scholarly journals Rapid disruption of the cortical microcirculation after mild traumatic brain injury

2019 ◽  
Author(s):  
Ellen D. Witkowski ◽  
Şefik Evren Erdener ◽  
Kıvılcım Kılıç ◽  
Sreekanth Kura ◽  
Jianbo Tang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Vascular Dysfunction ◽  
Metabolic Stress ◽  
Time Lapse ◽  
Post Injury ◽  
Injury Model ◽  
Time Lapse Imaging

AbstractTraumatic brain injury (TBI) is a major source of cognitive deficits affecting millions annually. The bulk of human injuries are mild, causing little or no macroscopic damage to neural tissue, yet can still lead to long-term neuropathology manifesting months or years later. Although the cellular stressors that ultimately lead to chronic pathology are poorly defined, one notable candidate is metabolic stress due to reduced cerebral blood flow (CBF), which is common to many forms of TBI. Here we used high-resolution in vivo intracranial imaging in a rodent injury model to characterize deficits in the cortical microcirculation during both acute and chronic phases after mild TBI. We found that CBF dropped precipitously during immediate post-injury periods, decreasing to less than half of baseline levels within minutes and remaining suppressed for 1.5-2 hours. Repeated time-lapse imaging of the cortical microvasculature revealed further striking flow deficits in the capillary network, where 18% of vessels were completely occluded for extended periods after injury, and an additional >50% showed substantial stoppages. Decreased CBF was paralleled by extensive vasoconstriction that is likely to contribute to loss of flow. Our data indicate a major role for vascular dysfunction in even mild forms of TBI, and suggest that acute post-injury periods may be key therapeutic windows for interventions that restore flow and mitigate metabolic stress.

scholarly journals 513 Understanding the Role of HMGB1 Post-Traumatic Brain Injury - The Complex Interplay Between Neuro-Inflammation and Neurogenesis

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
O Marei ◽  
S Manivannan ◽  
O Elalfy ◽  
M Zaben
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Current Evidence ◽  
Post Injury ◽  
Term Survival ◽  
Positive Effects ◽  
Pubmed Database ◽  
Post Traumatic

Abstract Introduction Traumatic brain injury (TBI) is a global public health burden. Although neurogenesis occurs post-injury, achieving long term survival of newly generated neurons remains elusive. High Mobility Group Box protein 1 (HMGB1) is a pivotal cytokine in hosting the neuro-inflammatory response to injury, but also mediates neurogenesis during physiological development. In this review, we examine current evidence for post-traumatic neurogenesis and HMGB1 as a therapeutic target. Method PubMed database was evaluated with the following search terms: HMGB1, isoforms, neurogenesis, traumatic brain injury, Toll-like receptor, receptor for advanced glycation end-products. Results Multiple studies support the existence of neurogenesis post-injury both in vitro and in vivo. Different HMGB1 target receptors mediate different functions of HMGB1, though these are not mutually exclusive in the context of injury. Interaction with RAGE is responsible for developmental neurogenesis, whilst TLR-4 mediates the innate immune response. Though different HMGB1 isoforms are recognised, specific effects post-injury remains unexplored. In vivo animal studies demonstrate positive effects of HMGB1 antagonism post-TBI, but long-term outcomes remain unclear. Conclusions Modulating HMGB1 may enhance post-TBI recovery, but a mechanistic understanding of its effects on neurogenesis is fundamental to avoid negating potentially beneficial effects.

scholarly journals Long-Term Survival Following Traumatic Brain Injury: A Population-Based Parametric Survival Analysis

2016 ◽  
Vol 47 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Gordon W. Fuller ◽  
Jeanine Ransom ◽  
Jay Mandrekar ◽  
Allen W. Brown
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
General Population ◽  
Life Expectancy ◽  
Health Planning ◽  
Population Based ◽  
Post Injury ◽  
Term Survival ◽  
Parametric Survival

