Experimental neurology
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Experimental neurology · Dec 2005
Comparative StudyReinnervation of hind limb extremity after lumbar dorsal root ganglion injury.
Loss of dorsal root ganglion neuron, or injury to dorsal roots, induces permanent somatosensory defect without therapeutic option. We explored an approach to restoring hind limb somatosensory innervation after elimination of L4, L5 and L6 dorsal root ganglion neurons in rats. Somatosensory pathways were reconstructed by connecting L4, L5 and L6 lumbar dorsal roots to T10, T11 and T12 intercostal nerves, respectively, thus allowing elongation of thoracic ganglion neuron peripheral axons into the sciatic nerve. ⋯ Hind limb retraction in response to nociceptive stimulation of the reinnervated footpads and reversion of skin lesions suggested partial recovery of sensory function. Proprioceptive defects persisted. Delayed somatosensory reinnervation of the hind limb after destruction of lumbar dorsal root neurons in rats indicates potential approaches to reduce chronic disability after severe injury to somatosensory pathways.
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Experimental neurology · Dec 2005
Comparative Study Clinical TrialRepetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex and cortical excitability in patients with major depressive disorder.
Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex is a relatively non-invasive technique with putative therapeutic effects in major depression. However, the exact neurophysiological basis of these effects needs further clarification. ⋯ These results suggest that repetitive transcranial magnetic stimulation of the dorsolateral, prefrontal cortex may have inhibitory effects on motor cortical neuronal excitability in patients with major depressive disorder. Furthermore, measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of antidepressant stimulation techniques like rTMS.
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Experimental neurology · Dec 2005
Comparative StudyFAS deficiency reduces apoptosis, spares axons and improves function after spinal cord injury.
After spinal cord injury (SCI), apoptosis of neurons and oligodendrocytes is associated with axonal degeneration and loss of neurological function. Recent data have suggested a potential role for FAS death receptor-mediated apoptosis in the pathophysiology of SCI. In this study, we examined the effect of FAS deficiency on SCI in vitro and in vivo. ⋯ FAS deficiency was also associated with improved locomotor recovery, axonal sparing and preservation of oligodendrocytes and myelin. However, FAS deficiency did not result in a significant increase in surviving neurons in the spinal cord at 6 weeks after injury, likely reflecting the importance of other cell death mechanisms for neurons. We conclude that inhibition of the FAS pathway may be a clinically attractive neuroprotective strategy directed towards oligodendroglial and axonal preservation in the treatment of SCI and neurotrauma.
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Experimental neurology · Nov 2005
Comparative StudyTissue displacement and impact force are important contributors to outcome after spinal cord contusion injury.
Spinal cord contusion injury in rodents is widely used as a model for spinal cord trauma in humans. Several biomechanical variables can influence injury outcome. ⋯ Our work indicates that there is a linear relationship between force and tissue displacement, and that both these factors contribute to injury outcome. Furthermore, our work also suggests that setting narrow limits for the actual force applied (+/-5 kdyn) and tissue displacement (within a 200 microm range) will yield more consistent outcomes and provide greater sensitivity in detecting changes, regardless of the type of impactor device used.
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Experimental neurology · Nov 2005
Effects of the perivascular space on convection-enhanced delivery of liposomes in primate putamen.
Convection-enhanced delivery has recently entered the clinic and represents a promising new therapeutic option in the field of neurodegenerative diseases and treatment of brain tumors. Understanding of the principles governing delivery and flow of macromolecules within the CNS is still poorly understood and requires more investigation of the microanatomy and fluid dynamics of the brain. Our previously established, reflux-free convection-enhanced delivery (CED) technique and real-time imaging MR method for monitoring CED delivery of liposomes in primate CNS allowed us to closely monitor infusions of putamen. ⋯ The results may explain side effects seen in current clinical trials using CED. In addition, they clearly show the necessity for a monitoring technique for future direct delivery of therapeutic agents to the human central nervous system. Based on these findings, we believe that the physiological concept that the perivascular space serves as a conduit for distribution of endogenous molecules within the CNS also applies to interstitially infused agents.