Journal of neurotrauma
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Journal of neurotrauma · May 2009
Cerebral autoregulatory response depends on the direction of change in perfusion pressure.
The purpose of cerebral autoregulation is to keep cerebral blood flow constant during variations of cerebral perfusion pressure (CPP). Recently, the autoregulatory response was reported to be greater during arterial blood pressure (ABP) increase than during decrease following repeated induced changes in ABP in 14 brain-injured subjects. The goal of this study was to further investigate the asymmetry of autoregulation during spontaneous increases and decreases of CPP in a larger group of brain injury patients. ⋯ Despite this difference, upMx and downMx were strongly correlated with each other (R=0.82; p < 0.001). In conclusion, the autoregulatory response was significantly greater during increase than during decrease in CPP. The results may indicate non-linear behavior of cerebral autoregulation.
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Journal of neurotrauma · May 2009
Forced exercise as a rehabilitation strategy after unilateral cervical spinal cord contusion injury.
Evaluation of locomotor training after spinal cord injury (SCI) has primarily focused on hind limb recovery, with evidence of functional and molecular changes in response to exercise. Since trauma at a cervical (C) level is common in human SCI, we used a unilateral C4 contusion injury model in rats to determine whether forced exercise (Ex) would affect spinal cord biochemistry, anatomy, and recovery of fore and hind limb function. SCI was created with the Infinite Horizon spinal cord impactor device at C4 with a force of 200 Kdyne and a mean displacement of 1600-1800 microm in adult female Sprague-Dawley rats that had been acclimated to a motorized exercise wheel apparatus. ⋯ The BBB test showed no change with Ex at the end of the 8-week period, however hind limb grid performance was improved during weeks 2-4. Lesion size was not affected by Ex, but the presence of phagocytic and reactive glial cells was reduced with Ex as an intervention. These results suggest that Ex alone can influence the evolution of the injury and transiently improve fore and hind limb function during weeks 2-4 following a cervical SCI.
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Journal of neurotrauma · May 2009
A novel protein complex in membrane rafts linking the NR2B glutamate receptor and autophagy is disrupted following traumatic brain injury.
Hyperactivation of N-methyl-D-aspartate receptors (NRs) is associated with neuronal cell death induced by traumatic brain injury (TBI) and many neurodegenerative conditions. NR signaling efficiency is dependent on receptor localization in membrane raft microdomains. Recently, excitotoxicity has been linked to autophagy, but mechanisms governing signal transduction remain unclear. ⋯ Moderate TBI induced rapid recruitment and association of NR2B and pCaMKII to membrane rafts, and translocation of Beclin-1 out of membrane microdomains. Furthermore, TBI caused significant increases in expression of key autophagic proteins and morphological hallmarks of autophagy that were significantly attenuated by treatment with the NR2B antagonist Ro 25-6981. Thus, stimulation of autophagy by NR2B signaling may be regulated by redistribution of Beclin-1 in membrane rafts after TBI.
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Journal of neurotrauma · Apr 2009
Comparative StudyStrain differences in response to traumatic brain injury in Long-Evans compared to Sprague-Dawley rats.
The selected strain of rodent used in experimental models of traumatic brain injury is typically dependent upon the experimental questions asked and the familiarity of the investigator with a specific rodent strain. This archival study compares the injury responsiveness and recovery profiles of two popular outbred strains, the Long-Evans (LE) and the Sprague-Dawley (SD), after brain injury induced by lateral fluid percussion injury (LFPI). ⋯ Cortical volume loss was not significantly different, but close inspection of the data suggests the possibility that LE rats may be more susceptible to damage in the hemisphere contralateral to the injury site than are SD rats. It is hoped that the information provided here encourages greater attention to the subtle differences and similarities between strains in future pre-clinical efficacy studies of traumatic brain injury.
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Journal of neurotrauma · Apr 2009
alphaII-Spectrin breakdown product cerebrospinal fluid exposure metrics suggest differences in cellular injury mechanisms after severe traumatic brain injury.
Traumatic brain injury (TBI) produces alphaII-spectrin breakdown products (SBDPs) that are potential biomarkers for TBI. To further understand these biomarkers, the present study examined (1) the exposure and kinetic characteristics of SBDPs in cerebrospinal fluid (CSF) of adults with severe TBI, and (2) the relationship between these exposure and kinetic metrics and severity of injury. This clinical database study analyzed CSF concentrations of 150-, 145-, and 120-kDa SBDPs in 38 severe TBI patients. ⋯ A positive correlation was found between patients with longer elevations in intracranial pressure (ICP) measurements of 25mmHg or higher and those with a greater AUC and MRT for all three biomarkers. This is the first study to show that the biomarkers of proteolysis differentially associated with calpain and caspase-3 activity have distinct CSF exposure profiles following TBI that suggest a prominent role for calpain activity. Further studies are being conducted to determine if exposure and kinetic metrics for biofluid-based biomarkers can predict clinical outcome.