Corrigendum to "Pediatric Traumatic Brain Injury and Autism: Elucidating Shared Mechanisms".
Ontology highlight
ABSTRACT:
SUBMITTER: Singh R
PROVIDER: S-EPMC5534305 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:Pediatric traumatic brain injury (TBI) is a significant problem of public health importance worldwide. Large population-based studies on the effect of birth order on health phenomena are exceedingly rare. This study examines the relationship between birth order and risk for pediatric TBI among sibling groups. We performed a retrospective cohort study following 59,469 Finnish newborns from 1987 until age 18 years. Data on first diagnosis of TBI was recorded within the 1987 Finnish Birth Cohort (FBC). Compared with first born siblings, later born siblings had an increased risk of TBI during the follow-up period (hazard ratio [HR] 1.02; 95% confidence interval [CI] 0.91-1.14 for second born, HR 1.09; 95% CI 0.95 1.26 for third born, HR 1.28; 95% CI 1.08-1.53 for fourth or higher). When adjusted for sex and maternal age at child's birth, HRs (95% CIs) for TBI during the follow-up period were 1.12 (0.99-1.26) for second born, 1.31 (1.12-1.53) for third born and 1.61 (1.33-1.95) for fourth born or higher children, respectively. Within this large register-based population-wide study, order of birth modified risk for pediatric TBI among sibling groups. Taken together, these study findings may serve to stimulate further inquiry into genetic, psychological, or psychosocial factors which underlie differences in risk and depth of effect within and between sibling groups.
| S-EPMC9402548 | biostudies-literature
Project description:To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric traumatic brain injury.National Library of Medicine PubMed literature review.The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of traumatic brain injury is summarized. Unique features of the developing brain that could either enhance or limit the efficacy of neuroprotection by progesterone are discussed, and the limited preclinical literature using progesterone after acute injury to the developing brain is described. Finally, the current status of clinical trials of progesterone for adult traumatic brain injury is reviewed.Progesterone is a pleiotropic agent with beneficial effects on secondary injury cascades that occur after traumatic brain injury, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after traumatic brain injury in adult animal models, with results summarized in tabular form. However, very few studies have evaluated progesterone in pediatric animal models of brain injury. To date, two human phase II trials of progesterone for adult traumatic brain injury have been published, and two multicenter phase III trials are underway.The unique features of the developing brain from that of a mature adult brain make it necessary to independently study progesterone in clinically relevant, immature animal models of traumatic brain injury. Additional preclinical studies could lead to the development of a novel neuroprotective therapy that could reduce the long-term disability in head-injured children and could potentially provide benefit in other forms of pediatric brain injury (global ischemia, stroke, and statue epilepticus).
| S-EPMC4806367 | biostudies-literature
Project description:Ventilator-associated pneumonia (VAP) is a common occurrence among intubated pediatric traumatic brain injury (TBI) patients. However, little is known about the epidemiology, risk factors, and microbiology of VAP in pediatric TBI. We reviewed a cohort of 119 pediatric moderate-to-severe TBI patients and identified 42 with VAP by positive protected bronchial brush specimens. Location of intubation, severity of injury, and antibiotic administration within 2 days after injury were not associated with VAP. Most treatments for elevated intracranial pressure were associated with increased risk of VAP; however, in a multi-variable analysis barbiturate coma (hazard ratio [HR], 3.2; 95% confidence interval [CI] 1.4-7.3), neuromuscular blockade (NMBA; HR, 3.4; 95% CI 1.6-7.3), and use of a cooling blanket for euthermia (HR 2.4; 95% CI 1.1-5.5) remained independently associated with VAP. Most VAP (55%) occurred prior to hospital Day 4 and only 7% developed VAP after Day 7. Methicillin-sensitive Staphylococcus aureus (34%), Haemophilus influenzae (22%), and Streptococcus pneumoniae (15%) were the most common organisms, comprising 71% of isolated pathogens (36% of infections were polymicrobial). Patients with VAP had significantly longer intensive care unit and hospital stays, as well as increased risk of chronic care needs after discharge, but not mortality. VAP is a common occurrence in pediatric TBI patients, and early empiric therapy for patients requiring barbiturate infusion, NMBA, or use of a cooling blanket could mitigate morbidity.
