Journal of neurotrauma
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Journal of neurotrauma · Jun 2011
Time-dependent changes in serum biomarker levels after blast traumatic brain injury.
Neuronal and glial proteins detected in the peripheral circulating blood after injury can reflect the extent of the damage caused by blast traumatic brain injury (bTBI). The temporal pattern of their serum levels can further predict the severity and outcome of the injury. As part of characterizing a large-animal model of bTBI, we determined the changes in the serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein (MBP), and neurofilament heavy chain (NF-H). ⋯ However, serum NF-H levels increased in a unique, rapid manner, peaking at 6 h post-injury only in animals exposed to severe blast with poor clinical and pathological outcomes. We conclude that the sudden increase in serum NF-H levels following bTBI may be a useful indicator of injury severity. If additional studies verify our findings, the observed early peak of serum NF-H levels can be developed into a useful diagnostic tool for predicting the extent of damage following bTBI.
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Journal of neurotrauma · Jun 2011
Sustained survival and maturation of adult neural stem/progenitor cells after transplantation into the injured brain.
Multipotent neural stem/progenitor cells (NS/NPCs) that are capable of generating neurons and glia offer enormous potential for treating neurological diseases. Adult NS/NPCs that reside in the mature mammalian brain can be isolated and expanded in vitro, and could be a potential source for autologous transplantation to replace cells lost to brain injury or disease. When these cells are transplanted into the normal brain, they can survive and become region-specific cells. ⋯ Many cells migrated out of the injection site into surrounding areas expressing astrocyte or oligodendrocyte markers. Whole cell patch-clamp recording at 4 weeks showed that transplanted cells possessed typical mature glial cell properties. These data demonstrate that adult NS/NPCs can survive in an injured heterotypic environment for an extended period and become functional cells.
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Journal of neurotrauma · Jun 2011
Chronic swelling and abnormal myelination during secondary degeneration after partial injury to a central nervous system tract.
Secondary degeneration is a serious consequence of traumatic injury to the central nervous system (CNS) and involves the progressive loss of neurons and function. However, while disruption to myelin has been observed in spared axons, the ultrastructural abnormalities that occur in myelin and axons spatially separated from the primary injury and susceptible exclusively to secondary degeneration are unknown. We used a model of secondary degeneration in which the dorsal aspect of rat optic nerve (ON) was transected leaving the central/ventral ON undamaged, but vulnerable to secondary degeneration. ⋯ Myelin basic protein immunoreactivity and fluoromyelin staining were also significantly reduced. Within four subpopulations of abnormally-myelinated axons, there was: no change in lightly-myelinated axons; an increase in axons with excessive myelination (at 1 month); and an increase in the density of axons with partial and fully-decompacted myelin (at 3 months, p ≤ 0.05). Chronic axon swelling and myelin sheath compaction defects are features of secondary degeneration, and may contribute to the reported loss of ON function following partial transection.
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Journal of neurotrauma · Jun 2011
Comparative StudyDifferential effects of low versus high amounts of weight supported treadmill training in spinally transected rats.
Intensive weight-supported treadmill training (WSTT) improves locomotor function following spinal cord injury. Because of a number of factors, undergoing intensive sessions of training may not be feasible. Whether reduced amounts of training are sufficient to enhance spinal plasticity to a level that is necessary for improving function is not known. ⋯ Synaptophysin expression, but not BDNF or TrkB expression was correlated with the recovery of stepping function. These findings suggested that a large amount of weight-supported treadmill training was necessary for restoring synaptic connections to motor neurons within the locomotor generating circuitry. Although a large amount of training was best for recovery, small amounts of training were associated with incremental gains in function and increased BDNF levels.
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Journal of neurotrauma · Jun 2011
Delayed intrathecal delivery of RhoA siRNA to the contused spinal cord inhibits allodynia, preserves white matter, and increases serotonergic fiber growth.
RhoA is a key regulator of the actin cytoskeleton that is upregulated after spinal cord injury (SCI). We analyzed different methods for siRNA delivery and developed siRNAs targeting RhoA (siRhoA) for SCI treatment. Cy 3.5-labeled siRNA delivered at the time of SCI yielded fluorescence in several cell types in the injury site. ⋯ Histological analysis at 8 weeks showed significant improvement in white matter sparing with siRhoA compared to control siRNA. siRhoA treatment also resulted in less accumulation of ED1+macrophages, increased PKC-γ immunoreactivity in the corticospinal tract rostral to the injury site, and increased serotonergic fiber growth 12 mm caudal to the contusion site. The ability of siRhoA to preserve white matter and promote serotonergic axonal regrowth caudal to the injury site is likely to suppress allodynia. This provides justification for considering clinical development of RhoA inhibitors to treat SCI sub-acutely to reduce allodynia, which occurs frequently in SCI patients.