Traumatic brain injury(TBI) at a young age can lead to the development of long-term functional impairments. Severity of injury is well demonstrated to have a strong influence on the extent of functional impairments;ho...Traumatic brain injury(TBI) at a young age can lead to the development of long-term functional impairments. Severity of injury is well demonstrated to have a strong influence on the extent of functional impairments;however, identification of specific magnetic resonance imaging(MRI) biomarkers that are most reflective of injury severity and functional prognosis remain elusive. Therefore, the objective of this study was to utilize advanced statistical approaches to identify clinically relevant MRI biomarkers and predict functional outcomes using MRI metrics in a translational large animal piglet TBI model. TBI was induced via controlled cortical impact and multiparametric MRI was performed at 24 hours and 12 weeks post-TBI using T1-weighted, T2-weighted, T2-weighted fluid attenuated inversion recovery, diffusion-weighted imaging, and diffusion tensor imaging. Changes in spatiotemporal gait parameters were also assessed using an automated gait mat at 24 hours and 12 weeks post-TBI. Principal component analysis was performed to determine the MRI metrics and spatiotemporal gait parameters that explain the largest sources of variation within the datasets. We found that linear combinations of lesion size and midline shift acquired using T2-weighted imaging explained most of the variability of the data at both 24 hours and 12 weeks post-TBI. In addition, linear combinations of velocity, cadence, and stride length were found to explain most of the gait data variability at 24 hours and 12 weeks post-TBI. Linear regression analysis was performed to determine if MRI metrics are predictive of changes in gait. We found that both lesion size and midline shift are significantly correlated with decreases in stride and step length. These results from this study provide an important first step at identifying relevant MRI and functional biomarkers that are predictive of functional outcomes in a clinically relevant piglet TBI model. This study was approved by the University of Georgia Institutional Animal Care and Use Committee(AUP: 展开更多
Traumatic brain injury(TBI)is a major cause of mortality and morbidity in the pediatric population.With advances in medical care,the mortality rate of pediatric TBI has declined.However,more children and adolescents a...Traumatic brain injury(TBI)is a major cause of mortality and morbidity in the pediatric population.With advances in medical care,the mortality rate of pediatric TBI has declined.However,more children and adolescents are living with TBI-related cognitive and emotional impairments,which negatively affects the quality of their life.Adult hippocampal neurogenesis plays an important role in cognition and mood regulation.Alterations in adult hippocampal neurogenesis are associated with a variety of neurological and neurodegenerative diseases,including TBI.Promoting endogenous hippocampal neurogenesis after TBI merits significant attention.However,TBI affects the function of neural stem/progenitor cells in the dentate gyrus of hippocampus,which results in aberrant migration and impaired dendrite development of adult-born neurons.Therefore,a better understanding of adult hippocampal neurogenesis after TBI can facilitate a more successful neuro-restoration of damage in immature brains.Secondary injuries,such as neuroinflammation and oxidative stress,exert a significant impact on hippocampal neurogenesis.Currently,a variety of therapeutic approaches have been proposed for ameliorating secondary TBI injuries.In this review,we discuss the uniqueness of pediatric TBI,adult hippocampal neurogenesis after pediatric TBI,and current efforts that promote neuroprotection to the developing brains,which can be leveraged to facilitate neuroregeneration.展开更多
Background:The pathophysiology of lethal head trauma in infants and young children involves repetitive rotational forces of sufficient magnitude to produce subdural hemorrhage and brain swelling,which leads to conside...Background:The pathophysiology of lethal head trauma in infants and young children involves repetitive rotational forces of sufficient magnitude to produce subdural hemorrhage and brain swelling,which leads to considerable morbidity and mortality.The precise mechanism for brain swelling is unclear.Materials and Methods:We examined cerebral tissue from ten pediatric deaths due to blunt force trauma,along with seven control infants who asphyxiated in unsafe sleep environments.To assess the competence of the blood-brain barrier,we performed immunohistochemical stains for albumin and immunoglobulin G(IgG).Results:IgG and albumin were increased in subpial and superficial perivascular tissue in those cases due to blunt force trauma,and in particular,the blunt force trauma associated with subdural hematoma.This included two deaths at the scene without hospital survival time.Conclusions:Our findings suggest disruption of the blood-brain barrier with vasogenic edema as an early event in head trauma involving young children upstream of global ischemic brain injury.We hypothesize that mechanical injury to the cortical vasculature results in vasogenic edema by oncotic(increased plasma proteins in the cortical interstitium)and hydrostatic(increased capillary pressure)mechanisms,with subsequent cortical ischemia.This may explain why ischemic sequelae appear to occur in head trauma involving young children,regardless of whether anoxia,hypotension,or cardiac arrest complicate the disease course and may in part underlie the high morbidity and mortality of head trauma in early childhood.展开更多
