Early detection of axonal injury after human head trauma using immunocytochemistry for ?-amyloid precursor protein

Sherriff, F. E.; Bridges, Leslie; Sivaloganathan, S.

doi:10.1007/bf00386254

Cited by 319 publications

(176 citation statements)

References 19 publications

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“…Alternatively, it may be that our measures were not sensitive enough. Finally, the mild TBI group may have sustained reversible axonal injury (Gentleman et al, 1995;Sherriff et al, 1994) or transient biochemical changes. This raises the additional possibility that the deficits found in the mild TBI group may partially or completely resolve over time.…”

Section: Discussionmentioning

confidence: 99%

Neuropsychological and information processing deficits following mild traumatic brain injury

Mathias

Beall

Bigler

2004

J Int Neuropsychol Soc

120

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Neuroradiological and neuropathological investigations have found evidence of diffuse brain damage in the frontal and temporal lobes, corpus callosum, and fornices in patients who have sustained a mild traumatic brain injury (TBI). However, neuropsychological assessments of these patients do not typically target many of the subtle information processing deficits that may arise from diffuse damage involving the frontotemporal regions of the brain as well as white matter pathology, including the corpus callosum. Consequently, we have a limited understanding of the deficits that may be attributable to temporary or permanent disruptions to these functional pathways. This study assessed a group of mild TBI patients (N 5 40) and a matched control group (N 5 40) on a number of standard neuropsychological tests of selective and sustained attention, verbal and non-verbal fluency, and verbal memory. In addition, reaction time (RT) tasks, requiring both the inter-and intra-hemispheric processing of visual and tactile information, were used to assess the functional integrity of the tracts that are likely to be affected by diffuse damage. In the 1st month after sustaining their injury, the mild TBI group demonstrated deficits in attention, non-verbal fluency, and verbal memory. They also demonstrated slower visual and tactile RTs, with the visual RTs of mild TBI patients being more affected by increased task difficulty and the need to transfer information across the corpus callosum, than did their matched controls. (JINS, 2004, 10, 286-297.)

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Section: Discussionmentioning

confidence: 99%

Neuropsychological and information processing deficits following mild traumatic brain injury

Mathias

Beall

Bigler

2004

J Int Neuropsychol Soc

120

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“…Primary axotomy can occur with severe insults, leading to disconnection of axon processes and to axonal swelling. Secondary axotomy can result in an inhibition of axoplasmic flow as evidenced by ß-APP accumulation after human (Gentleman et al, 1993;Sheriff et al, 1994) and experimental TBI (Bramlett et al, 1997b;Pierce et al, 1996) (Fig. 1B).…”

Section: White Matter Vulnerabilitymentioning

confidence: 98%

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

Bramlett

Dietrich

2004

J Cereb Blood Flow Metab

562

358

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Summary: Current knowledge regarding the pathophysiology of cerebral ischemia and brain trauma indicates that similar mechanisms contribute to loss of cellular integrity and tissue destruction. Mechanisms of cell damage include excitotoxicity, oxidative stress, free radical production, apoptosis and inflammation. Genetic and gender factors have also been shown to be important mediators of pathomechanisms present in both injury settings. However, the fact that these injuries arise from different types of primary insults leads to diverse cellular vulnerability patterns as well as a spectrum of injury processes. Blunt head trauma produces shear forces that result in primary membrane damage to neuronal cell bodies, white matter structures and vascular beds as well as secondary injury mechanisms. Severe cerebral ischemic insults lead to metabolic stress, ionic perturbations, and a complex cascade of biochemical and molecular events ultimately causing neuronal death. Similarities in the pathogenesis of these cerebral injuries may indicate that therapeutic strategies protective following ischemia may also be beneficial after trauma. This review summarizes and contrasts injury mechanisms after ischemia and trauma and discusses neuroprotective strategies that target both types of injuries.

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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. 19,20 Through the use of these antibodies in both neuropathologic and forensic settings, the overall occurrence and distribution of traumatically induced axonal change has become even more apparent and has extended many of those observations initially made via the use of more traditional histological approaches (Fig.…”

Section: Histopathological Identification Of Daimentioning

confidence: 99%

Therapy Development for Diffuse Axonal Injury

Smith

Hicks

Povlishock

2013

Journal of Neurotrauma

171

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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Early detection of axonal injury after human head trauma using immunocytochemistry for ?-amyloid precursor protein

Cited by 319 publications

References 19 publications

Neuropsychological and information processing deficits following mild traumatic brain injury

Neuropsychological and information processing deficits following mild traumatic brain injury

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

Therapy Development for Diffuse Axonal Injury

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