Journal of neurotrauma
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Journal of neurotrauma · Jun 2013
Beneficial function of cell division cycle 2 activity in astrocytes on axonal regeneration after spinal cord injury.
Migrating activity of reactive astrocytes induced after spinal cord injury (SCI) controls glial scar formation by limiting inflammatory responses around the injury area, and, therefore, can be beneficial for regenerative responses of spinal axons. Recently, we found that cell division cycle 2 (cdc2) activity in primary astrocytes facilitated neurite outgrowth of co-cultured neurons. Here, we investigated the effects of cdc2 activity on regenerative processes in vivo after SCI. ⋯ After SCI, regenerative responses of anterogradely labeled corticospinal tract (CST) axons were attenuated by purvalanol A treatment. Using the polymeric tube that was implanted into the spinal cord as a nerve guide conduit, we found that purvalanol A treatments reduced astrocyte migration into the tube graft and, in parallel, retarded the extension of spinal axons into the tube. These results suggest that astrocytes with cdc2 activity may play a permissive role in mediating regrowth of spinal axons after lesion.
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Journal of neurotrauma · Jun 2013
Acute delivery of EphA4-Fc improves functional recovery after contusive spinal cord injury in rats.
Blocking the action of inhibitory molecules at sites of central nervous system injury has been proposed as a strategy to promote axonal regeneration and functional recovery. We have previously shown that genetic deletion or competitive antagonism of EphA4 receptor activity promotes axonal regeneration and functional recovery in a mouse model of lateral hemisection spinal cord injury. ⋯ Consistent with functional improvement, using high-resolution ex vivo magnetic resonance imaging at 16.4T, we found that rats treated with EphA4-Fc had a significantly increased cross-sectional area of the dorsal funiculus caudal to the injury epicenter compared with controls. Our findings indicate that EphA4-Fc promotes functional recovery following contusive spinal cord injury and provides further support for the therapeutic benefit of treatment with the competitive antagonist in acute cases of spinal cord injury.
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Journal of neurotrauma · Jun 2013
The influence of chronic cigarette smoking on neurocognitive recovery after mild traumatic brain injury.
The majority of the approximately 1.7 million civilians in the United States who seek emergency care for traumatic brain injury (TBI) are classified as mild (MTBI). Premorbid and comorbid conditions that commonly accompany MTBI may influence neurocognitive and functional recovery. This study assessed the influence of chronic smoking and hazardous alcohol consumption on neurocognitive recovery after MTBI. ⋯ Hazardous alcohol consumption was not significantly associated with change in any neurocognitive domain. For sMTBI, over the AP1-AP2 interval, greater lifetime duration of smoking and pack-years were related to significantly less improvement on multiple domains. Results suggest consideration of the effects of chronic cigarette smoking is necessary to understand the potential factors influencing neurocognitive recovery after MTBI.
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Journal of neurotrauma · Jun 2013
Screening of biochemical and molecular mechanisms of secondary injury and repair in the brain after experimental blast-induced traumatic brain injury in rats.
Abstract Explosive blast-induced traumatic brain injury (TBI) is the signature insult in modern combat casualty care and has been linked to post-traumatic stress disorder, memory loss, and chronic traumatic encephalopathy. In this article we report on blast-induced mild TBI (mTBI) characterized by fiber-tract degeneration and axonal injury revealed by cupric silver staining in adult male rats after head-only exposure to 35 psi in a helium-driven shock tube with head restraint. We now explore pathways of secondary injury and repair using biochemical/molecular strategies. ⋯ ATP was not depleted, and adenosine correlated with 2'-cyclic AMP (cAMP), and not 5'-cAMP. Our data reveal (1) gene-array alterations similar to disorders of memory processing and a marked astrocyte response, (2) OS, (3) neuroinflammation with a sustained chemokine response, and (4) adenosine production despite lack of energy failure-possibly resulting from metabolism of 2'-3'-cAMP. A robust biochemical/molecular response occurs after blast-induced mTBI, with the body protected from blast and the head constrained to limit motion.
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Dementia pugilistica (DP), a suite of neuropathological and cognitive function declines after chronic traumatic brain injury (TBI), is present in approximately 20% of retired boxers. Epidemiological studies indicate TBI is a risk factor for neurodegenerative disorders including Alzheimer disease (AD) and Parkinson disease (PD). Some biochemical alterations observed in AD and PD may be recapitulated in DP and other TBI persons. ⋯ In addition, the levels of brain-derived neurotrophic factor and the axonal transport proteins kinesin and dynein were substantially decreased in DP relative to NDC participants. Traumatic brain injury is a risk factor for dementia development, and our findings are consistent with permanent structural and functional damage in the cerebral cortex and white matter of boxers. Understanding the precise threshold of damage needed for the induction of pathology in DP and TBI is vital.