Adverse Consequences of Light at Night for Cerebral Ischemia

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 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.