Movement disorders : official journal of the Movement Disorder Society, Jan 4, 2015
In Parkinson's disease (PD), partial neuronal loss occurs in several arousal-promoting struct... more In Parkinson's disease (PD), partial neuronal loss occurs in several arousal-promoting structures, but the effects on arousability have not yet been studied. Polysomnographic analysis of 70 PD patients and 70 control subjects matched for age, sex, body mass index, apnea-hypopnea index (AHI), and periodic limb movements in sleep index (PLMSI). In PD patients, arousal frequency was diminished by 50% compared with controls (9.1 ± 7.6 vs. 18.6 ± 22.9/h; P < 0.001), and the correlations with AHI (rho = 0.266 vs. 0.503, P = 0.004) and PLMSI (rho = 0.082 vs. 0.354, P = 0.006) were weaker. Hoehn & Yahr stage was an independent negative predictor of arousal index (β = -0.297, P = 0.015). Normalization of heart rate increase after cortical arousals was prolonged in PD patients compared with controls (P = 0.003). Our findings indicate that the neurodegenerative process in PD is associated with an attenuated arousability to respiratory and motor events, and with an alteration of the hear...
Post-traumatic sleep-wake disturbances are common after acute traumatic brain injury. Increased s... more Post-traumatic sleep-wake disturbances are common after acute traumatic brain injury. Increased sleep need per 24 h and excessive daytime sleepiness are among the most prevalent post-traumatic sleep disorders and impair quality of life of trauma patients. Nevertheless, the relation between traumatic brain injury and sleep outcome, but also the link between post-traumatic sleep problems and clinical measures in the acute phase after traumatic brain injury has so far not been addressed in a controlled and prospective approach. We therefore performed a prospective controlled clinical study to examine (i) sleep-wake outcome after traumatic brain injury; and (ii) to screen for clinical and laboratory predictors of poor sleep-wake outcome after acute traumatic brain injury. Forty-two of 60 included patients with first-ever traumatic brain injury were available for follow-up examinations. Six months after trauma, the average sleep need per 24 h as assessed by actigraphy was markedly increa...
Natural killer (NK) cells participate in the immune response against solid organ allo- and xenogr... more Natural killer (NK) cells participate in the immune response against solid organ allo- and xenografts and are tightly regulated through signals mediated by inhibiting and activating receptors expressed on their cell surface. Human NK cytotoxicity against porcine endothelial cells (pEC) is mediated by the interaction of the activating human NK receptor hNKG2D and its corresponding ligand on pEC, porcine UL-16 binding protein 1 (pULBP1). The aim of the present study was to characterize the regulation of pULBP1 cell-surface expression on primary porcine aortic endothelial cells (PAEC). A monoclonal antibody (mAb; aE5-63) directed against pULBP1 was generated by immunizing C57BL/6 mice with the pEC line PEDSV.15, and used in cellular ELISA to determine pULBP1 cell surface expression. PAEC were either left untreated or stimulated with human or porcine cytokines [interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha)], human serum, cultured under hypoxic conditions, or infected with human or porcine cytomegalovirus (CMV). Neither human nor porcine IFN-gamma stimulation changed pULBP1 expression, whereas both human and porcine TNF-alpha stimulation as well as human and porcine CMV infection significantly decreased pULBP1 expression on PAEC. Coculture of PAEC with human serum strongly increased pULBP1 expression depending on the binding of human anti-pig antibodies. Exposure of PAEC to hypoxia only slightly increased pULBP1 expression. In conclusion, (i) the novel anti-pULBP1 IgM mAb aE5-63 represents a useful tool to study pULBP1/hNKG2D-mediated responses in xenotransplantation, and (ii) the expression of pULBP1, a human-pig cross-species functional hNKG2D ligand, on the surface of PAEC is modulated by various stimuli associated with transplantation.
