Traumatic Axonal Injury: Mechanisms and Translational Opportunities

Hill, Ciaran Scott; Coleman, Michael P.; Menon, David

doi:10.1016/j.tins.2016.03.002

Cited by 265 publications

(175 citation statements)

References 140 publications

(179 reference statements)

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“…A typical example is that of a passenger wearing a seatbelt, who sustains brain damage during an automobile rollover without direct impact to the head. Secondary injury is a result of the biochemical cascade following the primary injury in TBI, due to changes in the energy metabolism and protein synthesis/degradation [16].…”

Section: Pathophysiologymentioning

confidence: 99%

“…Another pathway of calcium influx is via "mechanoporation." Mechanoporation is the term used to describe an opening in the axolemma caused by a stretch load on the axon [16]. The increase in intracellular calcium concentration is known to activate calpain, a Ca 2+ -activated protease, leading to proteolysis of structural proteins such as neurofilaments [18].…”

Section: Calcium Influxmentioning

confidence: 99%

“…Activated microglia promote inflammation by releasing cytokines and chemokines. Proinflammatory cytokines are known to cause caspase-mediated proteolysis and microglia recruitment [16]. …”

Section: Phagocytosis and Neuroinflammationmentioning

confidence: 99%

“…This APP is cleaved into amyloid-β peptides, which aggregate into amyloid plaques, the pathological hallmark finding in Alzheimer's disease (AD). Tau, a microtubule-stabilizing protein, has been shown to accumulate perivascularly during the disruption of microtubules [32], suggesting that TBI may be associated with neurodegenerative diseases such as AD [16].…”

Section: Toxic Proteinopathies and Neurodegenerationmentioning

confidence: 99%

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Current State and Prospects of Development of Blood-based Biomarkers for Mild Traumatic Brain Injury

Lee

Seo

et al. 2017

Brain Neurorehabil

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Highlights• There are many unresolved clinical problems about mild traumatic brain injury (mTBI) such as a low sensitivity of standard neuroimaging studies, and absence of reliable predicting models.• It is very difficult to diagnose mTBI in symptomatic patients in the absence of witnesses, clear signs of head trauma, and abnormalities on neuroimaging.• Blood proteins have great potential as diagnostic and prognostic biomarkers of mTBI.• Technological advances in the targeted proteomics are expected to realize the clinical potential of blood-based protein biomarkers. ABSTRACTThe current understanding of the pathophysiology of mild traumatic brain injury (mTBI) is, without doubt, incomplete. Nevertheless, we tried to summarize the state-of-the-art explanation of how the brain is continuously injured even after a single impact. We also reviewed the real struggle of diagnosing mTBI, which culminated in showing the potential of blood-based biomarkers as an alternative or complementary way to overcome this difficulty. Pathophysiology of mTBI is subdivided into primary and secondary injuries. Primary injury is caused by a direct impact on the head and brain. Secondary injury refers to the changes in energy metabolism and protein synthesis/degradation resulting from the biochemical cascades as follows; calcium influx, mitochondrial dysfunction, fractured microtubules, and Wallerian degeneration, neuroinflammation, and toxic proteinopathy. Since the diagnosis of mTBI is made through the initial clinical information, it is difficult and inaccurate to diagnose mTBI without the absence of a witness or sign of head trauma. Blood-based biomarkers are expected to play an important role in diagnosing mTBI and predicting functional outcomes, due to their feasibility and the recent progress of targeted proteomics techniques (i.e., liquid chromatography tandem mass spectrometry [LC-MS/MS]).

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Section: Pathophysiologymentioning

confidence: 99%

Section: Calcium Influxmentioning

confidence: 99%

“…Activated microglia promote inflammation by releasing cytokines and chemokines. Proinflammatory cytokines are known to cause caspase-mediated proteolysis and microglia recruitment [16]. …”

Section: Phagocytosis and Neuroinflammationmentioning

confidence: 99%

Section: Toxic Proteinopathies and Neurodegenerationmentioning

confidence: 99%

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Current State and Prospects of Development of Blood-based Biomarkers for Mild Traumatic Brain Injury

Lee

Seo

et al. 2017

Brain Neurorehabil

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“…TAI is a more severe subtype of TBI than concussion or mild TBI (Table 1) [22]. Neural axons in the white matter appear to be particularly vulnerable to diffuse head injury due to the mechanical loading of the brain during TBI [23,24].…”

Section: Definition Of Cerebral Concussion Mild Tbi and Traumatic Amentioning

confidence: 99%

Diagnostic History of Traumatic Axonal Injury in Patients with Cerebral Concussion and Mild Traumatic Brain Injury

Jang

2016

Brain Neurorehabil

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Highlights• Cerebral concussion and mild traumatic brain injury (TBI) have been used interchangeably, although the two terms have different definitions.• Traumatic axonal injury (TAI) is a more severe subtype of TBI than concussion or mild TBI.• In this review article, we reviewed the history of TAI in patients with concussion and mild TBI. ABSTRACTCerebral concussion and mild traumatic brain injury (TBI) have been used interchangeably, although the two terms have different definitions. Traumatic axonal injury (TAI) is a more severe subtype of TBI than concussion or mild TBI. Regarding the evidence of TAI lesions in patients with concussion or mild TBI, since the 1960's, several studies have reported on TAI in patients with concussion who showed no radiological evidence of brain injury by autopsy. However, conventional CT and MRI are not sensitive to detection of axonal injury in concussion or mild TBI, therefore, previously, diagnosis of TAI in live patients with concussion or mild TBI could not be demonstrated. With the development of diffusion tensor imaging (DTI) in the 1990's, in 2002, Arfanakis et al. reported on TAI lesions in live patients with mild TBI using DTI for the first time. Subsequently, hundreds of studies have demonstrated the usefulness of DTI in detection of TAI and TAI lesions in patients with concussion or mild TBI. In Korea, the term "TAI" has rarely been used in the clinical field while diffuse axonal injury and concussion have been widely used. Rare use of TAI in Korea appeared to be related to slow development of DTI analysis techniques in Korea. Therefore, we think that use of DTI analysis techniques for diagnosis of TAI should be facilitated in Korea.

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Neuroanatomical Substrates and Symptoms Associated With Magnetic Resonance Imaging of Patients With Mild Traumatic Brain Injury

et al. 2021

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Traumatic Axonal Injury: Mechanisms and Translational Opportunities

Cited by 265 publications

References 140 publications

Current State and Prospects of Development of Blood-based Biomarkers for Mild Traumatic Brain Injury

Current State and Prospects of Development of Blood-based Biomarkers for Mild Traumatic Brain Injury

Diagnostic History of Traumatic Axonal Injury in Patients with Cerebral Concussion and Mild Traumatic Brain Injury

Neuroanatomical Substrates and Symptoms Associated With Magnetic Resonance Imaging of Patients With Mild Traumatic Brain Injury

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