Background: Long-term mortality may be increased following traumatic brain injury (TBI); however, the degree to which survival could be reduced is unknown. We aimed at modelling life expectancy following post-acute TBI to provide predictions of longevity and quantify differences in survivorship with the general population. Methods: A population-based retrospective cohort study using data from the Rochester Epidemiology Project (REP) was performed. A random sample of patients from Olmsted County, Minnesota with a confirmed TBI between 1987 and 2000 was identified and vital status determined in 2013. Parametric survival modelling was then used to develop a model to predict life expectancy following TBI conditional on age at injury. Survivorship following TBI was also compared with the general population and age- and gender-matched non-head injured REP controls. Results: Seven hundred and sixty nine patients were included in complete case analyses. The median follow-up time was 16.1 years (interquartile range 9.0-20.4) with 120 deaths occurring in the cohort during the study period. Survival after acute TBI was well represented by a Gompertz distribution. Victims of TBI surviving for at least 6 months post-injury demonstrated a much higher ongoing mortality rate compared to the US general population and non-TBI controls (hazard ratio 1.47, 95% CI 1.15-1.87). US general population cohort life table data was used to update the Gompertz model's shape and scale parameters to account for cohort effects and allow prediction of life expectancy in contemporary TBI. Conclusions: Survivors of TBI have decreased life expectancy compared to the general population. This may be secondary to the head injury itself or result from patient characteristics associated with both the propensity for TBI and increased early mortality. Post-TBI life expectancy estimates may be useful to guide prognosis, in public health planning, for actuarial applications and in the extrapolation of outcomes for TBI economic models.

scholarly journals Exosomal MicroRNA Differential Expression in Plasma of Young Adults with Chronic Mild Traumatic Brain Injury and Healthy Control

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 36
Author(s):  
Rany Vorn ◽  
Maiko Suarez ◽  
Jacob C. White ◽  
Carina A. Martin ◽  
Hyung-Suk Kim ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Young Adults ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Pathophysiological Mechanism ◽  
Post Injury ◽  
Persistent Symptoms ◽  
Healthy Control ◽  
Underlying Mechanisms

Chronic mild traumatic brain injury (mTBI) has long-term consequences, such as neurological disability, but its pathophysiological mechanism is unknown. Exosomal microRNAs (exomiRNAs) may be important mediators of molecular and cellular changes involved in persistent symptoms after mTBI. We profiled exosomal microRNAs (exomiRNAs) in plasma from young adults with or without a chronic mTBI to decipher the underlying mechanisms of its long-lasting symptoms after mTBI. We identified 25 significantly dysregulated exomiRNAs in the chronic mTBI group (n = 29, with 4.48 mean years since the last injury) compared to controls (n = 11). These miRNAs are associated with pathways of neurological disease, organismal injury and abnormalities, and psychological disease. Dysregulation of these plasma exomiRNAs in chronic mTBI may indicate that neuronal inflammation can last long after the injury and result in enduring and persistent post-injury symptoms. These findings are useful for diagnosing and treating chronic mTBIs.

scholarly journals Traumatic Brain Injury as a Disorder of Brain Connectivity

2016 ◽  
Vol 22 (2) ◽  
pp. 120-137 ◽  
Author(s):  
Jasmeet P. Hayes ◽  
Erin D. Bigler ◽  
Mieke Verfaellie
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Functional Connectivity ◽  
Negative Impact ◽  
Axonal Injury ◽  
Resting State Functional Connectivity ◽  
Post Injury ◽  
Recent Advances

AbstractObjectives:Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition.Methods:We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury.Results:The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes.Conclusions:TBI has a negative impact on distributed brain networks that lead to behavioral disturbance. (JINS, 2016,22, 120–137)

scholarly journals Outcomes after Complicated and Uncomplicated Mild Traumatic Brain Injury at Three-and Six-Months Post-Injury: Results from the CENTER-TBI Study

2020 ◽  
Vol 9 (5) ◽  
pp. 1525 ◽  
Author(s):  
Daphne C. Voormolen ◽  
Marina Zeldovich ◽  
Juanita A. Haagsma ◽  
Suzanne Polinder ◽  
Sarah Friedrich ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Functional Outcome ◽  
Mild Traumatic Brain Injury ◽  
Intracranial Injury ◽  
Post Injury ◽  
Long Term Outcome ◽  
Sf 36 ◽  
Disease Specific

