Journal of neurotrauma
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Journal of neurotrauma · Jul 2007
The fate of glucose during the period of decreased metabolism after fluid percussion injury: a 13C NMR study.
The present study determined the metabolic fate of [1, 2 13C2] glucose in male control rats and in rats with moderate lateral fluid percussion injured (FPI) at 3.5 h and 24 h post-surgery. After a 3-h infusion, the amount of 13C-labeled glucose increased bilaterally (26% in left/injured cerebral cortex and 45% in right cerebral cortex) at 3.5 h after FPI and in injured cortex (45%) at 24 h after injury, indicating an accumulation of unmetabolised glucose not seen in controls. No evidence of an increase in anaerobic glycolysis above control levels was found after FPI, as 13C-labeled lactate tended to decrease at both time points and was significantly reduced (33%) in the injured cortex at 24 h post-FPI. ⋯ The percentage of glucose metabolism through the pentose phosphate pathway (PPP) increased in the injured (13%) and contralateral (11%) cortex at 3.5 h post-FPI and in the injured cortex (9%) at 24 h post-injury. Based upon the changes in metabolite pools, our results show an injury-induced decrease in glucose utilization and oxidation within the first 24 h after FPI. Increased metabolism through the PPP would result in increased NADPH synthesis, suggesting a need for reducing equivalents after FPI to help restore the intracellular redox state and/or in response to free radical stress.
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Journal of neurotrauma · Jul 2007
COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury.
Traumatic brain injury (TBI) is a silent epidemic affecting approximately 1.4 million Americans annually, at an estimated annual cost of $60 billion in the United States alone. Despite an increased understanding of the pathophysiology of closed head injury, there remains no pharmacological intervention proven to improve functional outcomes in this setting. Currently, the existing standard of care for TBI consists primarily of supportive measures. ⋯ This was associated with a significant attenuation of microglial activation and neuronal death in the hippocampus, the neuroanatomical substrate for learning and memory. Rationally derived apoE mimetic peptides have been demonstrated to exert neuroprotective and anti-inflammatory effects in vitro and in clinically relevant models of brain injury. This represents a novel therapeutic strategy in the treatment of TBI.
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Journal of neurotrauma · Jul 2007
Decompressive craniectomy for traumatic brain injury: patient age and outcome.
The overall degree by which different patients may benefit from decompressive craniectomy (DC) remains controversial. In particular, the prognostic value of age has been investigated by very few studies. Many authors state there is no significant benefit in performing a DC in severe head injury after a certain age limit, with most placing the limit at 30-50 years of age. ⋯ Logistic regression analysis showed age as an independent predictive factor to outcome (p = 0.005). A difference in outcome exists among patients over 65 and patients aged
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Journal of neurotrauma · Jul 2007
The novel apolipoprotein E-based peptide COG1410 improves sensorimotor performance and reduces injury magnitude following cortical contusion injury.
It has previously been shown that small peptide molecules derived from the apolipoprotein E (ApoE) receptor binding region are anti-inflammatory in nature and can improve outcome following head injury. The present study evaluated the preclinical efficacy of COG1410, a small molecule ApoE-mimetic peptide (1410 daltons), following cortical contusion injury (CCI). Animals were prepared with a unilateral CCI of the sensorimotor cortex (SMC) or sham procedure. ⋯ The 0.8 mg/kg dose also reduced the number of glial fibrillary acid protein (GFAP+) reactive cells in the injured cortex. These results suggest that a single dose of COG1410 facilitates behavioral recovery and provides neuroprotection in a dose and task-dependent manner. Thus, the continued clinical development of ApoE based therapeutics is warranted and could represent a novel strategy for the treatment of traumatic brain injuries.
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Journal of neurotrauma · Jun 2007
Statistical image analysis of cerebral glucose metabolism in patients with cognitive impairment following diffuse traumatic brain injury.
The aim of this study was to explore the regional cerebral glucose metabolism (rCM) in patients with chronic stage traumatic brain injury (TBI) compared with normal controls. We also investigated the relationship between regional cerebral glucose metabolism and cognitive function. We performed 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) study using statistical parametric mapping (SPM) analysis in 36 diffuse axonal injury (DAI) patients (mean age +/- SD, 36.3 +/- 9.8 years). ⋯ DAI may induce functional disconnection and decreased neuronal activity, and finally lead to diffuse glucose hypometabolism. Low full-scale IQ scores may be related to significantly different underlying cognitive impairment. In supporting cognitive function following TBI, which showed diffuse cerebral metabolic reduction compared with normal controls, medial prefrontal cortex and anterior cingulate cortex may be an important component.