Adverse Consequences of Light at Night for Cerebral Ischemia

夜间光对脑缺血的不良后果

• 批准号: 9070024
• 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 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9070024
• 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 Research; Clinical Sciences; Cognitive deficits; Cytokine Gene; Data; Disease; Environment; Epidemiology; Exposure to; Gene Expression; Goals; Goggles; Health; Heart; Heart Arrest; Hippocampus (Brain); Hospitals; Human; IL6 gene; 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; excitotoxicity; experience; improved; indexing; light effects; mortality; mouse model; neuroinflammation; premature; prevent; 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（由申请人提供）：长期以来，全天候暴露在光线下一直被认为是工业化和现代化的无害后果。相反，现在越来越多的流行病学和实验数据表明，夜间暴露在光线下会导致昼夜节律紊乱，从而增加个体对从情绪障碍到癌症等多种疾病的易感性。我们建议夜间暴露在光线下，就像在医院环境中经常经历的那样；也可能妨碍心血管事件后的康复。脑缺血后中枢神经系统发生的大部分永久性损伤是由内源性次级过程介导的，包括炎症和兴奋性毒性。该提议的总体假设是，夜间再灌注后光照会通过改变早期病理生理反应而损害脑缺血的恢复。在心脏骤停 (CA) 小鼠模型中，与 CA 后维持标准光暗循环 (LD) 的小鼠相比，脑缺血后夜间暴露于昏暗光线 (dLAN) 会增加神经元损伤和死亡率。此外，促炎细胞因子基因表达在 CA 后 24 小时和 dLAN 的一个晚上升高，表明炎症反应可能是光诱导缺血结果差异的基础。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夜间光增加心脏骤停后神经损伤和死亡率的生理机制，并确定某些波长的光是否特别有害。总而言之，拟议研究的目标是（1）表征夜间光对实验性整体缺血结果的影响，（2）确定CA后暴露于dLAN的小鼠神经炎症的增加与观察到的神经元损伤、行为障碍和心脏自主神经失调的增加之间是否存在关系，以及（3）确定dLAN对缺血结果的有害影响是否可以 通过在夜间使用有限范围的光波长可以防止这种情况。如果只有特定波长的光会改变缺血结果，那么就可以采用相对简单的技术来改善心血管疾病患者的康复。