Pain is a frequently observed non-motor symptom of patients with Parkinson&amp;amp;amp;amp;am... more Pain is a frequently observed non-motor symptom of patients with Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. In some patients, Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;#39;s-related pain responds to dopaminergic treatment. In the present study, we aimed to elucidate whether subthalamic deep brain stimulation has a similar beneficial effect on pain in Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease, and whether this effect can be predicted by a pre-operative l-dopa challenge test assessing pain severity. We prospectively analyzed 14 consecutive Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;#39;s patients with severe pain who underwent subthalamic deep brain stimulation. In 8 of these patients, pain severity decreased markedly with high doses of l-dopa, irrespective of the type and localization of the pain symptoms. In these patients, subthalamic deep brain stimulation provided an even higher reduction of pain severity than did dopaminergic treatment, and the majority of this group was pain-free after surgery. This effect lasted for up to 41 months. In the remaining 6 patients, pain was not improved by dopaminergic treatment nor by deep brain stimulation. Thus, we conclude that pain relief following subthalamic deep brain stimulation is superior to that following dopaminergic treatment, and that the response of pain symptoms to deep brain stimulation can be predicted by l-dopa challenge tests assessing pain severity. This diagnostic procedure could contribute to the decision on whether or not a Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;#39;s patient with severe pain should undergo deep brain stimulation for potential pain relief.
We have previously shown in a rat model of focal cerebral ischemia that sleep deprivation after s... more We have previously shown in a rat model of focal cerebral ischemia that sleep deprivation after stroke onset aggravates brain damage. Others reported that sleep deprivation prior to stroke is neuroprotective. The main aim of this study was to test the hypothesis that the neuroprotection may be related to an increase in sleep (sleep rebound) during the acute phase of stroke. Male Sprague Dawley rats (n=36) were subjected to continuous polygraphic recordings for baseline, total sleep deprivation (TSD), and 24h after ischemia. TSD for 6h was performed by gentle handling and immediately followed by ischemia. Focal cerebral ischemia was induced by permanent occlusion of distal branches of the middle cerebral artery. Control experiments included ischemia without SD (nSD) and sham surgery with TSD (n=6/group). Shortly after stroke, the amount of slow wave sleep (SWS) and paradoxical sleep (PS) increased significantly (p&amp;amp;lt;0.05) in the TSD/ischemia, resulting in an increase in the total sleep time by 30% compared to baseline, or by 20% compared with the nSD/ischemia group. The infarct volume decreased significantly by 50% in the TSD/ischemia compared to nSD group (p&amp;amp;lt;0.02). Removal of sleep rebound by allowing TSD-rats sleep for 24h before ischemia eliminated the reduction in the infarct size. Sleep deprivation results in sleep rebound and reduces brain damage. Sleep rebound may be causally related to the neuroprotection.
Movement disorders : official journal of the Movement Disorder Society, Jan 4, 2015
In Parkinson's disease (PD), partial neuronal loss occurs in several arousal-promoting struct... more In Parkinson's disease (PD), partial neuronal loss occurs in several arousal-promoting structures, but the effects on arousability have not yet been studied. Polysomnographic analysis of 70 PD patients and 70 control subjects matched for age, sex, body mass index, apnea-hypopnea index (AHI), and periodic limb movements in sleep index (PLMSI). In PD patients, arousal frequency was diminished by 50% compared with controls (9.1 ± 7.6 vs. 18.6 ± 22.9/h; P < 0.001), and the correlations with AHI (rho = 0.266 vs. 0.503, P = 0.004) and PLMSI (rho = 0.082 vs. 0.354, P = 0.006) were weaker. Hoehn & Yahr stage was an independent negative predictor of arousal index (β = -0.297, P = 0.015). Normalization of heart rate increase after cortical arousals was prolonged in PD patients compared with controls (P = 0.003). Our findings indicate that the neurodegenerative process in PD is associated with an attenuated arousability to respiratory and motor events, and with an alteration of the hear...
Post-traumatic sleep-wake disturbances are common after acute traumatic brain injury. Increased s... more Post-traumatic sleep-wake disturbances are common after acute traumatic brain injury. Increased sleep need per 24 h and excessive daytime sleepiness are among the most prevalent post-traumatic sleep disorders and impair quality of life of trauma patients. Nevertheless, the relation between traumatic brain injury and sleep outcome, but also the link between post-traumatic sleep problems and clinical measures in the acute phase after traumatic brain injury has so far not been addressed in a controlled and prospective approach. We therefore performed a prospective controlled clinical study to examine (i) sleep-wake outcome after traumatic brain injury; and (ii) to screen for clinical and laboratory predictors of poor sleep-wake outcome after acute traumatic brain injury. Forty-two of 60 included patients with first-ever traumatic brain injury were available for follow-up examinations. Six months after trauma, the average sleep need per 24 h as assessed by actigraphy was markedly increa...
