Adverse Consequences of Light at Night for Cerebral Ischemia

 描述(申请人提供)：长期以来，全天候暴露在阳光下一直被认为是工业化和现代化的无害后果。相反，现在有越来越多的流行病学和实验数据表明，夜间暴露在阳光下会导致昼夜节律紊乱，这反过来又增加了个人对从情绪障碍到癌症等各种疾病的易感性。我们认为，夜间暴露在光线下，就像在医院中经常经历的那样，也会阻碍心血管事件后的康复。脑缺血后中枢神经系统发生的永久性损伤大部分是由内源性次级过程介导的，包括炎症和兴奋性毒性。这一建议的主要假设是，再灌注后夜间光照暴露通过改变早期的病理生理反应，损害了脑缺血的恢复。在心脏骤停(CA)的小鼠模型中，与CA后维持在标准明暗周期(LD)的小鼠相比，脑缺血后暴露于夜间昏暗(DLan)会增加神经元损伤和死亡率。此外，促炎症细胞因子基因的表达在CA和dLan一夜后24小时升高，提示炎症反应可能是光诱导的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。一个小鼠模型将被用来描绘夜间光线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线是否特别有害。综上所述，拟议研究的目标是(1)表征夜间光照对实验性全脑缺血结局的影响，(2)确定CA后暴露于dLan的小鼠的神经炎症增加是否与观察到的神经元损伤、行为障碍和心脏自主神经调节障碍的增加之间存在关系，以及(3)确定是否可以通过在夜间使用有限范围的光波长来预防dLan对缺血结局的有害影响。如果只有特定波长的光改变缺血结果，那么可以实施相对简单的技术来改善心血管疾病患者的康复。

 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.