Journal of neurotrauma
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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
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
Remote brain network changes after unilateral cortical impact injury and their modulation by acetylcholinesterase inhibition.
We explored whether cerebral cortical impact injury (CCI) effects extend beyond direct lesion sites to affect remote brain networks, and whether acetylcholinesterase (AChE) inhibition elicits discrete changes in functional activation of motor circuits following CCI. Adult male rats underwent unilateral motor-sensory CCI or sham injury. Physostigmine (AChE inhibitor) or saline were administered subcutaneously continuously via implanted minipumps (1.6 micromoles/kg/day) for 3 weeks, followed by cerebral perfusion mapping during treadmill walking using [(14)C]-iodoantipyrine. ⋯ This phenomenon, augmented by physostigmine, may partially compensate motor deficits. FC decreased inter-hemispherically and in negative, but not positive, intra-hemispherical FC, and it was not affected by physostigmine. Circuit-based approaches into functional brain reorganization may inform future behavioral or molecular strategies to augment targeted neurorehabilitation.
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Journal of neurotrauma · Jun 2013
S100b as a prognostic biomarker in outcome prediction for patients with severe traumatic brain injury.
As an astrocytic protein specific to the central nervous system, S100b is a potentially useful marker in outcome prediction after traumatic brain injury (TBI). Some studies have questioned the validity of S100b, citing the extracerebral origins of the protein as reducing the specificity of the marker. This study evaluated S100b as a prognostic biomarker in adult subjects with severe TBI (sTBI) by comparing outcomes with S100b temporal profiles generated from both cerebrospinal fluid (CSF) (n = 138 subjects) and serum (n = 80 subjects) samples across a 6-day time course. ⋯ Possibly as a result of extracerebral sources of S100b in serum, as represented by high ISS scores (p = 0.032), temporal serum profiles were associated with acute mortality (p = 0.015). High CSF S100b levels were observed in women (p = 0.022) and older subjects (p = 0.004). Multivariate logistic regression confirmed CSF S100b profiles in predicting GOS and DRS and showed mean and peak serum S100b as acute mortality predictors after sTBI.
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Journal of neurotrauma · Jun 2013
The Glasgow Outcome at Discharge Scale: an inpatient assessment of disability after brain injury.
This study assesses the validity and reliability of the Glasgow Outcome at Discharge Scale (GODS), which is a tool that is designed to assess disability after brain injury in an inpatient setting. It is derived from the Glasgow Outcome Scale-Extended (GOS-E), which assesses disability in the community after brain injury. ⋯ In terms of predictive validity the GODS is highly associated with the GOS-E after discharge (Spearman correlation 0.512; 95% CI 0.281, 0.687), with the DRS, and with physical, fatigue, and social subscales of the SF-36. The GODS is recommended as an assessment tool for disability after brain injury pre-discharge and can be used in conjunction with the GOS-E to monitor disability between hospital and the community.