Experimental neurology
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Experimental neurology · May 2012
Altered ventral striatal activation during reward and punishment processing in premanifest Huntington's disease: a functional magnetic resonance study.
Recent research using various neuroimaging methods revealed the crucial role of the striatum concerning the neuropathology of Huntington's disease. Degenerative changes located in the basal ganglia are already observable in premanifest stages of Huntington's disease (pre-HD), i.e., before the onset of manifest motor symptoms. Although the impact of the striatum on reward and punishment processing is well-established in healthy subjects, these processes have not been investigated in manifest and premanifest HD subjects using functional magnetic resonance imaging (fMRI) so far. ⋯ In contrast to pre-HD(far) and healthy subjects, no significant ventral striatal discrimination between punishing and control cues was detected in pre-HD(near) subjects. In the present study, we demonstrated for the first time significant differences in valence discrimination in pre-HD(near) subjects compared to pre-HD(far) subjects and healthy controls. Altered reward and punishment processing could therefore reflect a motivational deficit that may contribute to the pathogenesis of Huntington's disease.
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Experimental neurology · May 2012
Comprehensive locomotor outcomes correlate to hyperacute diffusion tensor measures after spinal cord injury in the adult rat.
In adult rats, locomotor deficits following a contusive thoracic spinal cord injury (SCI) are caused primarily by white matter loss/dysfunction at the epicenter. This loss/dysfunction decreases descending input from the brain and cervical spinal cord, and decreases ascending signals in long propriospinal, spinocerebellar and somatosensory pathways, among many others. Predicting the long-term functional consequences of a contusive injury acutely, without knowledge of the injury severity is difficult due to the temporary flaccid paralysis and loss of reflexes that accompany spinal shock. ⋯ In the adult rat model of SCI, we found that hyperacute (<3h post-injury) DTI of the lateral and ventral white matter at the injury epicenter was predictive of both electrophysiological and behavioral (locomotor) recovery at 4 weeks post-injury, despite the presence of flaccid paralysis/spinal shock. Regions of white matter with a minimum axial diffusivity of 1.5 μm(2)/ms at 3h were able to conduct action potentials at 4 weeks, and axial diffusivity within the lateral funiculus was highly predictive of locomotor function at 4 weeks. These observations suggest that acute DTI should be useful to provide functional predictions for spared white matter following contusive spinal cord injuries clinically.
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Experimental neurology · May 2012
P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin-induced neuropathy.
Patients suffering from sensory neuropathy due to skin denervation frequently have paradoxical manifestations of reduced nociception and neuropathic pain. However, there is a lack of satisfactory animal models to investigate these phenomena and underlying mechanisms. We developed a mouse system of neuropathy induced by resiniferatoxin (RTX), a capsaicin analog, and examined the functional significance of P2X3 receptor in neuropathic pain. ⋯ The number of P2X3(+)/ATF3(+) neurons was linearly correlated with mechanical thresholds (p=0.0017). The peripheral expression of P2X3 receptor in dermal nerves was accordingly increased (p=0.016), and an intraplantar injection of the P2X3 antagonists, A-317491 and TNP-ATP, relieved mechanical allodynia in a dose-dependent manner. In conclusion, RTX-induced sensory neuropathy with upregulation of P2X3 receptor for peripheral sensitization of mechanical allodynia, which provides a new therapeutic target for neuropathic pain after skin denervation.
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Experimental neurology · May 2012
ReviewMyelin associated inhibitors: a link between injury-induced and experience-dependent plasticity.
In the adult, both neurologic recovery and anatomical growth after a CNS injury are limited. Two classes of growth inhibitors, myelin associated inhibitors (MAIs) and extracellular matrix associated inhibitors, limit both functional recovery and anatomical rearrangements in animal models of spinal cord injury. ⋯ Initially described as inhibitors of axonal regeneration, subsequent work has demonstrated that MAIs also limit activity and experience-dependent plasticity in the intact, adult CNS. MAIs therefore represent a point of convergence for plasticity that limits anatomical rearrangements regardless of the inciting stimulus, blurring the distinction between injury studies and more "basic" plasticity studies.
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Experimental neurology · May 2012
ReviewNeuronal plasticity after a human spinal cord injury: positive and negative effects.
In patients suffering an incomplete spinal cord injury (SCI) an improvement in walking function can be achieved by providing a functional training with an appropriate afferent input. In contrast, in immobilized incomplete and complete subjects a negative neuroplasticity leads to a neuronal dysfunction. After an SCI, neuronal centers below the level of lesion exhibit plasticity that either can be exploited by specific training paradigms or undergo a degradation of function due to the loss of appropriate input. ⋯ The exhaustion of locomotor activity is also observed in non-ambulatory patients with an incomplete SCI. It is assumed that in chronic SCI the patient's immobility results in a reduced input from supraspinal and peripheral sources and leads to a dominance of inhibitory drive within spinal neuronal circuitries underlying locomotor pattern and spinal reflex generation. A training with an enhancement of an appropriate proprioceptive input early after an SCI might serve as an intervention to prevent neuronal dysfunction.