The objective of this study was to provide a comprehensive examination of the relation of complicated and uncomplicated mild traumatic brain injury (mTBI) with multidimensional outcomes at three- and six-months after TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) research project. Patients after mTBI (Glasgow Coma scale (GCS) score of 13–15) enrolled in the study were differentiated into two groups based on computed tomography (CT) findings: complicated mTBI (presence of any traumatic intracranial injury on first CT) and uncomplicated mTBI (absence of any traumatic intracranial injury on first CT). Multidimensional outcomes were assessed using seven instruments measuring generic and disease-specific health-related quality of life (HRQoL) (SF-36 and QOLIBRI), functional outcome (GOSE), and psycho-social domains including symptoms of post-traumatic stress disorder (PTSD) (PCL-5), depression (PHQ-9), and anxiety (GAD-7). Data were analyzed using a multivariate repeated measures approach (MANOVA-RM), which inspected mTBI groups at three- and six-months post injury. Patients after complicated mTBI had significantly lower GOSE scores, reported lower physical and mental component summary scores based on the SF-36 version 2, and showed significantly lower HRQoL measured by QOLIBRI compared to those after uncomplicated mTBI. There was no difference between mTBI groups when looking at psychological outcomes, however, a slight improvement in PTSD symptoms and depression was observed for the entire sample from three to six months. Patients after complicated mTBI reported lower generic and disease specific HRQoL and worse functional outcome compared to individuals after uncomplicated mTBI at three and six months. Both groups showed a tendency to improve from three to six months after TBI. The complicated mTBI group included more patients with an impaired long-term outcome than the uncomplicated group. Nevertheless, patients, clinicians, researchers, and decisions-makers in health care should take account of the short and long-term impact on outcome for patients after both uncomplicated and complicated mTBI.

TP2-3 Long-term survival and five year hospital resource usage following traumatic brain injury in scotland from 1997–2015: a population-based retrospective cohort study

2019 ◽  
Vol 90 (3) ◽  
pp. e14.2-e14
Author(s):  
JJM Loan ◽  
NW Scott ◽  
JO Jansen
Keyword(s):  
Traumatic Brain Injury ◽  
Cohort Study ◽  
Brain Injury ◽  
Population Based ◽  
Resource Usage ◽  
Hospital Resource ◽  
Post Injury ◽  
Term Survival ◽  
Long Term Survival

AimTo determine if survival and hospital resource usage differ following traumatic brain injury (TBI) compared with head injury without neurological injury(HI).MethodsThis retrospective population-based cohort study included all 25 319 patients admitted to a Scottish NHS hospital from 1997–2015 with TBI. Participants were identified using previously validated ICD-10 based definitions. For comparison, all 194 049 HI cases were identified. Our main outcome measures were hazards of all-cause mortality after TBI, compared with HI, over 18 years follow-up period; and odds of mortality at one month post-injury. Number of days spent as inpatients and number of outpatient attendances per surviving month post-injury were used as measures of resource utilisation.ResultsThe adjusted odds ratio for mortality in the first month post-injury for TBI was 7.12 (95% confidence interval [CI] 6.73–7.52; p<0.001). For the remaining 18 year study period, the hazards of morality after TBI were 0.93 (CI 0.90–0.96; p<0.001). TBI was associated with 2.15 (CI 2.10–2.20; p<0.001) more days spent as inpatient and 1.09 times more outpatient attendances (CI 1.07–1.11; p<0.001) than HI.ConclusionsAlthough initial mortality following TBI is high, survivors of the first month can achieve comparable long-term survival to HI. However this is associated with increased utilisation of hospital services in the TBI group.

Addressing the Sexual Concerns of Persons With Traumatic Brain Injury in Rehabilitation Settings: A Framework for Action

2001 ◽  
Vol 2 (2) ◽  
pp. 97-108 ◽  
Author(s):  
Grahame Simpson
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
World Health Organisation ◽  
World Health ◽  
Post Injury ◽  
Rehabilitation Programs ◽  
Human Functioning ◽  
Sexual Concerns ◽  
Organisational Structures

AbstractTraumatic brain injury (TBI) impacts upon people's sexuality with 50% to 60% of persons reporting some level of disruption post-injury. However, only small proportions of patients/family members report that rehabilitation health professionals made inquiries about whether they had any sexual concerns. Rehabilitation programs have a responsibility to meet the challenge of addressing this important area of human functioning. An agency framework is described that provides a non-threatening, structured way for services to conceptualise, introduce or upgrade sexuality services in a manner that can be maintained over the long term. The framework contains an underlying philosophy of sexuality, five proposed modalities of service provision and detail of the underlying organisational structures that are required to provide sexuality services with consistency and effectiveness over the long term. Finally, organisational strategies that can be employed to implement the framework are discussed as well as suggestions about the sequencing of such strategies. By using the framework, rehabilitation services can put sexuality back onto their treatment agenda, as they seek to restore patients/clients with TBI to the “highest level of adaptation attainable” (World Health Organisation, 1996, p. 1) in all areas of their lives.

