Ischemic stroke destabilizes circadian rhythms.
Ischemic stroke destabilizes circadian rhythms.
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DOI：
10.1186/1740-3391-6-9
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发表时间：
2008-10-15
影响因子：
--
通讯作者：
Wang, Michael M
中科院分区：
文献类型：
--
作者：
Meng, He;Liu, Tiecheng;Wang, Michael M
背景技术背景：中枢昼夜节律起搏器是心血管、内分泌和神经生理学每日节律变化的非常强大的调节器。环境光照条件是昼夜节律的强大调节器，但疾病状态对昼夜节律的调节尚不清楚。在这里，我们研究的影响，缺血性中风的昼夜节律的大鼠使用高分辨率松果体microdialysis.METHODS：大鼠被关押在LD 12：12小时的条件和松果体微透析监测，以确定基线褪黑激素的时间配置文件。在证明褪黑激素的昼夜节律表达处于稳定状态后，使用大脑中动脉的两小时管腔内细丝闭塞对大鼠进行实验性中风。将动物放回笼中，重新开始褪黑激素监测。在中风之前和之后计算褪黑激素分泌的开始、偏移和持续时间的时间，以确定褪黑激素分泌的昼夜节律的变化。在监测期结束时，大脑进行了分析，以确定梗死volume.RESULTS：大鼠表现出立即转移褪黑激素的时间中风后。我们观察到了广泛的干扰褪黑激素的时间在随后的日子里，大鼠表现出发作/偏移模式，其中包括：提前/提前，提前/延迟，延迟/提前，延迟/延迟。褪黑激素节律显示中风后几天的长期不稳定性，与大多数大鼠表现出提前和延迟褪黑激素的发病和持续时间之间的日常交替。褪黑激素分泌的持续时间在中风时发生变化，这种变化强烈地取决于褪黑激素起效时间的变化。梗死面积和方向或幅度的褪黑激素phase shifting.CONCLUSION之间没有相关性：这是第一次证明，中风引起立即改变松果体褪黑激素分泌的时间，表明皮质和基底节梗死影响褪黑激素的节奏的时间。褪黑激素变化的异质性方向和幅度表明，下丘脑计时的上游调节可能是解剖学上的扩散和机械复杂。最后，我们的研究证实了使用松果体微透析来评估神经系统疾病对昼夜功能的影响。
BACKGROUND: The central circadian pacemaker is a remarkably robust regulator of daily rhythmic variations of cardiovascular, endocrine, and neural physiology. Environmental lighting conditions are powerful modulators of circadian rhythms, but regulation of circadian rhythms by disease states is less clear. Here, we examine the effect of ischemic stroke on circadian rhythms in rats using high-resolution pineal microdialysis.METHODS: Rats were housed in LD 12:12 h conditions and monitored by pineal microdialysis to determine baseline melatonin timing profiles. After demonstration that the circadian expression of melatonin was at steady state, rats were subjected to experimental stroke using two-hour intralumenal filament occlusion of the middle cerebral artery. The animals were returned to their cages, and melatonin monitoring was resumed. The timing of onset, offset, and duration of melatonin secretion were calculated before and after stroke to determine changes in circadian rhythms of melatonin secretion. At the end of the monitoring period, brains were analyzed to determine infarct volume.RESULTS: Rats demonstrated immediate shifts in melatonin timing after stroke. We observed a broad range of perturbations in melatonin timing in subsequent days, with rats exhibiting onset/offset patterns which included: advance/advance, advance/delay, delay/advance, and delay/delay. Melatonin rhythms displayed prolonged instability several days after stroke, with a majority of rats showing a day-to-day alternation between advance and delay in melatonin onset and duration. Duration of melatonin secretion changed in response to stroke, and this change was strongly determined by the shift in melatonin onset time. There was no correlation between infarct size and the direction or amplitude of melatonin phase shifting.CONCLUSION: This is the first demonstration that stroke induces immediate changes in the timing of pineal melatonin secretion, indicating that cortical and basal ganglia infarction impacts the timing of melatonin rhythms. The heterogeneous direction and amplitude of melatonin shifts suggests that the upstream regulation of hypothalamic timekeeping is likely anatomically diffuse and mechanistically complex. Finally, our study exemplifies the use of pineal microdialysis to evaluate the effect of neurological diseases on circadian function.