Background:Developing appropriate concussion prevention and management paradigms in middle school(MS)settings requires understanding parents’general levels of concussion-related knowledge and attitudes.This study exa...Background:Developing appropriate concussion prevention and management paradigms in middle school(MS)settings requires understanding parents’general levels of concussion-related knowledge and attitudes.This study examined factors associated with concussion-symptom knowledge and care-seeking attitudes among parents of MS children(aged 10-15 years).Methods:A panel of 1224 randomly selected U.S.residents,aged ≥18 years and identifying as parents of MS children,completed an online questionnaire capturing parental and child characteristics.The parents’concussion-symptom knowledge was measured using 25 questions,with possible answers being“yes”,“maybe”,and“no”.Correct answers earned 2 points,“maybe”answers earned 1 point,and incorrect answers earned 0 point(range:0-50;higher scores=better knowledge).Concussion care-seeking attitudes were also collected using five 7-point scale items(range:5-35;higher scores=more positive attitudes).Multivariable ordinal logistic regression models identified predictors of higher scores.Models met proportional odds assumptions.Adjusted odds ratios(aORs)with 95%confidence intervals(95%CIs)(excluding 1.00)were deemed statistically significant.Results:Median scores were 39(interquartile range:32-44)for symptom knowledge and 32(interquartile range:28-35)for care-seeking attitude.In multivariable models,odds of better symptom knowledge were higher in women vs.men(aOR=2.28;95%CI:1.71-3.05),white/non-Hispanics vs.other racial or ethnic groups(aOR=1.88;95%CI:1.42-2.49),higher parental age(10-year-increase aOR=1.47;95%CI:1.26-1.71),and greater competitiveness(10%-scale-increase aOR=1.24;95%CI:1.13-1.36).Odds of more positive care-seeking attitudes were higher in white/non-Hispanics vs.other racial or ethnic groups(aOR=1.45;95%CI:1.06-1.99)and in older parental age(10-year-increase aOR=1.24;95%CI:1.05-1.47).Conclusion:Characteristics of middle school children’s parents(e.g.,sex,race or ethnicity,age)are associated with their concussion-symptom knowledge and care-seeking att展开更多
基金Financial support was provided by the University of Georgia Office of the Vice President for Research to FDW。
文摘Traumatic brain injury(TBI) at a young age can lead to the development of long-term functional impairments. Severity of injury is well demonstrated to have a strong influence on the extent of functional impairments;however, identification of specific magnetic resonance imaging(MRI) biomarkers that are most reflective of injury severity and functional prognosis remain elusive. Therefore, the objective of this study was to utilize advanced statistical approaches to identify clinically relevant MRI biomarkers and predict functional outcomes using MRI metrics in a translational large animal piglet TBI model. TBI was induced via controlled cortical impact and multiparametric MRI was performed at 24 hours and 12 weeks post-TBI using T1-weighted, T2-weighted, T2-weighted fluid attenuated inversion recovery, diffusion-weighted imaging, and diffusion tensor imaging. Changes in spatiotemporal gait parameters were also assessed using an automated gait mat at 24 hours and 12 weeks post-TBI. Principal component analysis was performed to determine the MRI metrics and spatiotemporal gait parameters that explain the largest sources of variation within the datasets. We found that linear combinations of lesion size and midline shift acquired using T2-weighted imaging explained most of the variability of the data at both 24 hours and 12 weeks post-TBI. In addition, linear combinations of velocity, cadence, and stride length were found to explain most of the gait data variability at 24 hours and 12 weeks post-TBI. Linear regression analysis was performed to determine if MRI metrics are predictive of changes in gait. We found that both lesion size and midline shift are significantly correlated with decreases in stride and step length. These results from this study provide an important first step at identifying relevant MRI and functional biomarkers that are predictive of functional outcomes in a clinically relevant piglet TBI model. This study was approved by the University of Georgia Institutional Animal Care and Use Committee(AUP:
基金This work was supported by the Startup Grant for ZZ from the Department of Natural Sciences,University of Michigan-Dearborn and“CASL Faculty Summer Research Grant”for ZZ from Office of Research&Sponsored Programs,University of Michigan-Dearborn.
