Adverse Consequences of Light at Night for Cerebral Ischemia

夜间光对脑缺血的不良后果

• 批准号: 9272450
• 负责人: Anne Courtney DeVries
• 金额: $ 39.58万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9272450
• 关键词: Acute; Address; Adoption; American Medical Association; Anxiety; Autonomic Dysfunction; Basic Science; Behavioral; Biological Markers; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cell Death; Cerebral Ischemia; Chronic; Chronic Disease; Circadian Rhythms; Clinical; Clinical Research; Clinical Sciences; Cognitive deficits; Cytokine Gene; Darkness; Data; Data Science; Disease; Environment; Epidemiology; Exposure to; Gene Expression; Goals; Goggles; Health; Heart; Heart Arrest; Hippocampus (Brain); Hospitals; Human; IL6 gene; Impairment; Individual; Industrialization; Inflammation; Inflammatory; Inflammatory Response; Interleukin-1 beta; Ischemia; Knowledge; Length; Life Style; Light; Lighting; Link; Malignant Neoplasms; Mediating; Medical; Mental Depression; Metabolic Diseases; Modernization; Modification; Mood Disorders; Morbidity - disease rate; Mus; Nervous System Trauma; Neuraxis; Neurocognitive; Neurons; Outcome; Patients; Peripheral; Physiological; Policies; Predisposition; Process; Property; Recovery; Reperfusion Therapy; Research Proposals; Resuscitation; Retina; Risk; System; TNF gene; Technology; Time; adverse outcome; behavioral impairment; cost; cytokine; design; epidemiologic data; excitotoxicity; experience; improved; indexing; light effects; mortality; mouse model; neuroinflammation; premature; prevent; public health relevance; reproductive; response

 DESCRIPTION (provided by applicant): Around the clock exposure to light has long been considered an innocuous consequence of industrialization and modernization. To the contrary, there is now accumulating epidemiological and experimental data suggesting that exposure to light at night can cause circadian disruption, which in turn increases an individual's susceptibiliy to a wide range of medical conditions from mood disorders to cancer. We propose that exposure to light at night, as often experienced in a hospital setting; also can hamper recovery following a cardiovascular incident. Much of the permanent damage that occurs to the central nervous system after cerebral ischemia is mediated by endogenous secondary processes, including inflammation and excitotoxicity. The overarching hypothesis of this proposal is that post-reperfusion light exposure at night compromises recovery from cerebral ischemia through modification of the early pathophysiological responses. In a mouse model of cardiac arrest (CA), exposure to dim light at night (dLAN) following cerebral ischemia increases neuronal damage and mortality compared to mice maintained in a standard light dark cycle (LD) after CA. Furthermore, proinflammatory cytokine gene expression is elevated 24 h following CA and a single night of dLAN, suggesting that inflammatory responses may underlie light-induced differences in ischemic outcome. These preliminary data suggest that environmental lighting has the potential to alter medical outcomes. A mouse model will be used to delineate the physiological mechanisms through which light at night increases neurological damage and mortality rate after cardiac arrest, and to determine whether certain wavelengths of lights are particularly detrimental. Taken together, the goals of the proposed studies are (1) to characterize the effects of light at night on experimental global ischemia outcome, (2) to establish whether there is a relationship between the increase in neuroinflammation among mice exposed to dLAN after CA and the observed increase in neuronal damage, behavioral impairments, and cardiac autonomic dysregulation, and (3) to determine whether the detrimental effects of dLAN on ischemic outcome can be prevented by using a limited range of light wavelengths at night. If only certain wave lengths of light alter ischemic outcomes, then relative simple technologies could be implemented to improve the recovery of patients with cardiovascular disease.

 描述（由应用程序提供）：长期以来，全天候暴露在光线下被认为是工业化和现代化的无害后果。相比之下，现在存在累积的流行病学和实验数据，表明夜间暴露在夜间可能会导致昼夜节律破坏，从而将个人的敏感性增加到从情绪障碍到癌症的广泛医疗状况。我们建议晚上暴露在医院环境中经历的照明。心血管事件后，还可能会阻碍恢复。脑缺血后，中枢神经系统发生的许多永久损害是由内源性次级过程（包括感染和兴奋性毒性）介导的。该提议的总体假设是，夜间重新灌注后的光线暴露会通过修改早期的病理生理反应来损害从脑缺血的恢复。与在标准的轻度黑暗周期（LD）中保持的小鼠相比，脑缺血后夜间暴露于夜间（DLAN）的小鼠模型，夜间暴露于昏暗的光（DLAN）。此外，CA和单个DLAN之后24小时促炎细胞因子基因表达升高，这表明炎症反应可能是缺血预后差异的光引起的差异。这些初步数据表明，环境照明有可能改变医疗结果。小鼠模型将用于描述物理机制，通过这些机制，夜间光在心脏骤停后会增加神经系统损害和死亡率，并确定某些灯光是否特别有害。同时，拟议的研究的目标是（1）表征晚上光对实验性全球缺血结果的影响（2），（2）确定在CA暴露于DLAN的小鼠中神经炎症的增加与观察到的神经元损害的增加，行为损害的增加，以及（3）对（3）的造成的效果以及（3）是否有疾病的效果，以及（3）。通过在夜间使用有限的光波长来预防。如果只有一定的波长度改变缺血结果，则可以实施相对简单的技术来改善心血管疾病患者的恢复。