| S-EPMC4939445 | biostudies-literature
Project description:Traumatic brain injury (TBI) is a significant public health concern, and can be especially disruptive in children, derailing on-going neuronal maturation in periods critical for cognitive development. There is considerable heterogeneity in post-injury outcomes, only partially explained by injury severity. Understanding the time course of recovery, and what factors may delay or promote recovery, will aid clinicians in decision-making and provide avenues for future mechanism-based therapeutics. We examined regional changes in brain volume in a pediatric/adolescent moderate-severe TBI (msTBI) cohort, assessed at two time points. Children were first assessed 2-5 months post-injury, and again 12 months later. We used tensor-based morphometry (TBM) to localize longitudinal volume expansion and reduction. We studied 21 msTBI patients (5 F, 8-18 years old) and 26 well-matched healthy control children, also assessed twice over the same interval. In a prior paper, we identified a subgroup of msTBI patients, based on interhemispheric transfer time (IHTT), with significant structural disruption of the white matter (WM) at 2-5 months post injury. We investigated how this subgroup (TBI-slow, N = 11) differed in longitudinal regional volume changes from msTBI patients (TBI-normal, N = 10) with normal WM structure and function. The TBI-slow group had longitudinal decreases in brain volume in several WM clusters, including the corpus callosum and hypothalamus, while the TBI-normal group showed increased volume in WM areas. Our results show prolonged atrophy of the WM over the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows a different pattern that could indicate a return to a healthy trajectory.
| S-EPMC5423316 | biostudies-literature
Project description:Traumatic brain injuries (TBIs) account for the majority of injury-related deaths in the United States with roughly two million TBIs occurring annually. Due to the spectrum of severity and heterogeneity in TBIs, investigation into the secondary injury is necessary in order to formulate an effective treatment. A mechanical consequence of trauma involves dysregulation of the blood-brain barrier (BBB) which contributes to secondary injury and exposure of peripheral components to the brain parenchyma. Recent studies have shed light on the mechanisms of BBB breakdown in TBI including novel intracellular signaling and cell-cell interactions within the BBB niche. The current review provides an overview of the BBB, novel detection methods for disruption, and the cellular and molecular mechanisms implicated in regulating its stability following TBI.
| S-EPMC7246537 | biostudies-literature
Project description:The optimal management of severe traumatic brain injury (TBI) in the pediatric population has not been well studied. There are a limited number of research articles studying the management of TBI in children. Given the prevalence of severe TBI in the pediatric population, it is crucial to develop a reference TBI management plan for this vulnerable population. In this review, we seek to delineate the differences between severe TBI management in adults and children. Additionally, we also discuss the known molecular pathogenesis of TBI. A better understanding of the pathophysiology of TBI will inform clinical management and development of therapeutics. Finally, we propose a clinical algorithm for the management and treatment of severe TBI in children using published data.
| S-EPMC9263560 | biostudies-literature
Project description:Traumatic brain injury (TBI) is the leading cause of death and disability among children in the United States. Affected children will often suffer from emotional, cognitive and neurological impairments throughout life. In the controlled cortical impact (CCI) animal model of pediatric TBI (postnatal day 16-17) it was demonstrated that injury results in abnormal neuronal hypoactivity in the non-injured primary somatosensory cortex (S1). It materializes that reshaping the abnormal post-injury neuronal activity may provide a suitable strategy to augment rehabilitation. We tested whether high-frequency, non-invasive transcranial magnetic stimulation (TMS) delivered twice a week over a four-week period can rescue the neuronal activity and improve the long-term functional neurophysiological and behavioral outcome in the pediatric CCI model. The results show that TBI rats subjected to TMS therapy showed significant increases in the evoked-fMRI cortical responses (189%), evoked synaptic activity (46%), evoked neuronal firing (200%) and increases expression of cellular markers of neuroplasticity in the non-injured S1 compared to TBI rats that did not receive therapy. Notably, these rats showed less hyperactivity in behavioral tests. These results implicate TMS as a promising approach for reversing the adverse neuronal mechanisms activated post-TBI. Importantly, this intervention could readily be translated to human studies.
