Dim light at night shifts microglia to a pro-inflammatory state after cerebral ischemia, altering stroke outcome in mice

Apr 27, 2024Experimental neurology

Dim nighttime light shifts brain immune cells toward inflammation after stroke, changing recovery in mice

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Abstract

A single night of dim light at night (5 lx) following a stroke increased infarct size and sensorimotor deficits in mice.

Dim light at night (dLAN) may disrupt immune responses and worsen stroke outcomes.
Mice exposed to dLAN showed increased infarct size and sensorimotor impairments after ischemic stroke.
Reduced survival rates were observed in male mice subjected to dLAN following stroke.
dLAN altered microglial behavior, increasing the presence of pro-inflammatory markers linked to poor recovery.
Microglial depletion using a specific inhibitor resulted in similar infarct sizes regardless of lighting conditions.
These findings suggest that environmental light exposure can fundamentally change immune cell behavior, potentially leading to increased neuronal death after stroke.

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Circadian rhythms are endogenous biological cycles that regulate physiology and behavior and are set to precisely 24-h by light exposure. Light at night (LAN) dysregulates physiology and function including immune response; a critical component that contributes to stroke pathophysiological progression of neuronal injury and may impair recovery from injury. The goal of this study is to explore the effects of dim LAN (dLAN) in a murine model of ischemic stroke to assess how nighttime lighting from hospital settings can affect stroke outcome. Further, this study sought to identify mechanisms underlying pathophysiological changes to immune response after circadian disruption. Male and female adult Swiss Webster (CFW) mice were subjected to transient or permanent focal cerebral ischemia, then were subsequently placed into either dark night conditions (LD) or one night of dLAN (5 lx). 24 h post-stroke, sensorimotor impairments and infarct sizes were quantified. A single night of dLAN following MCAO increased infarct size and sensorimotor deficits across both sexes and reduced survival in males after 24 h. Flow cytometry was performed to assess microglial phenotypes after MCAO, and revealed that dLAN altered the percentage of microglia that express pro-inflammatory markers (MHC II+ and IL-6) and microglia that express CD206 and IL-10 that likely contributed to poor ischemic outcomes. Following these results, microglia were reduced in the brain using Plexxikon 5622 (PLX 5622) a CSFR1 inhibitor, then the mice received an MCAO and were exposed to LD or dLAN conditions for 24 h. Microglial depletion by PLX5622 resulted in infarct sizes that were comparable between lighting conditions. This study provides supporting evidence that environmental lighting exacerbates ischemic injury and post-stroke mortality by a biological mechanism that exposure to dLAN causes a fundamental shift of activated microglial phenotypes from beneficial to detrimental at an early time point after stroke, resulting in irreversible neuronal death.

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Dim light at night shifts microglia to a pro-inflammatory state after cerebral ischemia, altering stroke outcome in mice

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