Neuroscience research
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Neuroscience research · May 2007
FK506 reduces the severity of cutaneous hypersensitivity in rats with a spinal cord contusion.
Spinal cord injury (SCI) leads to persistent pain as well as motor dysfunction, both of which lack effective therapeutics. The immunosuppressant FK506 (tacrolimus) has been shown to improve behavioral outcome following SCI in rats. Just prior to a mid-thoracic spinal cord contusion injury, rats were injected with either vehicle or FK506 and treatment was continued through the duration of the experiment. ⋯ Neither treated groups demonstrated an improvement in locomotor function. Thus, some SCI-induced pain is mediated by an FK506-sensitive mechanism. The data also suggest that motor and sensory dysfunctions resulting from SCI are mediated by distinct mechanisms, requiring the use of multiple therapeutic interventions.
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Neuroscience research · May 2007
Proteasomal inhibition in intracerebral hemorrhage: neuroprotective and anti-inflammatory effects of bortezomib.
Inflammation is an important pathophysiologic mechanism of injury induced by intracerebral hemorrhage (ICH). The ubiquitin-proteasome system (UPS) regulates the inflammatory responses via the up-regulation of several pro-inflammatory molecules. In this study, we determined that a potent proteasome inhibitor, bortezomib, exerted therapeutic effects in experimental model of ICH. ⋯ Bortezomib induced significant decrements of mRNA expression of TNF-alpha and IL-6. The production of iNOS and COX2 was also reduced significantly by bortezomib. We concluded that the early treatment with bortezomib induced a reduction in the early hematoma growth and mitigated the development of brain edema, coupled with a marked inhibitory effect on inflammation in ICH.
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Neuroscience research · Mar 2007
Therapeutic time window of post-ischemic mild hypothermia and the gene expression associated with the neuroprotection in rat focal cerebral ischemia.
Hypothermia is the only neuroprotective therapy proven to be clinically effective. Identifying the molecules that play important roles in the efficacy of hypothermia, we developed a multi-channel computer-controlled system, in which the brain temperatures of freely moving rats were telemetrically monitored and maintained below 35 degrees C, and examined the time window necessary to exert its significant neuroprotective effects. ⋯ On the basis of the window, comprehensive gene expression analyses using oligonucleotide microarrays were conducted and identified potential genes related to the efficacy of hypothermia, which included inflammatory genes like osteopontin, early growth response-1, or macrophage inflammatory protein-3alpha. Therefore, the neuroprotective effects of post-ischemic mild hypothermia were strongly suggested to be mainly associated with the reduction of neuronal inflammation.
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Neuroscience research · Jan 2007
Modulatory effects and afferent pathways of gastric electrical stimulation on rat thoracic spinal neurons receiving input from the stomach.
Gastric electrical stimulation (GES) has been suggested as a potential therapy for patients with obesity or gastric motility disorders. The aim of this study was to investigate the spinal mechanism of GES effects on gastric functions. Extracellular potentials of single spinal (T9-T10) neurons were recorded in pentobarbital anesthetized, paralyzed, ventilated male rats (n=19). ⋯ Resiniferatoxin (2.0microg/kg, i.v.), an ultrapotent agonist of vanilloid receptor-1, abolished excitatory responses to GD and GES in 4/4 neurons recorded in vagotomized rats. The results suggested that GES mainly had an excitatory effect on T9-T10 spinal neurons with gastric inputs; neuronal responses to GES were strengthened with stimulation at an increased pulse width and/or number of pulses. The modulatory effect of GES involved thoracic spinal (sympathetic) afferent fibers containing vanilloid receptor-1.
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Neuroscience research · Jan 2007
Synaptic plasticity modulates the spontaneous recovery of locomotion after spinal cord hemisection.
Several evidences have demonstrated that adult mammals could achieve a wide range of spontaneous sensory-motor recovery after spinal cord injury by means of various forms of neuroplasticity. In this study we evaluated the possibility that after low-thoracic spinal cord hemisection in the adult rat, significant hindlimb locomotor recovery could occur, and that this recovery may be driven, at least in part, by mechanisms of synaptic plasticity. ⋯ Conversely, neither the expression levels of synapsin-I nor the locomotor recovery were associated with the expression of brain-derived neurotrophic factor. Overall results indicate that after spinal cord hemisection, substantial recovery of hindlimb locomotion could occur spontaneously, and that synaptic plasticity within spinal circuitries below the level of the lesion, could be an important mechanism involved in these processes.