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David L Brody - One of the best experts on this subject based on the ideXlab platform.
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Experimental subarachnoid haemorrhage results in multifocal Axonal Injury.
Brain : a journal of neurology, 2015Co-Authors: Terrance T Kummer, Sandra Magnoni, Christine L Macdonald, Krikor Dikranian, Eric Milner, James Sorrell, Valeria Conte, Joey J Benetatos, Gregory J Zipfel, David L BrodyAbstract:The great majority of acute brain Injury results from trauma or from disorders of the cerebrovasculature, i.e. ischaemic stroke or haemorrhage. These injuries are characterized by an initial insult that triggers a cascade of injurious cellular processes. The nature of these processes in spontaneous intracranial haemorrhage is poorly understood. Subarachnoid haemorrhage, a particularly deadly form of intracranial haemorrhage, shares key pathophysiological features with traumatic brain Injury including exposure to a sudden pressure pulse. Here we provide evidence that Axonal Injury, a signature characteristic of traumatic brain Injury, is also a prominent feature of experimental subarachnoid haemorrhage. Using histological markers of membrane disruption and cytoskeletal Injury validated in analyses of traumatic brain Injury, we show that Axonal Injury also occurs following subarachnoid haemorrhage in an animal model. Consistent with the higher prevalence of global as opposed to focal deficits after subarachnoid haemorrhage and traumatic brain Injury in humans, Axonal Injury in this model is observed in a multifocal pattern not limited to the immediate vicinity of the ruptured artery. Ultrastructural analysis further reveals characteristic Axonal membrane and cytoskeletal changes similar to those associated with traumatic Axonal Injury. Diffusion tensor imaging, a translational imaging technique previously validated in traumatic Axonal Injury, from these same specimens demonstrates decrements in anisotropy that correlate with histological Axonal Injury and functional outcomes. These radiological indicators identify a fibre orientation-dependent gradient of Axonal Injury consistent with a barotraumatic mechanism. Although traumatic and haemorrhagic acute brain Injury are generally considered separately, these data suggest that a signature pathology of traumatic brain Injury-Axonal Injury-is also a functionally significant feature of subarachnoid haemorrhage, raising the prospect of common diagnostic, prognostic, and therapeutic approaches to these conditions.
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Experimental subarachnoid haemorrhage results in multifocal Axonal Injury
Brain, 2015Co-Authors: Terrance T Kummer, Sandra Magnoni, Krikor Dikranian, James Sorrell, Valeria Conte, Joey J Benetatos, Gregory J Zipfel, Christine Macdonald, Eric C. B. Milner, David L BrodyAbstract:The great majority of acute brain Injury results from trauma or from disorders of the cerebrovasculature, i.e. ischaemic stroke or haemorrhage. These injuries are characterized by an initial insult that triggers a cascade of injurious cellular processes. The nature of these processes in spontaneous intracranial haemorrhage is poorly understood. Subarachnoid haemorrhage, a particularly deadly form of intracranial haemorrhage, shares key pathophysiological features with traumatic brain Injury including exposure to a sudden pressure pulse. Here we provide evidence that Axonal Injury, a signature characteristic of traumatic brain Injury, is also a prominent feature of experimental subarachnoid haemorrhage. Using histological markers of membrane disruption and cytoskeletal Injury validated in analyses of traumatic brain Injury, we show that Axonal Injury also occurs following subarachnoid haemorrhage in an animal model. Consistent with the higher prevalence of global as opposed to focal deficits after subarachnoid haemorrhage and traumatic brain Injury in humans, Axonal Injury in this model is observed in a multifocal pattern not limited to the immediate vicinity of the ruptured artery. Ultrastructural analysis further reveals characteristic Axonal membrane and cytoskeletal changes similar to those associated with traumatic Axonal Injury. Diffusion tensor imaging, a translational imaging technique previously validated in traumatic Axonal Injury, from these same specimens demonstrates decrements in anisotropy that correlate with histological Axonal Injury and functional outcomes. These radiological indicators identify a fibre orientation-dependent gradient of Axonal Injury consistent with a barotraumatic mechanism. Although traumatic and haemorrhagic acute brain Injury are generally considered separately, these data suggest that a signature pathology of traumatic brain Injury—Axonal Injury—is also a functionally significant feature of subarachnoid haemorrhage, raising the prospect of common diagnostic, prognostic, and therapeutic approaches to these conditions. * Abbreviations : DTI : diffusion tensor imaging SAH : subarachnoid haemorrhage TBI : traumatic brain Injury
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detection of traumatic Axonal Injury with diffusion tensor imaging in a mouse model of traumatic brain Injury
Experimental Neurology, 2007Co-Authors: Mac C Donald, Krikor Dikranian, David L Brody, Shengkwei Song, Philip V Bayly, David M HoltzmanAbstract: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 h and 24 h 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 detectable on all MRI sequences. Significant correlations were found between changes in relative anisotropy and the density of APP stained 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. 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.
