Traumatic Brain Injury as a Trigger of Neurodegeneration

Johnson, Victoria E.; Stewart, William; Arena, John D.; Smith, Douglas H.

doi:10.1007/978-3-319-57193-5_15

Cited by 84 publications

(54 citation statements)

References 138 publications

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“…In the present study, we have revealed that widespread degenerating neurons are increased in the cortex, striatum, and hippocampal CA1 in both hemispheres long-term 24 weeks after a severe CCI-TBI. It has been shown that the widespread neurodegeneration after TBI is tightly linked to cognitive impairments [13,40]. The present study has demonstrated that SCF+G-CSF ameliorates long-term neurodegeneration in the contralateral frontal cortex and hippocampus remote from the injury site.…”

Section: Discussionsupporting

confidence: 66%

The Contribution of Stem Cell Factor and Granulocyte-Colony Stimulating Factor in Reducing Neurodegeneration and Promoting Neural Network Reorganization after Traumatic Brain Injury

Russell

Qiu

et al. 2019

Preprint

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Background Traumatic brain injury (TBI) is a major cause of death and disability in young adults worldwide. TBI-induced long-term cognitive deficits represent a growing clinical problem.Stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF)play a role in neuroprotection and neuronal plasticity.However, the knowledge concerning reparative efficacy of SCF+G-CSF treatment in post-acute TBI recovery remains incomplete. This study aims to determine the effectsof stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) on post-TBI recovery in young adult mice. The controlled cortical impact model of TBI was used for inducing a severe damage in the motor cortex of the right hemisphere in 8-week-old male C57BL mice. The combination treatment of SCF and G-CSF (SCF+G-CSF) was initiated 3 weeks after induction of TBI. Results Severe TBI led to persistent motor functional deficits (Rota-Rod test) and impaired spatial learning and memory (Morris water maze test). SCF+G-CSF treatment significantly improved the severe TBI-impaired spatial learning and memory at 6 weeks post-treatment.TBI also caused significant increases of Fluoro-Jade C positive degenerating neurons in bilateral frontal cortex, striatum and hippocampus, and significant reductions in MAP2+apical dendrites and overgrowth of SMI312+axons in peri-TBI cavity frontal cortex and in the ipsilateral hippocampal CA1 at 24 weeks post-TBI. SCF+G-CSF treatment significantly reduced TBI-induced neurodegeneration in the contralateral frontal cortex and hippocampal CA1, increased MAP2+apical dendrites in the peri-TBI cavity frontal cortex, and prevented TBI-induced axonal overgrowth in both the peri-TBI cavity frontal cortex and ipsilateral hippocampal CA1. Conclusions These findings reveal a novel pathology of axonal overgrowth after TBI and demonstrate a therapeutic potential of SCF+G-CSF in ameliorating TBI-induced long-term neuronal pathology, neural network malformation, and impairments in spatial learning and memory.

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Section: Discussionsupporting

confidence: 66%

The Contribution of Stem Cell Factor and Granulocyte-Colony Stimulating Factor in Reducing Neurodegeneration and Promoting Neural Network Reorganization after Traumatic Brain Injury

Russell

Qiu

et al. 2019

Preprint

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“…155 (c) Rat-Aβ(1-16) dimer (Zn 2+ ); pdb 2li9. The rat Aβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) peptide also binds Zn 2+ and other metal ions, despite lacking the His13 residue of human Aβ chemical shifts), while in mature fibrils, these residues extend the N-terminal β-strand segment.…”

Section: Metal Ionsmentioning

confidence: 99%

β‐Amyloid aggregation and heterogeneous nucleation

et al. 2019

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In this article, we consider the role of heterogeneous nucleation in β‐amyloid aggregation. Heterogeneous nucleation is more common and occurs at lower levels of supersaturation than homogeneous nucleation. The nucleation period is also the stage at which most of the polymorphism of amyloids arises, this being one of the defining features of amyloids. We focus on several well‐known heterogeneous nucleators of β‐amyloid, including lipid surfaces, especially those enriched in gangliosides and cholesterol, and divalent metal ions. These two broad classes of nucleators affect β‐amyloid particularly in light of the amphiphilicity of these peptides: the N‐terminal region, which is largely polar and charged, contains the metal binding site, whereas the C‐terminal region is aliphatic and is important in lipid binding. Notably, these two classes of nucleators can interact cooperatively, aggregation begetting greater aggregation.

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“…DAI, as a type of TBI, is associated with cytoskeletal alterations, represented by swellings or varicosities along the axons and terminal bulbs [ 34 , 35 , 36 ]. These axonal alterations may be caused by mechanical disruption, and subsequent increasing intracellular Ca 2+ influx by the breaches in the axolemma [ 37 , 38 , 39 ].…”

Section: Tbi and Oxidative Stressmentioning

confidence: 99%

Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review

Frati

Cerretani

Fiaschi

et al. 2017

IJMS

129

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Traumatic brain injury (TBI) is one of the world’s leading causes of morbidity and mortality among young individuals. TBI applies powerful rotational and translational forces to the brain parenchyma, which results in a traumatic diffuse axonal injury (DAI) responsible for brain swelling and neuronal death. Following TBI, axonal degeneration has been identified as a progressive process that starts with disrupted axonal transport causing axonal swelling, followed by secondary axonal disconnection and Wallerian degeneration. These modifications in the axonal cytoskeleton interrupt the axoplasmic transport mechanisms, causing the gradual gathering of transport products so as to generate axonal swellings and modifications in neuronal homeostasis. Oxidative stress with consequent impairment of endogenous antioxidant defense mechanisms plays a significant role in the secondary events leading to neuronal death. Studies support the role of an altered axonal calcium homeostasis as a mechanism in the secondary damage of axon, and suggest that calcium channel blocker can alleviate the secondary damage, as well as other mechanisms implied in the secondary injury, and could be targeted as a candidate for therapeutic approaches. Reactive oxygen species (ROS)-mediated axonal degeneration is mainly caused by extracellular Ca2+. Increases in the defense mechanisms through the use of exogenous antioxidants may be neuroprotective, particularly if they are given within the neuroprotective time window. A promising potential therapeutic target for DAI is to directly address mitochondria-related injury or to modulate energetic axonal energy failure.

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Traumatic Brain Injury as a Trigger of Neurodegeneration

Cited by 84 publications

References 138 publications

The Contribution of Stem Cell Factor and Granulocyte-Colony Stimulating Factor in Reducing Neurodegeneration and Promoting Neural Network Reorganization after Traumatic Brain Injury

The Contribution of Stem Cell Factor and Granulocyte-Colony Stimulating Factor in Reducing Neurodegeneration and Promoting Neural Network Reorganization after Traumatic Brain Injury

β‐Amyloid aggregation and heterogeneous nucleation

Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review

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