Experimental neurology
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Many Parkinson's disease (PD) patients exhibit sleep disorders as part of their symptoms with evidence suggesting that REM sleep disorders may be intimately associated with this disease. Possible dysfunction in the circadian system in PD has received less attention, yet problems in circadian timing are common in neurodegenerative diseases. In the present study, we examined the expression of daily and circadian rhythms in the alpha-synuclein overexpressing (ASO) transgenic line. ⋯ In the ASO mice, the peak/trough expression of the clock gene PERIOD2 was normal in the master pacemaker of the circadian system: the suprachiasmatic nucleus (SCN); however, the daytime firing rate of SCN neurons was reduced in the mutant mice. Together, this data raises the possibility that a weakening of circadian output is a core feature of PD. The reduction in magnitude of circadian output would be expected to have functional consequences throughout the body.
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Experimental neurology · Oct 2011
Comparative StudyStructural and functional differences between neuropathy with and without pain?
We aimed to find functional and structural differences in neuropathy between patients with and without chronic pain following nerve injury. We included 30 patients requiring hand surgery after a trauma, with 21 reporting chronic pain for more than one year after the injury, while 9 did not suffer from injury-related chronic pain. We assessed mechanical sensitivity, thermal thresholds, electrically induced pain and axon reflex erythema and cutaneous nerve fiber density in skin biopsies of the injured site and its contralateral control. ⋯ Epidermal innervation density correlated best to warmth detection thresholds and deeper dermal innervation density to the area of the axon reflex erythema. No specific pattern of subjective, functional or structural parameters was detected that would separate the neuropathy patients into pain and non-pain patients. Specific staining of additional targets may help to improve our mechanistic understanding of pain development.
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Experimental neurology · Oct 2011
CD11d integrin blockade reduces the systemic inflammatory response syndrome after spinal cord injury.
Traumatic injury to the spinal cord triggers a systemic inflammatory response syndrome (SIRS), in which inflammatory cells from the circulation invade organs such as the liver, lung and kidney, leading to damage of these organs. Our previous study (Gris, et al, Exp. Neurol, 2008) demonstrated that spinal cord injury (SCI) activates circulating neutrophils that then invade the lung and kidney from 2 to 24 h after injury, increasing myeloperoxidase activity, cyclooxygenase-2 and matrix metalloproteinase-9 expression and lipid peroxidation in these organs. ⋯ The inflammatory responses within the lung and kidney were often greater after T4 than T12 injury. Clinical studies show that SIRS, with its associated organ failure, contributes significantly to the morbidity and mortality of SCI patients. This anti-integrin treatment may block the onset of SIRS after SCI.
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Experimental neurology · Sep 2011
Progesterone treatment normalizes the levels of cell proliferation and cell death in the dentate gyrus of the hippocampus after traumatic brain injury.
Traumatic brain injury (TBI) increases cell death in the hippocampus and impairs hippocampus-dependent cognition. The hippocampus is also the site of ongoing neurogenesis throughout the lifespan. Progesterone treatment improves behavioral recovery and reduces inflammation, apoptosis, lesion volume, and edema, when given after TBI. ⋯ The number of immature neurons that survived 5 days was increased following TBI, but progesterone treatment reduced this effect. Furthermore, TBI increased cell death and progesterone treatment reduced cell death to levels seen in intact rats. Together these findings suggest that progesterone treatment after TBI normalizes the levels of cell proliferation and cell death in the dentate gyrus of the hippocampus.
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Experimental neurology · Sep 2011
Deep brain stimulation of the subthalamic nucleus transiently enhances loss-chasing behaviour in patients with Parkinson's disease.
Dopaminergic treatments are associated with impulse control disorders such as pathological gambling in a subset of patients with Parkinson's Disease. While deep brain stimulation of the subthalamic nucleus has been reported to reduce symptoms of impulse control disorders in some Parkinson's Disease patients, little is known about its specific effects on gambling behaviour. In this experiment, we investigated the effects of deep brain stimulation of the subthalamic nucleus on one of the central features of pathological gambling: the tendency to chase losses. ⋯ These effects were not attributable to changes in state affect or to the motor impairments produced by the withdrawal of deep brain stimulation of the subthalamic nucleus. The effects of the stimulation on the value of losses chased were more pronounced in female than in male patients and reduced in patients taking dopamine receptor agonists. Collectively, these results suggest that deep brain stimulation of the subthalamic nucleus can transiently alter the evaluation of accumulated losses during gambling episodes in idiopathic Parkinson's Disease.