Journal of neurotrauma
-
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.
-
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.