Journal of neurotrauma
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Journal of neurotrauma · Dec 2013
The complement terminal pathway is activated in focal penetrating but not in mild diffuse Traumatic Brain Injury.
The complement system plays an important role in the inflammatory response activated by many central nervous system disorders. However, its significance in traumatic diffuse traumatic axonal injury (TAI) is not fully known. Here we analyze the complement activity in two rat models of traumatic brain injury (TBI); a focal penetration injury (pen-TBI) and a rotational acceleration injury (rot-TBI) that leads to a mild TAI. ⋯ Our findings suggest that the terminal complement pathway is progressed to the formation of the C5b-9 membrane attack complex only in the penetrating TBI but not in isolated TAI model. This indicates that the complement activation does not lead to membrane-damaging effects and a subsequent secondary axotomy in TAI by the terminal complex C5b-9. The role of complement activation in TAI is unclear, but might indicate an alternative function following rot-TBI, such as opsonizing the synapses for elimination.
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Journal of neurotrauma · Dec 2013
Controlled cortical impact results in an extensive loss of dendritic spines that is not mediated by injury-induced amyloid-beta accumulation.
The clinical manifestations that occur after traumatic brain injury (TBI) include a wide range of cognitive, emotional, and behavioral deficits. The loss of excitatory synapses could potentially explain why such diverse symptoms occur after TBI, and a recent preclinical study has demonstrated a loss of dendritic spines, the postsynaptic site of the excitatory synapse, after fluid percussion injury. The objective of this study was to determine if controlled cortical impact (CCI) also resulted in dendritic spine retraction and to probe the underlying mechanisms of this spine loss. ⋯ To determine if Aβ contributes to spine loss after brain injury, we administered a γ-secretase inhibitor LY450139 after TBI. We found that while LY450139 administration could attenuate the TBI-induced increase in Aβ, it had no effect on dendritic spine loss after TBI. We conclude that the acute, global loss of dendritic spines after TBI is independent of γ-secretase activity or TBI-induced Aβ accumulation.
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Journal of neurotrauma · Dec 2013
White Matter/Gray Matter Contrast Changes in Chronic and Diffuse Traumatic Brain Injury.
Signal-intensity contrast of T1-weighted magnetic resonance imaging scans has been associated with tissue integrity and reported as a sign of neurodegenerative changes in diseases such as Alzheimer's disease. After severe traumatic brain injury (TBI), progressive structural changes occur in white (WM) and gray matter (GM). In the current study, we assessed the signal-intensity contrast of GM and WM in patients with diffuse TBI in the chronic stage to (1) characterize the regional pattern of WM/GM changes in intensity contrast associated with traumatic axonal injury, (2) evaluate possible associations between this measure and diffusion tensor image (DTI)/fractional anisotropy (FA) for detecting WM damage, and (3) investigate the correlates of both measures with cognitive outcomes. ⋯ Global FA values obtained from DTI correlated with the intensity contrast of all associative cerebral regions. WM/GM contrast correlated with memory functions, whereas FA global values correlated with tests measuring memory and mental processing speed. In conclusion, tissue-contrast intensity is a very sensitive measure for detecting structural brain damage in chronic, severe and diffuse TBI, but is less sensitive than FA for reflecting neuropsychological sequelae, such as impaired mental processing speed.