Natural killer (NK) cells participate in the immune response against solid organ allo- and xenogr... more Natural killer (NK) cells participate in the immune response against solid organ allo- and xenografts and are tightly regulated through signals mediated by inhibiting and activating receptors expressed on their cell surface. Human NK cytotoxicity against porcine endothelial cells (pEC) is mediated by the interaction of the activating human NK receptor hNKG2D and its corresponding ligand on pEC, porcine UL-16 binding protein 1 (pULBP1). The aim of the present study was to characterize the regulation of pULBP1 cell-surface expression on primary porcine aortic endothelial cells (PAEC). A monoclonal antibody (mAb; aE5-63) directed against pULBP1 was generated by immunizing C57BL/6 mice with the pEC line PEDSV.15, and used in cellular ELISA to determine pULBP1 cell surface expression. PAEC were either left untreated or stimulated with human or porcine cytokines [interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha)], human serum, cultured under hypoxic conditions, or infected with human or porcine cytomegalovirus (CMV). Neither human nor porcine IFN-gamma stimulation changed pULBP1 expression, whereas both human and porcine TNF-alpha stimulation as well as human and porcine CMV infection significantly decreased pULBP1 expression on PAEC. Coculture of PAEC with human serum strongly increased pULBP1 expression depending on the binding of human anti-pig antibodies. Exposure of PAEC to hypoxia only slightly increased pULBP1 expression. In conclusion, (i) the novel anti-pULBP1 IgM mAb aE5-63 represents a useful tool to study pULBP1/hNKG2D-mediated responses in xenotransplantation, and (ii) the expression of pULBP1, a human-pig cross-species functional hNKG2D ligand, on the surface of PAEC is modulated by various stimuli associated with transplantation.
Pain is a frequently observed non-motor symptom of patients with Parkinson&amp;amp;amp;amp;am... more Pain is a frequently observed non-motor symptom of patients with Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. In some patients, Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;#39;s-related pain responds to dopaminergic treatment. In the present study, we aimed to elucidate whether subthalamic deep brain stimulation has a similar beneficial effect on pain in Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease, and whether this effect can be predicted by a pre-operative l-dopa challenge test assessing pain severity. We prospectively analyzed 14 consecutive Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;#39;s patients with severe pain who underwent subthalamic deep brain stimulation. In 8 of these patients, pain severity decreased markedly with high doses of l-dopa, irrespective of the type and localization of the pain symptoms. In these patients, subthalamic deep brain stimulation provided an even higher reduction of pain severity than did dopaminergic treatment, and the majority of this group was pain-free after surgery. This effect lasted for up to 41 months. In the remaining 6 patients, pain was not improved by dopaminergic treatment nor by deep brain stimulation. Thus, we conclude that pain relief following subthalamic deep brain stimulation is superior to that following dopaminergic treatment, and that the response of pain symptoms to deep brain stimulation can be predicted by l-dopa challenge tests assessing pain severity. This diagnostic procedure could contribute to the decision on whether or not a Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;#39;s patient with severe pain should undergo deep brain stimulation for potential pain relief.
We have previously shown in a rat model of focal cerebral ischemia that sleep deprivation after s... more We have previously shown in a rat model of focal cerebral ischemia that sleep deprivation after stroke onset aggravates brain damage. Others reported that sleep deprivation prior to stroke is neuroprotective. The main aim of this study was to test the hypothesis that the neuroprotection may be related to an increase in sleep (sleep rebound) during the acute phase of stroke. Male Sprague Dawley rats (n=36) were subjected to continuous polygraphic recordings for baseline, total sleep deprivation (TSD), and 24h after ischemia. TSD for 6h was performed by gentle handling and immediately followed by ischemia. Focal cerebral ischemia was induced by permanent occlusion of distal branches of the middle cerebral artery. Control experiments included ischemia without SD (nSD) and sham surgery with TSD (n=6/group). Shortly after stroke, the amount of slow wave sleep (SWS) and paradoxical sleep (PS) increased significantly (p&amp;amp;lt;0.05) in the TSD/ischemia, resulting in an increase in the total sleep time by 30% compared to baseline, or by 20% compared with the nSD/ischemia group. The infarct volume decreased significantly by 50% in the TSD/ischemia compared to nSD group (p&amp;amp;lt;0.02). Removal of sleep rebound by allowing TSD-rats sleep for 24h before ischemia eliminated the reduction in the infarct size. Sleep deprivation results in sleep rebound and reduces brain damage. Sleep rebound may be causally related to the neuroprotection.
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