文摘Traumatic brain injury(TBI)is a major cause of mortality and morbidity in the pediatric population.With advances in medical care,the mortality rate of pediatric TBI has declined.However,more children and adolescents are living with TBI-related cognitive and emotional impairments,which negatively affects the quality of their life.Adult hippocampal neurogenesis plays an important role in cognition and mood regulation.Alterations in adult hippocampal neurogenesis are associated with a variety of neurological and neurodegenerative diseases,including TBI.Promoting endogenous hippocampal neurogenesis after TBI merits significant attention.However,TBI affects the function of neural stem/progenitor cells in the dentate gyrus of hippocampus,which results in aberrant migration and impaired dendrite development of adult-born neurons.Therefore,a better understanding of adult hippocampal neurogenesis after TBI can facilitate a more successful neuro-restoration of damage in immature brains.Secondary injuries,such as neuroinflammation and oxidative stress,exert a significant impact on hippocampal neurogenesis.Currently,a variety of therapeutic approaches have been proposed for ameliorating secondary TBI injuries.In this review,we discuss the uniqueness of pediatric TBI,adult hippocampal neurogenesis after pediatric TBI,and current efforts that promote neuroprotection to the developing brains,which can be leveraged to facilitate neuroregeneration.
文摘Background:The pathophysiology of lethal head trauma in infants and young children involves repetitive rotational forces of sufficient magnitude to produce subdural hemorrhage and brain swelling,which leads to considerable morbidity and mortality.The precise mechanism for brain swelling is unclear.Materials and Methods:We examined cerebral tissue from ten pediatric deaths due to blunt force trauma,along with seven control infants who asphyxiated in unsafe sleep environments.To assess the competence of the blood-brain barrier,we performed immunohistochemical stains for albumin and immunoglobulin G(IgG).Results:IgG and albumin were increased in subpial and superficial perivascular tissue in those cases due to blunt force trauma,and in particular,the blunt force trauma associated with subdural hematoma.This included two deaths at the scene without hospital survival time.Conclusions:Our findings suggest disruption of the blood-brain barrier with vasogenic edema as an early event in head trauma involving young children upstream of global ischemic brain injury.We hypothesize that mechanical injury to the cortical vasculature results in vasogenic edema by oncotic(increased plasma proteins in the cortical interstitium)and hydrostatic(increased capillary pressure)mechanisms,with subsequent cortical ischemia.This may explain why ischemic sequelae appear to occur in head trauma involving young children,regardless of whether anoxia,hypotension,or cardiac arrest complicate the disease course and may in part underlie the high morbidity and mortality of head trauma in early childhood.
基金the Division of Unintentional Injury,Centers for Disease Control and Prevention(5U01CE002885-02)The University of North Carolina Injury Prevention Research Center is also partly supported by an Injury Control Research Center award(R49/CE002479)from the National Center for Injury Prevention and Control,Centers for Disease Control and Prevention.
文摘Background:Developing appropriate concussion prevention and management paradigms in middle school(MS)settings requires understanding parents’general levels of concussion-related knowledge and attitudes.This study examined factors associated with concussion-symptom knowledge and care-seeking attitudes among parents of MS children(aged 10-15 years).Methods:A panel of 1224 randomly selected U.S.residents,aged ≥18 years and identifying as parents of MS children,completed an online questionnaire capturing parental and child characteristics.The parents’concussion-symptom knowledge was measured using 25 questions,with possible answers being“yes”,“maybe”,and“no”.Correct answers earned 2 points,“maybe”answers earned 1 point,and incorrect answers earned 0 point(range:0-50;higher scores=better knowledge).Concussion care-seeking attitudes were also collected using five 7-point scale items(range:5-35;higher scores=more positive attitudes).Multivariable ordinal logistic regression models identified predictors of higher scores.Models met proportional odds assumptions.Adjusted odds ratios(aORs)with 95%confidence intervals(95%CIs)(excluding 1.00)were deemed statistically significant.Results:Median scores were 39(interquartile range:32-44)for symptom knowledge and 32(interquartile range:28-35)for care-seeking attitude.In multivariable models,odds of better symptom knowledge were higher in women vs.men(aOR=2.28;95%CI:1.71-3.05),white/non-Hispanics vs.other racial or ethnic groups(aOR=1.88;95%CI:1.42-2.49),higher parental age(10-year-increase aOR=1.47;95%CI:1.26-1.71),and greater competitiveness(10%-scale-increase aOR=1.24;95%CI:1.13-1.36).Odds of more positive care-seeking attitudes were higher in white/non-Hispanics vs.other racial or ethnic groups(aOR=1.45;95%CI:1.06-1.99)and in older parental age(10-year-increase aOR=1.24;95%CI:1.05-1.47).Conclusion:Characteristics of middle school children’s parents(e.g.,sex,race or ethnicity,age)are associated with their concussion-symptom knowledge and care-seeking att
