Traumatic brain injuries: structural changes

Cervós-Navarro, J.; Lafuente, José Vicente

doi:10.1016/0022-510x(91)90002-o

Cited by 90 publications

(43 citation statements)

References 42 publications

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“…The controlled cortical impact model produces a central contusion and surrounding pericontusional axonal injury, whereas much of the traumatic axonal injury in humans occurs in a scattered, multifocal distribution. The axonal injury in our mouse model may be most directly analogous to the well-described subset of pericontusional white matter lesions seen in human TBI patients (Cervos-Navarro and Lafuente, 1991;Strich, 1961). While the mechanisms of injury differ (direct cortical impact in the mice vs. deformation of the brain within the skull in humans), the characteristics of the pericontusional white matter injury in mice and humans are quite similar overall (CervosNavarro and Lafuente, 1991;Strich, 1961).…”

Section: Discussionmentioning

confidence: 63%

“…The axonal injury in our mouse model may be most directly analogous to the well-described subset of pericontusional white matter lesions seen in human TBI patients (Cervos-Navarro and Lafuente, 1991;Strich, 1961). While the mechanisms of injury differ (direct cortical impact in the mice vs. deformation of the brain within the skull in humans), the characteristics of the pericontusional white matter injury in mice and humans are quite similar overall (CervosNavarro and Lafuente, 1991;Strich, 1961). In addition, the histological features of these pericontusional injuries are comparable to those seen in white matter that is not immediately adjacent to contusions (Cervos-Navarro and Lafuente, 1991), and the signal abnormalities detected using DTI in our study are concordant with those seen in such injuries (Arfanakis et al, 2002;Huisman et al, 2004;Inglese et al, 2005).…”

Section: Discussionmentioning

confidence: 77%

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Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Donald

Dikranian

Song

et al. 2007

Experimental Neurology

273

209

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Traumatic axonal injury (TAI) is thought to be a major contributor to cognitive dysfunction following traumatic brain injury (TBI), however TAI is difficult to diagnose or characterize non-invasively. Diffusion tensor imaging (DTI) has shown promise in detecting TAI, but direct comparison to histologically-confirmed axonal injury has not been performed. In the current study, mice were imaged with DTI, subjected to a moderate cortical controlled impact injury, and re-imaged 4-6 hours and 24 hours post-injury. Axonal injury was detected by amyloid beta precursor protein (APP) and neurofilament immunohistochemistry in pericontusional white matter tracts. The severity of axonal injury was quantified using stereological methods from APP stained histological sections. Two DTI parameters -axial diffusivity and relative anisotropy -were significantly reduced in the injured, pericontusional corpus callosum and external capsule, while no significant changes were seen with conventional MRI in these regions. The contusion was easily detectible on all MRI sequences. Significant correlations were found between changes in relative anisotropy and the density of APP tained axons across mice and across subregions spanning the spatial gradient of injury. The predictive value of DTI was tested using a region with DTI changes (hippocampal commissure) and a region without DTI changes (anterior commissure). Consistent with DTI predictions, there was histological detection of axonal injury in the hippocampal commissure and none in the anterior commissure.Corresponding Author: David Brody, MD PhD, Department of Neurology, Washington University, 660 S. Euclid, Campus Box 8111, St. Louis, MO 63110, Phone: 314-747-0286, Fax: 314-362-2244 Email: brodyd@neuro.wustl.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. These results demonstrate that DTI is able to detect axonal injury, and support the hypothesis that DTI may be more sensitive than conventional imaging methods for this purpose. NIH Public Access

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 77%

Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Donald

Dikranian

Song

et al. 2007

Experimental Neurology

273

209

View full text Add to dashboard Cite

show abstract

“…(Strich, 1956(Strich, , 1961Nevin, 1967;Oehmichen et al, 2003). Another issue is whether pericontusional axonal injury (Strich, 1961;Cervos-Navarro and Lafuente, 1991; differs fundamentally from diffuse axonal injury not associated with contusion (Adams et al, 1977(Adams et al, , 1982Vanezis et al, 1987;Graham et al, 1995;Geddes et al, 1997). The controlled cortical impact model used in this study produces a central contusion and surrounding pericontusional axonal injury.…”

