Journal of neurotrauma
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Journal of neurotrauma · Aug 2005
Slow, medium, or fast re-warming following post-traumatic hypothermia therapy? An ultrastructural perspective.
It was hypothesized that rapid rather than slow re-warming following traumatic brain injury (TBI) and short-term hypothermia results in secondary, ultrastructural pathology. After stretch injury to the right optic nerve, adult guinea pigs were randomly allocated to one of six experimental groups. Either (1) sham (all procedures but not stretch-injured; n = 4); injured and (2) maintained at normal temporalis core temperature (38.5 degrees C) for 8 hours (n = 6); (3) cooled rapidly to 32.5 degrees C (temporalis temperature), maintained for 4 h and re-warmed to 38.5 degrees C at 1 degrees C rise every 10 min (fast; n = 6); (4) cooled and re-warmed at 1 degrees C rise every 20 min (medium; n = 6); (5) cooled and rewarmed at 1 degrees C rise every 40 min (slow; n = 6) before being killed 8 h after injury; and (6) uninjured animals (n = 6) cooled to 32.5 degrees C for 4 h and then re-warmed at 1 degrees C every 10 min before killing 4 h later. ⋯ The number of MT was reduced to 40% of control values, NFs were increased but were not compacted after medium rate re-warming. Following slow re-warming the axonal cytoskeleton did not differ from that in control animals. It is concluded that re-warming faster than 1 degrees C every 40 min following mild post-traumatic hypothermia induces secondary axonal pathology.
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Journal of neurotrauma · Aug 2005
Shedding of tumor necrosis factor type 1 receptor after experimental spinal cord injury.
In a number of stress conditions, the biological effects of tumor necrosis factor-alpha (TNF-alpha), such as the induction of neuronal apoptosis, are presumably attenuated by the soluble fragments of TNF receptors (sTNFRs). Within 1 h after spinal cord injury, increased synthesis and/or secretion of TNF-alpha is detectable at the injury site. However, the shedding of ectodomains of TNFRs in the traumatized spinal cord has not yet been reported. ⋯ Unlike sTNFR1, the levels of sTNFR2 in the CSF were unchanged at any time point post-ASCI. The increased shedding of TNFR1 was confirmed by Western blotting. It is concluded that the shedding of TNFR1 receptor may represent an important post-traumatic physiological response aimed at reducing the proapoptotic effect of TNF-alpha.
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Spinal cord injury (SCI) releases a cascade of events that leads to the onset of an inhibitory milieu for axonal regeneration. Some of these changes result from the presence of repulsive factors that may restrict axonal outgrowth after trauma. The Eph receptor tyrosine kinase (RTK) family has emerged as a key repellent cue known to be involved in neurite outgrowth, synapse formation, and axonal pathfinding during development. ⋯ In control animals, EphA3 immunoreactivity was observed in motor neurons of the ventral horn but not in lesioned animals. In addition, GFAP-positive cells were visualized in the ventral region of injured white matter. These results suggest that upregulation of EphA3 in reactive astrocytes may contribute to the repulsive environment for neurite outgrowth and may be involved in the pathophysiology generated after SCI.
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Journal of neurotrauma · Aug 2005
Diffusion-weighted imaging of edema following traumatic brain injury in rats: effects of secondary hypoxia.
Hypoxia and edema are frequent and serious complications of traumatic brain injury (TBI). Therefore, we examined the effects of hypoxia on edema formation after moderate lateral fluid percussion (LFP) injury using NMR diffusion-weighted imaging (DWI). Adult Sprague-Dawley rats were separated into four groups: sham uninjured (S), hypoxia alone (H), trauma alone (T), and trauma and hypoxia (TH). ⋯ TBI resulted in an early decrease in ADC values indicating cytotoxic edema in the cortex that was followed at 1 week by an increase in the ADC that was associated with decreased tissue cellularity. Histopathology corresponded well to the regions of brain injury and edema visualized by T2 and DWI procedures. Overall, the addition of hypoxia to brain injury resulted in a small increase in the magnitude of edema in hippocampus and cortex over that seen with trauma alone.
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Journal of neurotrauma · Aug 2005
Cell adhesion molecule l1-transfected embryonic stem cells with enhanced survival support regrowth of corticospinal tract axons in mice after spinal cord injury.
Previous studies have indicated that the cell adhesion molecule L1 enhances neuronal survival and neurite outgrowth. L1-mediated promotion of neurite outgrowth has been shown to occur also in an inhibitory environment not only in vitro, but also in vivo. To further investigate the effects of L1 in spinal cord injury, we transfected embryonic stem cells with a plasmid encoding the full-length mouse L1 molecule under the control of PGK promoter. ⋯ Anterogradely labeled corticospinal tract axons showed interdigitation with L1-transfected embryonic stem cells and, in contrast to non-transfected stem cells, extended into the lesion site 1 month after transplantation and, in some cases, extended beyond it. Our observations encourage the use of L1-transfected embryonic stem cells that express L1 not only at the cell surface, but also as a soluble and secreted form. Their use could condition the inhibitory environment for homophilic L1-enhanced axon regrowth not only in spinal cord regeneration, but also in other lesion paradigms.