Traumatic brain injuries

Blennow, Kaj; Brody, David L.; Kochanek, Patrick M.; Levin, Harvey S.; McKee, Ann C.; Ribbers, Gerard M.; Yaffe, Kristine; Zetterberg, Henrik

doi:10.1038/nrdp.2016.84

Cited by 460 publications

(390 citation statements)

References 222 publications

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“…For example, similar to joint injuries and the risk of osteoarthritis later in life, traumatic brain injury (TBI) and emotional trauma during early or midlife can increase the risk for late life cognitive impairment and AD and PD (Blennow et al, 2016). In addition, considerable evidence has accumulated demonstrating that the amount, type, and frequency of dietary energy intake, and energy expenditure (exercise), are major determinants of brain health throughout the life course (Mattson et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States

2018

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During aging, the cellular milieu of the brain exhibits tell-tale signs of compromised bioenergetics, impaired adaptive neuroplasticity and resilience, aberrant neuronal network activity, dysregulation of neuronal Ca2+ homeostasis, the accrual of oxidatively modified molecules and organelles, and inflammation. These alterations render the aging brain vulnerable to Alzheimer’s and Parkinson’s diseases and stroke. Emerging findings are revealing mechanisms by which sedentary overindulgent lifestyles accelerate brain aging, whereas lifestyles that include intermittent bioenergetic challenges (exercise, fasting, and intellectual challenges) foster healthy brain aging. Here we provide an overview of the cellular and molecular biology of brain aging, how those processes interface with disease-specific neurodegenerative pathways, and how metabolic states influence brain health.

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Section: Introductionmentioning

confidence: 99%

Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States

2018

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“…Thus, TAT-UCH-L1 has the potential to improve cognitive function when administered weeks or months after TBI. Furthermore, it will be informative to determine the effect of TAT-UCH-L1 treatment upon injury biomarkers such as GFAP and serum UCH-L1[45]. Thus, many additional studies are needed to investigate the administration of TAT-UCH-L1 in the treatment of TBI.…”

Section: Discussionmentioning

confidence: 99%

In vivo transduction of neurons with TAT-UCH-L1 protects brain against controlled cortical impact injury

Líu

Rose

et al. 2017

PLoS ONE

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Many mechanisms or pathways are involved in secondary post-traumatic brain injury, such as the ubiquitin-proteasome pathway (UPP), axonal degeneration and neuronal cell apoptosis. UCH-L1 is a protein that is expressed in high levels in neurons and may have important roles in the UPP, autophagy and axonal integrity. The current study aims to evaluate the role of UCH-L1 in post-traumatic brain injury (TBI) and its potential therapeutic effects. A novel protein was constructed that fused the protein transduction domain (PTD) of trans-activating transduction (TAT) protein with UCH-L1 (TAT-UCH-L1) in order to promote neuronal transduction. The TAT-UCH-L1 protein was readily detected in brain by immunoblotting and immunohistochemistry after i.p. administration in mice. TBI was induced in mice using the controlled cortical impact (CCI) model. TAT-UCH-L1 treatment significantly attenuated K48-linkage polyubiquitin (polyUb)-protein accumulation in hippocampus after CCI compared to vehicle controls, but had no effects on K65-linkage polyUb-protein. TAT-UCH-L1 treatment also attenuated expression of Beclin-1 and LC3BII after CCI. TAT-UCH-L1-treated mice had significantly increased spared tissue volumes and increased survival of CA3 neurons 21 d after CCI compared to control vehicle-treated mice. Axonal injury, detected by APP immunohistochemistry, was reduced in thalamus 24 h and 21 d after CCI in TAT-UCH-L1-treated mice. These results suggest that TAT-UCH-L1 treatment improves function of the UPP and decreases activation of autophagy after CCI. Furthermore, TAT-UCH-L1 treatment also attenuates axonal injury and increases hippocampal neuronal survival after CCI. Taken together these results suggest that UCH-L1 may play an important role in the pathogenesis of cell death and axonal injury after TBI.

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“…Thus, although the focus of the model was to target diffuse swelling, it produced an outcome that might serve to allow exploration of therapies targeting behavioral outcomes. The lack of neuronal death in this model, although felt to represent a limitation back in 2000, when most research focused on severe TBI, might have greater relevance now to pediatric TBI given the importance of mTBI and concussion which have emerged—and where neuronal death is uncommon [52]. …”

Section: Unique Facets Of the Developing Brain—relevance To Pediatricmentioning

confidence: 99%

Pre-clinical models in pediatric traumatic brain injury—challenges and lessons learned

et al. 2017

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PURPOSE Despite the enormity of the problem and the lack of new therapies, research in the pre-clinical arena specifically using pediatric traumatic brain injury (TBI) models is limited. In this review, some of the key models addressing both the age spectrum of pediatric TBI and its unique injury mechanisms will be highlighted. Four topics will be addressed, namely, 1) unique facets of the developing brain important to TBI model development, 2) a description of some of the most commonly used pre-clinical models of severe pediatric TBI including work in both rodents and large animals, 3) a description of the pediatric models of mild TBI and repetitive mild TBI that are relatively new, and finally 4) a discussion of challenges, gaps and potential future directions to further advance work in pediatric TBI models. METHODS This narrative review on the topic of pediatric TBI models was based on review of PUBMED/Medline along with a synthesis of information on key factors in pre-clinical and clinical developmental brain injury that influence TBI modeling. RESULTS In the contemporary literature, six types of models have been used in rats including weight drop, fluid percussion injury (FPI), impact acceleration, controlled cortical impact (CCI), mechanical shaking, and closed head modifications of CCI. In mice, studies are largely restricted to CCI. In large animals, FPI and rotational injury have been used in piglets and shake injury has also been used in lambs. Most of the studies have been in severe injury models, although more recently studies have begun to explore mild and repetitive mild injuries to study concussion. CONCLUSIONS Given the emerging importance of TBI in infants and children, the morbidity and mortality that is produced, along with its purported link to the development of chronic neurodegenerative diseases, studies in these models merit greater systematic investigations along with consortium type approaches and long-term follow-up to translate new therapies to the bedside.

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Traumatic brain injuries

Cited by 460 publications

References 222 publications

Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States

Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States

In vivo transduction of neurons with TAT-UCH-L1 protects brain against controlled cortical impact injury

Pre-clinical models in pediatric traumatic brain injury—challenges and lessons learned

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