Section: Discussionmentioning

confidence: 98%

Diffusion Tensor Imaging Reliably Detects Experimental Traumatic Axonal Injury and Indicates Approximate Time of Injury

Donald¹,

Dikranian²,

Bayly³

et al. 2007

J. Neurosci.

392

337

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Traumatic axonal injury (TAI) may contribute greatly to neurological impairments after traumatic brain injury, but it is difficult to assess with conventional imaging. We quantitatively compared diffusion tensor imaging (DTI) signal abnormalities with histological and electron microscopic characteristics of pericontusional TAI in a mouse model. Two DTI parameters, relative anisotropy and axial diffusivity, were significantly reduced 6 h to 4 d after trauma, corresponding to relatively isolated axonal injury. One to 4 weeks after trauma, relative anisotropy remained decreased, whereas axial diffusivity "pseudo-normalized" and radial diffusivity increased. These changes corresponded to demyelination, edema, and persistent axonal injury. At every time point, DTI was more sensitive to injury than conventional magnetic resonance imaging, and relative anisotropy distinguished injured from control mice with no overlap between groups. Remarkably, DTI changes strongly predicted the approximate time since trauma. These results provide an important validation of DTI for pericontusional TAI and suggest novel clinical and forensic applications.

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“…2 The pathophysiology of cerebral contusions is characterized by complex regional and temporal changes of cerebral blood flow and metabolism, 3,4 disruption of the blood brain barrier resulting in brain edema formation, 5 and cell death signaling, 6 -8 finally leading to progressive neuronal cell death in pericontusional tissue (ie, the traumatic penumbra). 9 The macroscopic manifestation of pericontusional cell death is a delayed increase of contusion volume over time, 10 a finding termed "secondary contusion expansion," and recently characterized experimentally in detail. 11 The ultimate steps leading to delayed cell death in pericontusional tissue are initiated by a combination of multiple mechanisms, such as over-activation of glutamate receptors, 12 free radical-mediated membrane damage, 13 nuclear translocation of transcription factors, tors, 15 and activation of apoptosis-like cell death signaling pathways.…”

Section: Traumatic Brain Injury (Tbi) Consists Of Two Phasesmentioning

confidence: 99%

Causal Role of Apoptosis-Inducing Factor for Neuronal Cell Death Following Traumatic Brain Injury

Slemmer

Zhu

Landshamer³

et al. 2008

The American Journal of Pathology

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Traumatic brain injury (TBI) consists of two phases:an immediate phase in which damage is caused as a direct result of the mechanical impact; and a late phase of altered biochemical events that results in delayed tissue damage and is therefore amenable to therapeutic treatment. Because the molecular mechanisms of delayed post-traumatic neuronal cell death are still poorly understood, we investigated whether apoptosis-inducing factor (AIF), a pro-apoptotic mitochondrial molecule and the key factor in the caspase-independent, cell death signaling pathway, plays a causal role in neuronal death following TBI. Using an in vitro model of neuronal stretch injury, we demonstrated that AIF translocated from mitochondria to the nucleus of neurons displaying axonal disruption, chromatin condensation, and nuclear pyknosis in a caspase-independent manner, whereas astrocytes remained unaffected. Similar findings were observed following experimental TBI in mice, where AIF translocation to the nucleus coincided with delayed neuronal cell death in both cortical and hippocampal neurons. Down-regulation of AIF in vitro by siRNA significantly reduced stretch-induced neuronal cell death by 67%, a finding corroborated in vivo using AIF-deficient harlequin mutant mice, where secondary contusion expansion was significantly reduced by 44%. Hence, our current findings demonstrate that caspase-independent, AIF-mediated signaling pathways significantly contribute to post-traumatic neuronal cell death and may therefore represent novel therapeutic targets for the treatment of TBI. (Am J Pathol

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Traumatic brain injuries: structural changes

Cited by 90 publications

References 42 publications

Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Diffusion Tensor Imaging Reliably Detects Experimental Traumatic Axonal Injury and Indicates Approximate Time of Injury

Causal Role of Apoptosis-Inducing Factor for Neuronal Cell Death Following Traumatic Brain Injury

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