Nonspecific white matter degeneration following traumatic brain injury

Gale, Shawn D.; Johnson, Sterling C.; Bigler, Erin D.; Blatter, Duane D.

doi:10.1017/s1355617700000060

Cited by 141 publications

(92 citation statements)

References 16 publications

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“…2), which can be exploited to isolate mechanisms responsible for the recovery observed after human TBI. Clinically, cognitive function can improve after brain injury, despite reductions in brain volume [27].…”

Section: Discussionmentioning

confidence: 99%

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

Lifshitz

Witgen

Grady

2007

Behavioural Brain Research

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Conditioned fear associates a contextual environment and cue stimulus to a foot shock in a single training trial, where fear expressed to the trained context or cue indicates cognitive performance. Lesion, aspiration or inactivation of the hippocampus and amygdala impair conditioned fear to the trained context and cue, respectively. Moreover, only bilateral experimental manipulations, in contrast to unilateral, abolish cognitive performance.In a model of unilateral brain injury, we sought to test whether a single lateral fluid percussion brain injury impairs cognitive performance in conditioned fear. Brain-injured mice were evaluated for anterograde cognitive deficits, with the hypothesis that acute injury-induced impairments improve over time. Male C57BL/6J mice were brain-injured, trained at five or 27 days post-injury, and tested 48 hours later for recall of the association between the conditioned stimuli (trained context or cue) and the unconditioned stimulus (foot shock) by quantifying fear-associated freezing behavior. A significant anterograde hippocampal-dependent cognitive deficit was observed at seven days in brain-injured compared to sham. Cued fear conditioning could not detect amygdala-dependent cognitive deficits after injury and stereological estimation of amygdala neuron number corroborated this finding. The absence of injury-related freezing in a novel context substantiated injury-induced hippocampal-dependent cognitive dysfunction, rather than generalized fear. Variations in the training and testing paradigms demonstrated a cognitive deficit in consolidation, rather than acquisition or recall. By one month post-injury, cognitive function recovered in brain-injured mice. Hence, the acute injury-induced cognitive impairment may persist while transient pathophysiological sequelae are underway, and improve as global dysfunction subsides.

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Section: Discussionmentioning

confidence: 99%

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

Lifshitz

Witgen

Grady

2007

Behavioural Brain Research

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“…Indeed, relatively selective atrophy of the white matter is a common neuroimaging finding years after TBI. 55 As such, there may be a very broad window of therapeutic opportunity to treat DAI spanning the acute and chronic setting. As will be discussed further, however, the exact window of opportunity in relation to specific populations of injured axons remains a matter of controversy.…”

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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“…Blumbergs et al (1995) in a follow-up study demonstrated that the microscopic pathology was on a continuum from mild (GCS of 13-15) to severe (GCS of 3-8), again demonstrating the susceptibility of the fornix. As shown by Viano et al (2005b), the fornix is distinctly vulnerable to the stress0strain effects of concussion and is a common area of damage in moderate-to-severe TBI, as visualized using MRI (Gale et al, 1995;Tate & Bigler, 2000;Tomaiuolo et al, 2004), where the degree of atrophy is related to severity of injury Tate & Bigler, 2000;Tomaiuolo et al, 2004;Wilde et al, 2006b). Because the fornix is a white matter structure containing projecting axons from the hippocampus, disruption in fornix integrity likely relates to the concussive effects of disrupted short-term memory, at least transiently.…”

Section: Is Brain Injury On a Continuum: Concussion R Severe Tbi?mentioning

confidence: 99%

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome

Bigler

2007

J Int Neuropsychol Soc

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363

248

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On the mild end of the acquired brain injury spectrum, the terms concussion and mild traumatic brain injury (mTBI) have been used interchangeably, where persistent post-concussive syndrome (PPCS) has been a label given when symptoms persist for more than three months post-concussion. Whereas a brief history of concussion research is overviewed, the focus of this review is on the current status of PPCS as a clinical entity from the perspective of recent advances in the biomechanical modeling of concussion in human and animal studies, particularly directed at a better understanding of the neuropathology associated with concussion. These studies implicate common regions of injury, including the upper brainstem, base of the frontal lobe, hypothalamic-pituitary axis, medial temporal lobe, fornix, and corpus callosum. Limitations of current neuropsychological techniques for the clinical assessment of memory and executive function are explored and recommendations for improved research designs offered, that may enhance the study of long-term neuropsychological sequelae of concussion. (JINS, 2008, 14, 1-22.)

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Nonspecific white matter degeneration following traumatic brain injury

Cited by 141 publications

References 16 publications

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

Therapy Development for Diffuse Axonal Injury

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome

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