Histologic Changes in the Brain in Cases of Fatal Injury to the Head

Rand, Carl W.; Courville, Cyril B.

doi:10.1001/archneurpsyc.1932.02230150121007

Cited by 36 publications

(11 citation statements)

References 11 publications

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“…Commonly, swellings appear in a periodic arrangement along the length of an axon at the site of injury, classically referred to as “axonal varicosities,” or as a large single swelling at a disconnected axon terminal described as an “axonal bulb” (previously referred to as a “retraction ball”) (Cajal, 1928; Rand and Courville, 1946; Strich, 1956; Adams et al, 1982, 1984; Povlishock et al, 1983, 1999; Povlishock and Becker, 1985; Adams et al, 1989; Povlishock, 1992; Chen et al, 1999; Smith and Meaney, 2000; Smith et al, 2003; Povlishock and Katz, 2005). The histopathologic gold standard for the identification of DAI is achieved via immunohistochemistry to visualize damaged axons accumulating the amyloid precursor protein (APP) (Gentleman et al, 1993; Sherriff et al, 1994).…”

Section: Models Of Traumatic Axonal Injurymentioning

confidence: 99%

Animal models of traumatic brain injury

Johnson

Meaney

Cullen

et al. 2015

Handbook of Clinical Neurology

131

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Section: Models Of Traumatic Axonal Injurymentioning

confidence: 99%

Animal models of traumatic brain injury

Johnson

Meaney

Cullen

et al. 2015

Handbook of Clinical Neurology

131

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“…3,6,11 More modern approaches using antibodies to transported proteins, Research, NICHD, NIH such as amyloid precursor protein (APP), however, have become the gold standard in evaluating the occurrence of DAI in both the routine neuropathologic and forensic settings as well as animal investigations. 10,[12][13][14][15][16][17][18] Specifically, as APP moves down the axonal cylinder via anterograde axonal transport, any focal disruption/ perturbation of the axon and its transport kinetics can lead to local swelling that then can be easily identified by the pooling of APP.…”

Section: Histopathological Identification Of Daimentioning

confidence: 99%

“…31 This common pathological profile found in acute TBI may reflect a process whereby transport is only partially interrupted at multiple sites along the axon's length, producing the string-of-beads appearance, in contrast with presumed complete interruption at one site forming singular axonal bulbs. 3,11,24,31 Typically in humans, reactive axonal swellings can be recognized within the first hours post-injury as large focal axonal swellings 10-20 lm in diameter that expand in size over 24-48 h reaching up to approximately 50 lm. 1,3,8,15,18,25,32 During this time, both axonal bulbs and varicosities are often observed together in various ratios, presumably reflecting the different rates of swelling and progression toward disconnection in individual injured axons.…”

Section: Histopathological Identification Of Daimentioning

confidence: 99%

Therapy Development for Diffuse Axonal Injury

Smith

Hicks

Povlishock

2013

Journal of Neurotrauma

174

146

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Diffuse axonal injury (DAI) remains a prominent feature of human traumatic brain injury (TBI) and a major player in its subsequent morbidity. The importance of this widespread axonal damage has been confirmed by multiple approaches including routine postmortem neuropathology as well as advanced imaging, which is now capable of detecting the signatures of traumatically induced axonal injury across a spectrum of traumatically brain-injured persons. Despite the increased interest in DAI and its overall implications for brain-injured patients, many questions remain about this component of TBI and its potential therapeutic targeting. To address these deficiencies and to identify future directions needed to fill critical gaps in our understanding of this component of TBI, the National Institute of Neurological Disorders and Stroke hosted a workshop in May 2011. This workshop sought to determine what is known regarding the pathogenesis of DAI in animal models of injury as well as in the human clinical setting. The workshop also addressed new tools to aid in the identification of this axonal injury while also identifying more rational therapeutic targets linked to DAI for continued preclinical investigation and, ultimately, clinical translation. This report encapsulates the oral and written components of this workshop addressing key features regarding the pathobiology of DAI, the biomechanics implicated in its initiating pathology, and those experimental animal modeling considerations that bear relevance to the biomechanical features of human TBI. Parallel considerations of alternate forms of DAI detection including, but not limited to, advanced neuroimaging, electrophysiological, biomarker, and neurobehavioral evaluations are included, together with recommendations for how these technologies can be better used and integrated for a more comprehensive appreciation of the pathobiology of DAI and its overall structural and functional implications. Lastly, the document closes with a thorough review of the targets linked to the pathogenesis of DAI, while also presenting a detailed report of those target-based therapies that have been used, to date, with a consideration of their overall implications for future preclinical discovery and subsequent translation to the clinic. Although all participants realize that various research gaps remained in our understanding and treatment of this complex component of TBI, this workshop refines these issues providing, for the first time, a comprehensive appreciation of what has been done and what critical needs remain unfulfilled.

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“…However, in Korea, it has rarely been used in the clinical field while diffuse axonal injury (DAI) and concussion have been widely used. Since the middle of the last century, several studies have demonstrated trauma related axonal injury in the human brain using autopsy [35]. In 1982, Adams et al [36], who introduced the term "DAI" by characterizing the extent and distribution of axonal injury in patients with TBI, defined DAI as the presence of microscopic axonal injury in the white matter of the cerebral hemisphere, corpus callosum, and brainstem caused by mechanical forces following head trauma [37,38].…”

Section: History Of Traumatic Axonal Injury In Concussion and Mild Tbimentioning

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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Histologic Changes in the Brain in Cases of Fatal Injury to the Head

Cited by 36 publications

References 11 publications

Animal models of traumatic brain injury

Animal models of traumatic brain injury

Therapy Development for Diffuse Axonal Injury

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

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