| S-EPMC4594036 | biostudies-other
Project description:Heterogeneity of injury severity among children with traumatic brain injury (TBI) classified by the Glasgow Coma Scale (GCS) makes comparisons across research cohorts, enrollment in clinical trials, and clinical predictions of outcomes difficult. The present study uses latent class analysis (LCA) to distinguish severity subgroups from a prospective cohort of 433 children 2.5-15 years of age with TBI who were recruited from two level 1 pediatric trauma centers. Indicator variables available within 48 h post-injury including emergency department (ED) GCS, hospital motor GCS, Abbreviated Injury Score (AIS), Rotterdam Score, hypotension in the ED, and pre-hospital loss of consciousness, intubation, seizures, and sedation were evaluated to define subgroups. To understand whether latent class subgroups were predictive of clinically meaningful outcomes, the Pediatric Injury Functional Outcome Scale (PIFOS) at 6 and 12 months, and the Behavior Rating Inventory of Executive Function at 12 months, were compared across subgroups. Then, outcomes were examined by GCS (primary) and AIS (secondary) classification alone to assess whether LCA provided improved outcome prediction. LCA identified four distinct increasing severity subgroups (1-4). Unlike GCS classification, mean outcome differences on PIFOS at 6 months showed decreasing function across classes. PIFOS differences relative to the lowest latent class (LC1) were: LC2 2.27 (0.83, 3.72), LC3 3.99 (1.88, 6.10), and LC4 11.2 (7.04, 15.4). Differences in 12 month outcomes were seen between the most and least severely injured groups. Differences in outcomes in relation to AIS were restricted to the most and less severely injured at both time points. This study distinguished four latent classes that are clinically meaningful, distinguished a more homogenous severe injury group, and separated children by 6-month functional outcomes better than GCS alone. Systematic reporting of these variables would allow comparisons across research cohorts, potentially improve clinical predictions, and increase sensitivity to treatment effects in clinical trials.
| S-EPMC8024352 | biostudies-literature
Project description:Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier (BBB) disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergic receptor agonist that exert protective effects in various central nervous system diseases. The present study was designed to investigate the neuroprotective action of dexmedetomidine in a mouse traumatic brain injury model, and to explore the possible mechanisms. Adult male C57BL/6J mice were subjected to controlled cortical impact. After injury, animals received 3 days of consecutive dexmedetomidine therapy (25 µg/kg per day). The modified neurological severity score was used to assess neurological deficits. The rotarod test was used to evaluate accurate motor coordination and balance. Immunofluorescence was used to determine expression of ionized calcium binding adapter molecule-1, myeloperoxidase, and zonula occluden-1 at the injury site. An enzyme linked immunosorbent assay was used to measure the concentration of interleukin-1β (IL-1β), tumor necrosis factor α, and IL-6. The dry-wet weight method was used to measure brain water content. The Evans blue dye extravasation assay was used to measure BBB disruption. Western blot assay was used to measure protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1 p20, IL-1β, nuclear factor kappa B (NF-κB) p65, occluding, and zonula occluden-1. Flow cytometry was used to measure cellular apoptosis. Results showed that dexmedetomidine treatment attenuated early neurological dysfunction and brain edema. Further, dexmedetomidine attenuated post-traumatic inflammation, up-regulated tight junction protein expression, and reduced secondary BBB damage and apoptosis. These protective effects were accompanied by down-regulation of the NF-κB and NLRP3 inflammasome pathways. These findings suggest that dexmedetomidine exhibits neuroprotective effects against acute (3 days) post-traumatic inflammatory responses, potentially via suppression of NF-κB and NLRP3 inflammasome activation.
| S-EPMC5998618 | biostudies-literature
Project description:Background: We investigated how changes in partial pressure of brain tissue oxygenation (PbtO2) relate to end-tidal carbon dioxide (EtCO2) after pediatric traumatic brain injury (TBI). Methods: Dynamic structural equation modeling (DSEM) was used to investigate associations between EtCO2 and PbtO2, with positive associations indicating intact CO2 reactivity of PbtO2, and negative associations indicating impaired reactivity. Sub-analyses were performed to investigate associations of PbtO2 to intracranial pressure (ICP), arterial blood pressure (ABP) and cerebral regional oximetry (rSO2). Results: Among 14 patients, a positive association between PbtO2 and EtCO2 was demonstrated (SRC 0.05, 95% CI [0.04, 0.06]), with 9 patients demonstrating intact CO2 reactivity and 5 patients demonstrating impaired reactivity. Patients demonstrating intact CO2 reactivity had positive associations between PbtO2 and ICP (0.22 [0.21, 0.23]), whereas patients with impaired reactivity had negative associations (−0.28 [−0.29, −0.28]). Patients demonstrating intact CO2 reactivity had negative associations between PbtO2 and rSO2 (−0.08 [−0.09, −0.08]), whereas patients with impaired reactivity had positive associations (−0.15 [0.14, 0.16]). Compared to patients with intact CO2 reactivity, those with impaired reactivity had increased ICP (p < 0.0000), lower PbtO2 (p < 0.0000) and higher PRx (p = 0.0134). Conclusion: After TBI, CO2 reactivity of PbtO2 can be heterogenous, necessitating further work investigating factors contributing toward impaired reactivity.
| S-EPMC8947728 | biostudies-literature