally,it has been thought that the mammalian central nervous system(CNS)does not regenerate.Possibly due to the inhibitory extracellular environment post-injury as well as the limited intrinsic characteristics of adult post-mitotic neurons(Smith et al.,2015).展开更多
基金Salary for TCT was supported by National Institutes of Health Grant(R01NS100793)。
文摘Traumatic brain injury is a major cause of death and disability worldwide,affecting over 69 million individuals yearly.One-carbon metabolism has been shown to have beneficial effects after brain damage,such as ischemic stroke.However,whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more investigation.The aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain injury.PubMed,Web of Science,and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury outcomes.The search terms included combinations of the following words:traumatic brain injury,dietary supplementation,one-carbon metabolism,and B-vitamins.The focus of each literature search was basic science data.The year of publication in the literature searches was not limited.Our analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recove ry of animals with traumatic brain injury compared to controls.Howeve r,this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delive ry of vitamin supplementation post-traumatic brain injury.The details of supplementation post-traumatic brain injury need to be further investigated.Overall,we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model systems.Further investigation in a clinical setting should be stro ngly considered in co njunction with current medical treatments for traumatic brain injury-affected individuals.
文摘Maternal one-carbon metabolism plays an important role in early life programming.There is a well-established connection between the fetal environment and the health status of the offspring.Howeve r,there is a knowledge gap on how maternal nutrition impacts stro ke outcomes in offspring.The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcomes in 3-month-old offspring.Adult female mice were fed a folic acid-deficient diet,choline-deficient diet,or control diet 4 weeks before pregnancy.They we re continued on diets during pregnancy and la ctation.Male and female offspring were weaned onto a control diet and at 2 months of age were subjected to ischemic stroke within the sensorimotor cortex via photothrombotic damage.Mothers maintained on either a folic acid-deficient diet or choline-deficient diet had reduced levels of S-adenosylm ethionine in the liver and S-adenosylhomocysteine in the plasma.After ischemic stro ke,motor function was impaired in 3-month-old offspring from mothers receiving either a folic acid-deficient diet or choline-deficient diet compared to the animals receiving a control diet.In brain tissue,there was no difference in ischemic damage volume.When protein levels were assessed in ischemic brain tissue,there were lower levels of active caspase-3 and hypoxia-inducible factor 1α in males compared to females and betaine levels were reduced in offspring from the mothers receiving a choline-deficient diet.Our results demonstrate that a deficient maternal diet at critical time points in neurodevelopment results in worse stro ke outcomes.This study emphasizes the importance of maternal diet and the impact it can have on offspring health.
基金supported by Midwestern University Startup Funds(to NMJ)American Heart Association,No.20AIREA35050015(to NMJ)。
文摘Currently,ischemic stroke is the most prevalent form of stroke compared to hemorrhagic and there is a high incidence in older adults.Nutrition is a modifiable risk factor for stroke.B-vitamins are part of a metabolic network that integrates nutritional signals with biosynthesis,redox homeostasis,and epigenetics.These vitamins play an essential role in the regulation of cell proliferation,stress resistance,and embryo development.A deficiency in vitamin B12 is common in older adults and has been reported to be implicated in ischemic stroke.The aim of this review was to investigate whether vitamin B12 deficiencies impact the risk and outcome of ischemic stroke.Clinical data from our literature review strongly suggest that a deficiency in vitamin B12 is a risk factor for ischemic stroke and possible outcome.Our survey of the literature has identified that there is a gap in the understanding of the mechanisms through which a vitamin B12 deficiency leads to an increased risk of stroke and outcome.A vitamin B12 deficiency can increase homocysteine levels,which are a well-established risk factor for ischemic stroke.Another potential mechanism through which vitamin B12 deficient may impact neurological function and increase risk of stroke,is changes in myelination,however this link requires further investigation.Further studies are required in model systems to understand how a vitamin B12 deficiency changes the brain.
基金funded by the Natural Sciences and Engineering Research Council(NSERC)Canada(to NMJ)
文摘Stroke is the leading cause of long-term disability worldwide.There are two main types of stroke,hemorrhagic and ischemic.A hemorrhagic stroke is when there a bleed in the brain,whereas an ischemic stroke is the result of blockage of blood flow to the brain,which leads to degeneration,neurotoxicity,inflammation,and apoptosis.This damage not only affects the ischemic core,but also neuronal,astrocyte,and synaptic survival in the peri-infarct region and connected areas(Kerr et al.,2011;Jadavji et al.,2018).The prevalence of ischemic stroke is predicted to increase as the global population ages(Mukherjee and Patil,2011).Between 1970 and 2008 there has been a 100%increase in stroke incidence in low income countries.For example,the estimated losses in gross domestic product,as the result of vascular diseases,including stroke,have ranged from$20 million in Ethiopia to$1 billion in China and India(Mukherjee and Patil,2011).
文摘Tissue plasminogen activator (tPA) use in the treatment of isch- emic stroke: tPA is a serine protease that catalyzes the breakdown of blood dots. Because of its thrombolytic properties, tPA is used to treat specific types of stroke, including ischemia, but is contra- indicated for treatment of hemorrhagic stroke or head trauma. Although a life saving and powerful 'dot buster', tPA has a short therapeutic window. When administered outside of this prescribed timeframe, research suggests that tPA can produce neurotoxic ef- fects in the brain, due in part to activation of several signalling pro- cesses associated with cell apoptosis, degradation of the extracel- lular matrix, and increase in the permeability of the neurovascular unit (Yepes et al., 2009). Concerted research has been dedicated to- ward understanding the mechanisms mediating the impact of tPA on the brain, using both in vivo and in vitro animal models.
基金funded by Graduate Award for Ontario Students for Research in Dementiafunded by Canadian Institutes of Health Research(CIHR)Studentshipfunded by the Natural Sciences and Engineering Research Council(NSERC) grant
文摘In the cell,one-carbon metabolism modulates nucleotide synthesis,DNA repair,as well as methylation through the reduction of homocysteine(Figure 1).High levels of plasma homocysteine have been associated with negative health outcomes in humans(Murray et al.,2017).Folates,B-vitamins,are a major component of one-carbon metabolism and play an important role in brain function.Specifically,they are involved in nucleotide synthesis,DNA repair,methylation,second messenger systems,ion channels,protein,
文摘Traditionally,it has been thought that the mammalian central nervous system(CNS)does not regenerate.Possibly due to the inhibitory extracellular environment post-injury as well as the limited intrinsic characteristics of adult post-mitotic neurons(Smith et al.,2015).