Nigel R. Jones - One of the best experts on this subject based on the ideXlab platform.
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Impact mechanics and Axonal Injury in a sheep model.
Journal of neurotrauma, 2003Co-Authors: Rob Anderson, Peter C. Blumbergs, Christopher J. Brown, A. Jack Mclean, Nigel R. JonesAbstract:This paper describes a biomechanical study of Axonal Injury due to a blunt impact to the head. The aim of the experimental model was to produce Axonal Injury analogous to that seen in human trauma while measuring the dynamics of the impact and the subsequent kinematics of the head. These measurements were made in a way to facilitate the simulation of these experiments using the finite element method. Sheep were anaesthetised and ventilated, and subjected to a single impact to the lateral aspect of their skull. The impact force was measured throughout the duration of the impact and the kinematics of the head was measured using a novel implementation of a nine-accelerometer array. The Axonal Injury was identified using amyloid precursor protein (APP) as a marker, intensified using antigen retrieval techniques. Axonal Injury was consistently produced in all animals. Commonly injured regions included the sub-cortical and deep white matter, and the periventricular white matter surrounding the lateral ventricle...
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Topography and severity of Axonal Injury in human spinal cord trauma using amyloid precursor protein as a marker of Axonal Injury.
Spine, 2000Co-Authors: Ryan Cornish, Peter C. Blumbergs, Grace Scott, Jim Manavis, Nigel R. Jones, Peter L. ReillyAbstract:STUDY DESIGN Axonal Injury was examined in 18 human cases of acute spinal cord compression using amyloid precursor protein as a marker of AI. OBJECTIVES To topographically map and semiquantitate Axonal Injury in spinal cord compression of sufficient severity to produce para- or quadriplegia. SUMMARY OF BACKGROUND DATA Amyloid precursor protein is carried along the axon by fast axoplasmic transport and has been extensively used as a marker of traumatic Axonal Injury. METHODS The study group comprised 18 cases of spinal cord compression (17 due to fracture dislocation of the vertebral column and 1 iatrogenic compression from Harrington rods) and two normal control. All the cords were examined according to a standard protocol, and at least 10 segmental levels were immunostained using a monoclonal antibody to amyloid precursor protein and immunopositive AI was semiquantitated using a grading system to provide the Axonal Injury severity score (AISS). The focal Injury at the site of cord compression (haemorrhage, haemorrhagic necrosis, ischaemic necrosis) was also semiquantitated to provide the focal Injury area score (FIAS). AI occurring around the site of focal compression (focal Axonal Injury severity score or FAISS) was distinguished from AI distant to the focal Injury (nonfocal Axonal Injury severity score or NFAISS). RESULTS All 18 cases showed widespread amyloid precursor protein immunoreactive Axonal Injury and the AISS ranged from 28 to 60%. In all cases, the FAISS was greater than the NFAISS and there was a statistically significant relationship between the AISS and the FIAS. CONCLUSION Acute spinal cord compression of sufficient severity to produce permanent paralysis causes widespread Axonal damage that is maximal at the site of compression but also present throughout the length of the cord in segments far distant from the site of the focal Injury.
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Biomechanics of a sheep model of Axonal Injury
1997Co-Authors: Rob Anderson, Peter C. Blumbergs, Grace Scott, Christopher J. Brown, A. Jack Mclean, John W. Finnie, Nigel R. JonesAbstract:The aim of this project was to investigate the feasibility of using an animal model of Axonal Injury to study the biomechanics of Injury. The model utilises anaesthetised sheep that are mechanically ventilated and stabilised before being subjected to a single lateral impact from a captive bolt gun. The impact force was measured using a load cell mounted in the striker, and the resulting head acceleration was measured by means of a 9-accelerometer array which was rigidly mounted to the head of the sheep. Head kinematics were transformed to anatomical coordinates using stereo-radiography. High speed cine film (1000 fps) was used for the visualisation of gross head motion. After impact, each animal was allowed to survive for a predetermined period during which anaesthesia was maintained. A complement of physiological monitors was used to measure the physiological state of the animal at all times during the experiment. In one experiment, hypoxia was induced after the physical insult. After the survival period, the animal was sacrificed and the brain removed for histological processing. The brain was sectioned, processed and examined for Axonal Injury using the presence of amyloid precursor protein (APP) as an indicator of Injury. The distribution of Axonal Injury in serial sections of the brain was mapped and quantified. Five experiments, displaying a range of Injury responses, are reported on in the paper. In the future, the model will be used to study the biomechanics of Axonal Injury. (A) For the covering abstract of the conference see ITRD E203597.
