Experimental neurology
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Experimental neurology · Sep 2013
ReviewOpioid administration following spinal cord injury: implications for pain and locomotor recovery.
Approximately one-third of people with a spinal cord injury (SCI) will experience persistent neuropathic pain following injury. This pain negatively affects quality of life and is difficult to treat. Opioids are among the most effective drug treatments, and are commonly prescribed, but experimental evidence suggests that opioid treatment in the acute phase of injury can attenuate recovery of locomotor function. ⋯ A review of the literature, described here, suggests that caution is warranted when administering opioids after SCI. Opioid administration may synergistically contribute to the pathology of SCI to increase the development of pain, decrease locomotor recovery, and leave individuals at risk for infection. Considering these negative implications, it is important that guidelines are established for the use of opioids following spinal cord and other central nervous system injuries.
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Over the past 70years, diffuse axonal injury (DAI) has emerged as one of the most common and important pathological features of traumatic brain injury (TBI). Axons in the white matter appear to be especially vulnerable to injury due to the mechanical loading of the brain during TBI. As such, DAI has been found in all severities of TBI and may represent a key pathologic substrate of mild TBI (concussion). ⋯ In addition, recent evidence suggests that TBI may induce long-term neurodegenerative processes, such as insidiously progressive axonal pathology. Indeed, axonal degeneration has been found to continue even years after injury in humans, and appears to play a role in the development of Alzheimer's disease-like pathological changes. Here we review the current understanding of DAI as a uniquely mechanical injury, its histopathological identification, and its acute and chronic pathogenesis following TBI.
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Experimental neurology · Jul 2013
ReviewAdaptive deep brain stimulation (aDBS) controlled by local field potential oscillations.
Despite their proven efficacy in treating neurological disorders, especially Parkinson's disease, deep brain stimulation (DBS) systems could be further optimized to maximize treatment benefits. In particular, because current open-loop DBS strategies based on fixed stimulation settings leave the typical parkinsonian motor fluctuations and rapid symptom variations partly uncontrolled, research has for several years focused on developing novel "closed-loop" or "adaptive" DBS (aDBS) systems. aDBS consists of a simple closed-loop model designed to measure and analyze a control variable reflecting the patient's clinical condition to elaborate new stimulation settings and send them to an "intelligent" implanted stimulator. The major problem in developing an aDBS system is choosing the ideal control variable for feedback. Here we review current evidence on the advantages of neurosignal-controlled aDBS that uses local field potentials (LFPs) as a control variable, and describe the technology already available to create new aDBS systems, and the potential benefits of aDBS for patients with Parkinson's disease.
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There is increased interest in neurostimulation as a treatment for drug-resistant epilepsy. Two large pivotal trials have recently been completed, one using bilateral anterior thalamic stimulation and another employing closed loop responsive therapy of the brain. These are potential additions to the therapeutic options for neurostimulation in addition to already approved vagus nerve stimulation. This review will address the principles of the various types of neurostimulation, the results of the pivotal trials and the important considerations for interpreting the results of these trials which differ from trials of antiepileptic drugs.
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Experimental neurology · May 2013
ReviewCircadian dysfunction may be a key component of the non-motor symptoms of Parkinson's disease: insights from a transgenic mouse model.
Sleep disorders are nearly ubiquitous among patients with Parkinson's disease (PD), and they manifest early in the disease process. While there are a number of possible mechanisms underlying these sleep disturbances, a primary dysfunction of the circadian system should be considered as a contributing factor. Our laboratory's behavioral phenotyping of a well-validated transgenic mouse model of PD reveals that the electrical activity of neurons within the master pacemaker of the circadian system, the suprachiasmatic nuclei (SCN), is already disrupted at the onset of motor symptoms, although the core features of the intrinsic molecular oscillations in the SCN remain functional. ⋯ This raises the possibility that the sleep and circadian dysfunction experienced by PD patients may not merely be a subsidiary of the motor symptoms, but an integral part of the disease. Furthermore, we speculate that circadian dysfunction can even accelerate the pathology underlying PD. If these hypotheses are correct, more aggressive treatment of the circadian misalignment and sleep disruptions in PD patients early in the pathogenesis of the disease may be powerful positive modulators of disease progression and patient quality of life.