scholarly journals Long-term in vivo time-lapse imaging of synapse development and plasticity in the cerebellum

2014 ◽  
Vol 111 (1) ◽  
pp. 208-216 ◽  
Author(s):  
Naoko Nishiyama ◽  
Jeremy Colonna ◽  
Elise Shen ◽  
Jennifer Carrillo ◽  
Hiroshi Nishiyama
Keyword(s):  
In Vivo Imaging ◽  
Time Window ◽  
Time Lapse ◽  
Mammalian Brain ◽  
Cerebellar Neurons ◽  
Brain Functions ◽  
Time Lapse Imaging ◽  
Synaptic Circuitry

Synapses are continuously formed and eliminated throughout life in the mammalian brain, and emerging evidence suggests that this structural plasticity underlies experience-dependent changes of brain functions such as learning and long-term memory formation. However, it is generally difficult to understand how the rewiring of synaptic circuitry observed in vivo eventually relates to changes in animal's behavior. This is because afferent/efferent connections and local synaptic circuitries are very complicated in most brain regions, hence it is largely unclear how sensorimotor information is conveyed, integrated, and processed through a brain region that is imaged. The cerebellar cortex provides a particularly useful model to challenge this problem because of its simple and well-defined synaptic circuitry. However, owing to the technical difficulty of chronic in vivo imaging in the cerebellum, it remains unclear how cerebellar neurons dynamically change their structures over a long period of time. Here, we showed that the commonly used method for neocortical in vivo imaging was not ideal for long-term imaging of cerebellar neurons, but simple optimization of the procedure significantly improved the success rate and the maximum time window of chronic imaging. The optimized method can be used in both neonatal and adult mice and allows time-lapse imaging of cerebellar neurons for more than 5 mo in ∼80% of animals. This method allows vital observation of dynamic cellular processes such as developmental refinement of synaptic circuitry as well as long-term changes of neuronal structures in adult cerebellum under longitudinal behavioral manipulations.

scholarly journals A Role for Nanoparticles in Treating Traumatic Brain Injury

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 473 ◽  
Author(s):  
Badrul Alam Bony ◽  
Forrest M. Kievit
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Treatment Options ◽  
Unmet Need ◽  
Economic Loss ◽  
Phase Iii ◽  
Target Engagement ◽  
Post Injury ◽  
The Brain

Traumatic brain injury (TBI) is one of the main causes of disability in children and young adults, as well as a significant concern for elderly individuals. Depending on the severity, TBI can have a long-term impact on the quality of life for survivors of all ages. The primary brain injury can result in severe disability or fatality, and secondary brain damage can increase the complexities in cellular, inflammatory, neurochemical, and metabolic changes in the brain, which can last decades post-injury. Thus, survival from a TBI is often accompanied by lifelong disabilities. Despite the significant morbidity, mortality, and economic loss, there are still no effective treatment options demonstrating an improved outcome in a large multi-center Phase III trial, which can be partially attributed to poor target engagement of delivered therapeutics. Thus, there is a significant unmet need to develop more effective delivery strategies to overcome the biological barriers that would otherwise inhibit transport of materials into the brain to prevent the secondary long-term damage associated with TBI. The complex pathology of TBI involving the blood-brain barrier (BBB) has limited the development of effective therapeutics and diagnostics. Therefore, it is of great importance to develop novel strategies to target the BBB. The leaky BBB caused by a TBI may provide opportunities for therapeutic delivery via nanoparticles (NP). The focus of this review is to provide a survey of NP-based strategies employed in preclinical models of TBI and to provide insights for improved NP based diagnostic or treatment approaches. Both passive and active delivery of various NPs for TBI are discussed. Finally, potential therapeutic targets where improved NP-mediated delivery could increase target engagement are identified with the overall goal of providing insight into open opportunities for NP researchers to begin research in TBI.

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