Journal of neurotrauma
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Journal of neurotrauma · Jul 2009
The effects of age and ketogenic diet on local cerebral metabolic rates of glucose after controlled cortical impact injury in rats.
Previous studies from our laboratory have shown the neuroprotective potential of ketones after TBI in the juvenile brain. It is our premise that acutely after TBI, glucose may not be the optimum fuel and decreasing metabolism of glucose in the presence of an alternative substrate will improve cellular metabolism and recovery. The current study addresses whether TBI will induce age-related differences in the cerebral metabolic rates for glucose (CMRglc) after cortical controlled impact (CCI) and whether ketone metabolism will further decrease CMRglc after injury. ⋯ The presence of ketones after injury further reduced CMRglc in PND35 and normalized CMRglc in PND70 rats at 7 days bilaterally after injury. The changes in CMRglc seen in PND35 TBI rats on the KG diet were associated with decreased contusion volume. These results suggest that conditions of reduced glucose utilization and increased alternative substrate metabolism may be preferable acutely after TBI in the younger rat.
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Journal of neurotrauma · Jul 2009
Reliability of cutaneous electrical perceptual threshold in the assessment of sensory perception in patients with spinal cord injury.
The electrical perceptual threshold (EPT) test complements the American Spinal Injury Association (ASIA) assessment of cutaneous sensory function by providing a quantitative assessment for each dermatome. The aim here was to establish the reliability of the EPT by examining inter- and intra-rater repeatability of test results in spinal cord injury (SCI). Twelve persons with incomplete spinal cord injury (iSCI; two stable at >20 months and 10 sub-acute at <9 months post-injury) and 12 control subjects took part. ⋯ There was a significant correlation (Pearson's r = 0.93) between EPTs for four different dermatomes of control subjects assessed using two different types of stimulator. EPT provides an objective and quantitative measure of threshold for cutaneous sensory function. The method has good inter- and intra-rater reliability, and can be assessed using different stimulators.
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Journal of neurotrauma · Jul 2009
Reduced vascular endothelial growth factor expression in contusive spinal cord injury.
Vascular endothelial growth factor (VEGF) is being investigated as a potential interventional therapy for spinal cord injury (SCI). In the current study, we examined SCI-induced changes in VEGF protein levels using Western blot analysis around the epicenter of injury. Our results indicate a significant decrease in the levels of VEGF(165) and other VEGF isoforms at the lesion epicenter 1 day after injury, which was maintained up to 1 month after injury. ⋯ However, exogenously administered VEGF(165) at the time of injury did not affect the number of sparred neurons. In contrast, exogenous administration of VEGF antibody that inhibits actions of not only VEGF(165) but also of several other VEGF isoforms, significantly decreased number of sparred neurons after SCI. Together these results indicate a general reduction of VEGF isoforms following SCI and that isoforms other than VEGF(165) (e.g., VEGF(121) and/or VEGF(189)) provide neuroprotection, suggesting that VEGF(165) isoform is likely involved in other pathophysiological process after SCI.
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Journal of neurotrauma · Jul 2009
Wnt-Ryk signaling mediates axon growth inhibition and limits functional recovery after spinal cord injury.
Wnt proteins are a large family of diffusible factors that play important roles in embryonic development, including axis patterning, cell fate specification, proliferation, and axon development. It was recently demonstrated that Ryk (receptor related to tyrosine kinase) is a conserved high-affinity Wnt receptor, and that Ryk-Wnt interactions guide corticospinal axons down the spinal cord during development. Here, we report that the Ryk-Wnt signal mediates the inhibition of corticospinal axon growth in the adult spinal cord. ⋯ In vitro, Wnt-5a inhibits the neurite growth of postnatal cerebellar neurons by activating RhoA/Rho-kinase. In rats with thoracic spinal cord contusion, intrathecal administration of a neutralizing antibody to Ryk resulted in significant axonal growth of the corticospinal tract and enhanced functional recovery. Thus, reexpression of the embryonic repulsive cues in adult tissues contributes to the failure of axon regeneration in the central nervous system.
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Journal of neurotrauma · Jul 2009
Repeated traumatic brain injury affects composite cognitive function in piglets.
Cumulative effects of repetitive mild head injury in the pediatric population are unknown. We have developed a cognitive composite dysfunction score that correlates white matter injury severity in neonatal piglets with neurobehavioral assessments of executive function, memory, learning, and problem solving. Anesthetized 3- to 5-day-old piglets were subjected to single (n = 7), double one day apart (n = 7), and double one week apart (n = 7) moderate (190 rad/s) rapid non-impact axial rotations of the head and compared to instrumented shams (n = 7). ⋯ In our immature large animal model of TBI, two head rotations produced poorer outcome as assessed by neuropathology and neurobehavioral functional outcomes compared to that with single rotations. More importantly, we have observed an increase in injury severity and mortality when the head rotations occur 24 h apart compared to 7 days apart. These observations have important clinical translation to infants subjected to repeated inflicted head trauma.