Evelyn E. Babcock - One of the best experts on this subject based on the ideXlab platform.
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Diffusion Tensor Tractography of Traumatic Diffuse Axonal Injury
Archives of neurology, 2008Co-Authors: Jun Yi Wang, Khamid Bakhadirov, Michael D. Devous, Hervé Abdi, Roderick W Mccoll, Carol Moore, Carlos Marquez De La Plata, Kan Ding, Anthony R Whittemore, Evelyn E. BabcockAbstract:Background Diffuse Axonal Injury is a common consequence of traumatic brain Injury that frequently involves the parasagittal white matter, corpus callosum, and brainstem. Objective To examine the potential of diffusion tensor tractography in detecting diffuse Axonal Injury at the acute stage of Injury and predicting long-term functional outcome. Design Tract-derived fiber variables were analyzed to distinguish patients from control subjects and to determine their relationship to outcome. Setting Inpatient traumatic brain Injury unit. Patients From 2005 to 2006, magnetic resonance images were acquired in 12 patients approximately 7 days after Injury and in 12 age- and sex-matched controls. Main Outcome Measures Six fiber variables of the corpus callosum, fornix, and peduncular projections were obtained. Glasgow Outcome Scale–Extended scores were assessed approximately 9 months after Injury in 11 of the 12 patients. Results At least 1 fiber variable of each region showed diffuse Axonal Injury–associated alterations. At least 1 fiber variable of the anterior body and splenium of the corpus callosum correlated significantly with the Glasgow Outcome Scale–Extended scores. The predicted outcome scores correlated significantly with actual scores in a mixed-effects model. Conclusion Diffusion tensor tractography–based quantitative analysis at the acute stage of Injury has the potential to serve as a valuable biomarker of diffuse Axonal Injury and predict long-term outcome.
Peter C. Blumbergs - One of the best experts on this subject based on the ideXlab platform.
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Impact mechanics and Axonal Injury in a sheep model.
Journal of neurotrauma, 2003Co-Authors: Rob Anderson, Peter C. Blumbergs, Christopher J. Brown, A. Jack Mclean, Nigel R. JonesAbstract:This paper describes a biomechanical study of Axonal Injury due to a blunt impact to the head. The aim of the experimental model was to produce Axonal Injury analogous to that seen in human trauma while measuring the dynamics of the impact and the subsequent kinematics of the head. These measurements were made in a way to facilitate the simulation of these experiments using the finite element method. Sheep were anaesthetised and ventilated, and subjected to a single impact to the lateral aspect of their skull. The impact force was measured throughout the duration of the impact and the kinematics of the head was measured using a novel implementation of a nine-accelerometer array. The Axonal Injury was identified using amyloid precursor protein (APP) as a marker, intensified using antigen retrieval techniques. Axonal Injury was consistently produced in all animals. Commonly injured regions included the sub-cortical and deep white matter, and the periventricular white matter surrounding the lateral ventricle...
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Topography and severity of Axonal Injury in human spinal cord trauma using amyloid precursor protein as a marker of Axonal Injury.
Spine, 2000Co-Authors: Ryan Cornish, Peter C. Blumbergs, Grace Scott, Jim Manavis, Nigel R. Jones, Peter L. ReillyAbstract:STUDY DESIGN Axonal Injury was examined in 18 human cases of acute spinal cord compression using amyloid precursor protein as a marker of AI. OBJECTIVES To topographically map and semiquantitate Axonal Injury in spinal cord compression of sufficient severity to produce para- or quadriplegia. SUMMARY OF BACKGROUND DATA Amyloid precursor protein is carried along the axon by fast axoplasmic transport and has been extensively used as a marker of traumatic Axonal Injury. METHODS The study group comprised 18 cases of spinal cord compression (17 due to fracture dislocation of the vertebral column and 1 iatrogenic compression from Harrington rods) and two normal control. All the cords were examined according to a standard protocol, and at least 10 segmental levels were immunostained using a monoclonal antibody to amyloid precursor protein and immunopositive AI was semiquantitated using a grading system to provide the Axonal Injury severity score (AISS). The focal Injury at the site of cord compression (haemorrhage, haemorrhagic necrosis, ischaemic necrosis) was also semiquantitated to provide the focal Injury area score (FIAS). AI occurring around the site of focal compression (focal Axonal Injury severity score or FAISS) was distinguished from AI distant to the focal Injury (nonfocal Axonal Injury severity score or NFAISS). RESULTS All 18 cases showed widespread amyloid precursor protein immunoreactive Axonal Injury and the AISS ranged from 28 to 60%. In all cases, the FAISS was greater than the NFAISS and there was a statistically significant relationship between the AISS and the FIAS. CONCLUSION Acute spinal cord compression of sufficient severity to produce permanent paralysis causes widespread Axonal damage that is maximal at the site of compression but also present throughout the length of the cord in segments far distant from the site of the focal Injury.
