Journal of neurotrauma
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Journal of neurotrauma · Jun 2011
Comparative StudyLong-term outcomes after uncomplicated mild traumatic brain injury: a comparison with trauma controls.
The question as to whether mild traumatic brain injury (mTBI) results in persisting sequelae over and above those experienced by individuals sustaining general trauma remains controversial. This prospective study aimed to document outcomes 1 week and 3 months post-injury following mTBI assessed in the emergency department (ED) of a major adult trauma center. One hundred and twenty-three patients presenting with uncomplicated mTBI and 100 matched trauma controls completed measures of post-concussive symptoms and cognitive performance (Immediate Post-Concussion Assessment and Cognitive Testing battery; ImPACT) and pre-injury health-related quality of life (SF-36) in the ED. ⋯ There were no significant group differences in psychiatric function. However, the group with mild TBI was more likely to report ongoing memory and concentration problems in daily activities. Further investigation of factors associated with these ongoing problems is warranted.
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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
Reactive astrocytes inhibit the survival and differentiation of oligodendrocyte precursor cells by secreted TNF-α.
Axonal demyelination is a consistent pathological characteristic of spinal cord injury (SCI). Although an increased number of oligodendrocyte progenitor cells (OPCs) is observed in the injured spinal cord, they fail to convert into mature oligodendrocytes. However, little is known about the underlying mechanism. ⋯ When TNF-α or TNF-R1 was neutralized with antibody, the effect of reactive astrocyte-conditioned medium or recombinant TNF-α protein on OPC differentiation was markedly attenuated. In addition, reactive astrocyte-conditioned medium was also shown to induce OPC apoptosis. All these findings provide the first evidence that reactive astrocytes release TNF-α to inhibit OPC survival and prevent them from differentiating into mature oligodendrocytes, suggesting a mechanism for the failure of remyelination after SCI.
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Journal of neurotrauma · Jun 2011
Impact of cervical spine management brain injury on functional survival outcomes in comatose, blunt trauma patients with extremity movement and negative cervical spine CT: application of the Monte Carlo simulation.
Cervical spine (CS) magnetic resonance imaging (MRI) and collar use may prevent quadriplegia, yet create brain injury. We developed a computer model to assess the effect of CS management strategies on outcomes in comatose, blunt trauma patients with extremity movement and a negative CS CT scan. Strategies include early collar removal (ECR), ECR & MRI, late collar removal (LCR), and LCR & MRI. ⋯ Quality-Adjusted Life Months for Unstable, High-Risk, and Stable Patients are greater with ECR. LCR and MRI brain injury results in losses of functional survivorship that exceed those from quadriplegia. Model results suggest that early collar removal without cervical spine MRI is a reasonable, and likely the preferable, cervical spine management strategy for comatose, blunt trauma patients with extremity movement and a negative cervical spine CT scan.
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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.