Journal of neurotrauma
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Journal of neurotrauma · Jul 2011
Short-term moderate hypocapnia augments detection of optimal cerebral perfusion pressure.
An autoregulation-oriented strategy has been proposed to guide neurocritical therapy toward the optimal cerebral perfusion pressure (CPPOPT). The influence of ventilation changes is, however, unclear. We sought to find out whether short-term moderate hypocapnia (HC) shifts the CPPOPT or affects its detection. ⋯ Moderate HC did not shift this CPPOPT but enabled its detection in another 17 patients (CPPOPT left: 83.94±14.82; right: 85.28±14.73 mm Hg). The detection of CPPOPT was achieved via significantly improved Mx-autoregulatory index and an increase of CPP mean. It appeared that short-term moderate HC augmented the detection of an optimum CPP, and may therefore usefully support CPP-guided therapy in patients with TBI.
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Journal of neurotrauma · Jul 2011
Comparative StudyObjective measures of motor dysfunction after compression spinal cord injury in adult rats: correlations with locomotor rating scores.
Precise assessment of motor deficits after traumatic spinal cord injury (SCI) in rodents is crucial for understanding the mechanisms of functional recovery and testing therapeutic approaches. Here we analyzed the applicability to a rat SCI model of an objective approach, the single-frame motion analysis, created and used for functional analysis in mice. Adult female Wistar rats were subjected to graded compression of the spinal cord. ⋯ FSA co-varied with RHI only in the severely impaired rats, while RHI and CLS were barely correlated. Our findings suggest that the numerical parameters estimate, as intended by design, predominantly different aspects of locomotion. The use of these objective measures combined with BBB rating provides a time- and cost-efficient opportunity for versatile and reliable functional evaluations in both severely and moderately impaired rats, combining clinical assessment with precise numerical measures.
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Journal of neurotrauma · Jul 2011
Attenuation of astrocyte activation by TAT-mediated delivery of a peptide JNK inhibitor.
Astrocyte activation contributes to the brain's response to disease and injury. Activated astrocytes generate harmful radicals that exacerbate brain damage including nitric oxide, peroxides and superoxides. Furthermore, reactive astrocytes hinder regeneration of damaged neural circuits by secreting neuro-developmental inhibitors and glycosaminoglycans (GAGs), which physically block growth cone extension. ⋯ TAT fused to a peptide JNK inhibitor delivered the peptide inhibitor to activated astrocytes and significantly reduced activation. Our study is the first to report significant and direct modulation of astrocyte activation with a peptide JNK inhibitor. Our promising in vitro results warrant in vivo follow-up, as TAT-mediated protein delivery may have broad therapeutic potential for preventing astrocyte activation with the possibility of limiting off-target, negative side effects.
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Journal of neurotrauma · Jul 2011
Post-stroke hypothermia provides neuroprotection through inhibition of AMP-activated protein kinase.
Hypothermia is robustly protective in pre-clinical models of both global and focal ischemia, as well as in patients after cardiac arrest. Although the mechanism for hypothermic neuroprotection remains unknown, reducing metabolic drive may play a role. Capitalizing on the beneficial effects of hypothermia while avoiding detrimental effects such as infection will be the key to moving this therapy forward as a treatment for stroke. ⋯ These effects were mediated by a reduction in AMPK activation rather than a reduction in LKB1, an upstream AMPK kinase. In summary, these studies provide evidence that hypothermia exerts its protective effect in part by inhibiting AMPK activation in experimental focal stroke. This suggests that AMPK represents a potentially important biological target for stroke treatment.
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Journal of neurotrauma · Jul 2011
Selective brain cooling in rats ameliorates intracerebral hemorrhage and edema caused by penetrating brain injury: possible involvement of heme oxygenase-1 expression.
Brain edema formation associated with trauma-induced intracerebral hemorrhage (ICH) is a clinical complication with high mortality. Studies have shown that heme oxygenase-1 (HO-1) plays an important role in ICH-induced brain edema. In order to understand the role of HO-1 in the protective effect of selective brain cooling (SBC), we investigated the time course of HO-1 changes following penetrating ballistic-like brain injury (PBBI) in rats. ⋯ SBC significantly decreased PBBI-induced heme concentration, attenuated HO-1 upregulation, and concomitantly reduced brain water content. These results suggest that the neuroprotective effects of SBC may be partially mediated by reducing the heme accumulation, which reduced injury-mediated upregulation of HO-1, and in turn ameliorated edema formation. Collectively, these results suggest a potential value of HO-1 as a diagnostic and/or therapeutic biomarker in hemorrhagic brain injury.