Journal of neurotrauma
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Journal of neurotrauma · Apr 2009
The effects of a ketogenic diet on behavioral outcome after controlled cortical impact injury in the juvenile and adult rat.
The ketogenic diet has been shown to have unique properties that make it a more suitable cerebral fuel under various neuropathological conditions (e.g., starvation, ischemia, and traumatic brain injury (TBI). Recently, age-dependent ketogenic neuroprotection was shown among postnatal day 35 (PND35) and PND45 rats after TBI, but not in PND17 and PND65 animals (Prins et al., 2005). The present study addresses the therapeutic potential of a ketogenic diet on motor and cognitive deficits after TBI. ⋯ During the same time period there was no significant difference between sham animals and CCI KG animals. The therapeutic effect of the ketogenic diet on beam walking and cognitive performance was not observed in PND75 animals. This finding supports our theory about age-dependent utilization and effectiveness of ketones as an alternative fuel after TBI.
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Journal of neurotrauma · Apr 2009
The long-term microvascular and behavioral consequences of experimental traumatic brain injury after hypothermic intervention.
Traumatic brain injury (TBI) has been demonstrated to induce cerebral vascular dysfunction that is reflected in altered responses to various vasodilators. While previous reports have focused primarily on the short-term vascular alterations, few have examined these vascular changes for more than 7 days, or have attempted to correlate these alterations with any persisting behavioral changes or potential therapeutic modulation. Accordingly, we evaluated the long-term microvascular and behavioral consequences of experimental TBI and their therapeutic modulation via hypothermia. ⋯ In contrast, data from the MWM task indicated that injured animals revealed persistent deficits in the spatial memory test performance, with hypothermia exerting no protective effects. Collectively, these data illustrate that TBI can evoke long-standing brain vascular and spatial memory dysfunction that manifest different responses to hypothermic intervention. These findings further illustrate the complexity of TBI and highlight the fact that the chosen hypothermic intervention may not necessarily exert a global protective response.
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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.
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Journal of neurotrauma · Apr 2009
Microdialysis of cytokines: methodological considerations, scanning electron microscopy, and determination of relative recovery.
Cerebral microdialysis is a monitoring technique with expanding clinical and research utility following traumatic brain injury. This study's aim was to determine the relative recovery for 12 cytokines using both crystalloid (CNS perfusion fluid) and colloid (CNS perfusion fluid supplemented with 3.5% human serum albumin) perfusate. Six CMA71 microdialysis catheters (nominal molecular weight cut-off 100 kDa) were perfused in vitro with either crystalloid or colloid and the relative recovery (%) determined for the cytokines as follows (crystalloid/colloid perfusate): IL-1alpha (50.6/48), IL-1beta (34.6/38.4), IL-1ra (21.9/38.4), IL-2 (17.1/52.8), IL-4 (26/56.7), IL-6 (9.8/25.5), IL-8 (47.7/73.4), IL-10 (2.9/8.7), IL-17 (14.4/43.7), TNF-alpha (4.4/31.2), MIP-1alpha (31.8/55.6), and MIP-1beta (31.9/50.1). ⋯ While colloid perfusate improves relative recovery, it causes a net influx of fluid into the microdialysis catheter, potentially dehydrating the extracellular space. This study is the first to systematically determine relative recovery in vitro for a wide range of cytokines. The two forms of perfusion fluid require direct comparison in vivo.
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Journal of neurotrauma · Apr 2009
Serial changes in the white matter diffusion tensor imaging metrics in moderate traumatic brain injury and correlation with neuro-cognitive function.
Diffuse axonal injury (DAI) that follows traumatic brain injury (TBI) is thought to be a major contributor to neurocognitive dysfunction that sometimes follows TBI. Conventional magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and neuropsychological tests (NPT) were performed on 38 TBI patients [hemorrhagic DAI (H-DAI, n=8), non-hemorrhagic (Nh-DAI, n=7), with no apparent DAI on conventional MRI (NA-DAI, n=23)] with a Glasgow Coma Scale score ranging between 9 and 13. The fractional anisotropy (FA) and mean diffusivity (MD) were quantified from different regions of the corpus callosum (CC), and peri-ventricular white matter (PWM) within 5-14 days and 6 months following TBI. ⋯ In patients without abnormalities on conventional MRI and DTI in the initial phase, a significant decrease in FA and increase in MD were observed in a few regions of the CC at 6 months, which was suggestive of demyelination/gliosis. The changes in FA and MD in the CC and PWM at 6 months follow-up showed significant correlation with some of the NPT performed in the three groups. DTI demonstrates axonopathy in the acute stage, as well as at secondary stages, at 6 months post-injury in the CC and PWM in regions of normal-appearing white matter on conventional MRI.