Axonal pathology in traumatic brain injury

Abstract

Over the past 70 years, diffuse axonal injury (DAI) has emerged as one of the most common and important pathological features of traumatic brain injury (TBI). Axons in the white matter appear to be especially vulnerable to injury due to the mechanical loading of the brain during TBI. As such, DAI has been found in all severities of TBI and may represent a key pathologic substrate of mild TBI (concussion). Pathologically, DAI encompasses a spectrum of effects from primary mechanical breaking of the axonal cytoskeleton, to transport interruption, swelling and proteolysis, through secondary physiological changes. Depending on the severity and extent of injury, these changes can manifest acutely as immediate loss of consciousness or confusion and persist as coma and/or cognitive dysfunction. In addition, recent evidence suggests that TBI may induce long-term neurodegenerative processes, such as insidiously progressive axonal pathology. Indeed, axonal degeneration has been found to continue even years after injury in humans, and appears to play a role in the development of Alzheimer’s disease-like pathological changes. Here we review the current understanding of DAI as a uniquely mechanical injury, its histopathological identification, and its acute and chronic pathogenesis following TBI.

Laquinimod attenuates inflammation by modulating macrophage functions in traumatic brain injury mouse model

“…Using immunohistochemistry technique, we evaluated axonal damage in the lesion ipsilateral corpus callosum and hippocampus. Consistent with previous studies [ 18 , 25 ], there was an increase in APP-positive profiles in the body of the corpus callosum as well as in hippocampus in the TBI-water group (Fig. 2 a).…”

Laquinimod attenuates inflammation by modulating macrophage functions in traumatic brain injury mouse model

“…Using immunohistochemistry technique, we evaluated axonal damage in the lesion ipsilateral corpus callosum and hippocampus. Consistent with previous studies [ 18 , 25 ], there was an increase in APP-positive profiles in the body of the corpus callosum as well as in hippocampus in the TBI-water group (Fig. 2 a).…”

SNTF immunostaining reveals previously undetected axonal pathology in traumatic brain injury

“…Consistent with previous examinations in both animal models and clinical DAI [23, 34, 35, 59], axonal pathology was observed at all time-points post-injury from 6-72 hours. Notably, while the distribution was the same at 6 hours post-injury, the extent of pathology was not as marked when compared to that following 48-72 hours survival.…”

Acute white matter changes following sport‐related concussion: A serial diffusion tensor and diffusion kurtosis tensor imaging study

“…Our DKTI findings are in contrast to some studies investigating sub-acute to chronic stage of mild TBI, which have reported decreased mean and radial kurtosis [Grossman et al, 2012[Grossman et al, , 2013Stokum et al, 2015]. This is possibly due to eventual axonal degeneration secondary to axonal beading [Buki and Povlishock, 2006;Johnson et al, 2013]. Additional work is needed to determine the relationship between the SRC recovery curve and patterns of disrupted kurtosis.…”

Laquinimod attenuates inflammation by modulating macrophage functions in traumatic brain injury mouse model

“…Using immunohistochemistry technique, we evaluated axonal damage in the lesion ipsilateral corpus callosum and hippocampus. Consistent with previous studies [ 18 , 25 ], there was an increase in APP-positive profiles in the body of the corpus callosum as well as in hippocampus in the TBI-water group (Fig. 2 a).…”

SNTF immunostaining reveals previously undetected axonal pathology in traumatic brain injury

“…Consistent with previous examinations in both animal models and clinical DAI [23, 34, 35, 59], axonal pathology was observed at all time-points post-injury from 6-72 hours. Notably, while the distribution was the same at 6 hours post-injury, the extent of pathology was not as marked when compared to that following 48-72 hours survival.…”

Acute white matter changes following sport‐related concussion: A serial diffusion tensor and diffusion kurtosis tensor imaging study

“…Our DKTI findings are in contrast to some studies investigating sub-acute to chronic stage of mild TBI, which have reported decreased mean and radial kurtosis [Grossman et al, 2012[Grossman et al, , 2013Stokum et al, 2015]. This is possibly due to eventual axonal degeneration secondary to axonal beading [Buki and Povlishock, 2006;Johnson et al, 2013]. Additional work is needed to determine the relationship between the SRC recovery curve and patterns of disrupted kurtosis.…”

Laquinimod attenuates inflammation by modulating macrophage functions in traumatic brain injury mouse model

“…Using immunohistochemistry technique, we evaluated axonal damage in the lesion ipsilateral corpus callosum and hippocampus. Consistent with previous studies [ 18 , 25 ], there was an increase in APP-positive profiles in the body of the corpus callosum as well as in hippocampus in the TBI-water group (Fig. 2 a).…”

SNTF immunostaining reveals previously undetected axonal pathology in traumatic brain injury

“…Consistent with previous examinations in both animal models and clinical DAI [23, 34, 35, 59], axonal pathology was observed at all time-points post-injury from 6-72 hours. Notably, while the distribution was the same at 6 hours post-injury, the extent of pathology was not as marked when compared to that following 48-72 hours survival.…”

Acute white matter changes following sport‐related concussion: A serial diffusion tensor and diffusion kurtosis tensor imaging study

“…Our DKTI findings are in contrast to some studies investigating sub-acute to chronic stage of mild TBI, which have reported decreased mean and radial kurtosis [Grossman et al, 2012[Grossman et al, , 2013Stokum et al, 2015]. This is possibly due to eventual axonal degeneration secondary to axonal beading [Buki and Povlishock, 2006;Johnson et al, 2013]. Additional work is needed to determine the relationship between the SRC recovery curve and patterns of disrupted kurtosis.…”