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Axonal Injury in falls
Journal of neurotrauma, 1997Co-Authors: A. Abou-hamden, Peter C. Blumbergs, Grace Scott, Jim Manavis, H. Wainwright, Norman Jones, J McleanAbstract:ABSTRACT Amyloid precursor protein (APP) immunocytochemistry was used as a marker for Axonal Injury (AI) in a series of 16 cases of head trauma associated with fatal falls. Nine cases were falls from not more than the person's own height (falls from ≤ own height) and seven cases were falls from a distance greater than the person's own height (falls from > own height). AI was recorded on a series of line diagrams of standard brain sections divided into 116 sectors. AI around focal lesions (infarcts, hemorrhages, contusions) was distinguished from nonfocal Axonal Injury that was distant from any focal area of damage. The percentage of sectors showing focal AI provided the Focal Axonal Injury Score (FAIS) and the percentage showing nonfocal AI the Non-Focal Axonal Injury Score (NFAIS). The FAIS is a measure of secondary AI and the NFAIS of diffuse Axonal Injury (DAI). The percentage of sectors involved with AI (focal and nonfocal) provided the cumulative Axonal Injury Score (AIS). A semiquantitative grading ...
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Biomechanics of a sheep model of Axonal Injury
1997Co-Authors: Rob Anderson, Peter C. Blumbergs, Grace Scott, Christopher J. Brown, A. Jack Mclean, John W. Finnie, Nigel R. JonesAbstract:The aim of this project was to investigate the feasibility of using an animal model of Axonal Injury to study the biomechanics of Injury. The model utilises anaesthetised sheep that are mechanically ventilated and stabilised before being subjected to a single lateral impact from a captive bolt gun. The impact force was measured using a load cell mounted in the striker, and the resulting head acceleration was measured by means of a 9-accelerometer array which was rigidly mounted to the head of the sheep. Head kinematics were transformed to anatomical coordinates using stereo-radiography. High speed cine film (1000 fps) was used for the visualisation of gross head motion. After impact, each animal was allowed to survive for a predetermined period during which anaesthesia was maintained. A complement of physiological monitors was used to measure the physiological state of the animal at all times during the experiment. In one experiment, hypoxia was induced after the physical insult. After the survival period, the animal was sacrificed and the brain removed for histological processing. The brain was sectioned, processed and examined for Axonal Injury using the presence of amyloid precursor protein (APP) as an indicator of Injury. The distribution of Axonal Injury in serial sections of the brain was mapped and quantified. Five experiments, displaying a range of Injury responses, are reported on in the paper. In the future, the model will be used to study the biomechanics of Axonal Injury. (A) For the covering abstract of the conference see ITRD E203597.
Yoshinobu Kimura - One of the best experts on this subject based on the ideXlab platform.
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Axonal Injury in experimental herpes simplex encephalitis.
Brain research, 2005Co-Authors: Isamu Mori, Fumi Goshima, Terukazu Mizuno, Yoshinori Imai, Shinichi Kohsaka, Hiroyasu Ito, Naoki Koide, Tomoaki Yoshida, Takashi Yokochi, Yoshinobu KimuraAbstract:Using beta-amyloid precursor protein immunolabeling, we have detected Axonal Injury in experimental herpes simplex encephalitis. beta-amyloid precursor protein-specific signals were found in the mouse brain as either puncta or axon-like structures. They appeared where infected neurons were undergoing apoptosis and Iba1-immunopositive microglia transformed themselves into macrophages. These results show, for the first time, that Axonal Injury, i.e., functional disturbance of the fast Axonal transport, can take place during the course of acute viral encephalitis.
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Axonal Injury in experimental herpes simplex encephalitis
Brain Research, 2005Co-Authors: Isamu Mori, Fumi Goshima, Terukazu Mizuno, Yoshinori Imai, Shinichi Kohsaka, Hiroyasu Ito, Naoki Koide, Tomoaki Yoshida, Takashi Yokochi, Yoshinobu KimuraAbstract:Abstract Using β-amyloid precursor protein immunolabeling, we have detected Axonal Injury in experimental herpes simplex encephalitis. β-amyloid precursor protein-specific signals were found in the mouse brain as either puncta or axon-like structures. They appeared where infected neurons were undergoing apoptosis and Iba1-immunopositive microglia transformed themselves into macrophages. These results show, for the first time, that Axonal Injury, i.e., functional disturbance of the fast Axonal transport, can take place during the course of acute viral encephalitis.