Spinal Cord Injury in Rats Disrupts the Circadian System

Gaudet, Andrew D.; Ayala, Monica T.; Schleicher, Wolfgang E.; Smith, Elana J.; D’Angelo, Heather; Maier, Steven F.; Watkins, Linda R.

doi:10.1523/eneuro.0328-18.2018

Cited by 34 publications

(24 citation statements)

References 74 publications

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“…These data are excluded from the figures and analysis for clarity as described in. 22 Fever indices were calculated as the sum of the change per hour from individual baselines and assessed using Student's unpaired t tests for the 0-3 and 3-9 hours after DT. For the CLAMS data, we show diurnal wave patterns from immediately after entering the CLAMS to 56 hours later, however, we statistically analyzed only the first active period (12 hours) as data from 24 to 48 hours after entering the CLAMS (32 to 56 hours after the first exposure to DT) have already been reported for these animals.…”

Section: Discussionmentioning

confidence: 99%

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Microglial ablation in rats disrupts the circadian system

et al. 2020

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Research is increasingly revealing new roles for microglia in the developed brain beyond their well-known function in protecting it from pathogens and injury. 1,2 For example, recent work has demonstrated microglia are likely to be important for memory processing and executive function. [3][4][5][6] Microglial activity directed at pruning of synapses mediates memory degradation in a complement-dependent manner in a contextual fear conditioning task. 3 Likewise, spatial learning is impaired in animals that are unable to reduce their CA1 microglial density during task acquisition 7 and recognition memory is improved when microglia repopulate the brain after depletion. 8 Roles for microglia have also emerged for regulation of feeding and satiety, 9 and in modifying pain responses. 10,11

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Section: Discussionmentioning

confidence: 99%

“…Here, we investigate diurnal rhythms subject to standard 12 hour light cues, true circadian rhythms being endogenous rhythms occurring even in the absence of such cues. 22 2 | MATERIALS AND METHODS…”

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confidence: 99%

Microglial ablation in rats disrupts the circadian system

et al. 2020

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“…In contrast, the potential health consequences of acute exposure to light at night remain underexplored. Patients recovering in hospitals may be particularly vulnerable to inopportune light exposure as circadian disruption and sleep/wake disturbances are common after trauma (for examples see (Ayalon et al, 2007;Gaudet et al, 2018a;Gaudet et al, 2018b;Giannoccaro et al, 2013;Jain et al, 2004). We selected the cardiac arrest/cardiopulmonary resuscitation (CA) mouse model of global cerebral ischemia to test the hypothesis that light at night increases neuronal vulnerability because light at night creates a pro-inflammatory neuroenvironment (Bedrosian et al, 2013b; and inflammation is an important factor influencing the evolution of neurological damage after cerebral ischemia (Eltzschig and Eckle, 2011).…”

Section: Introductionmentioning

confidence: 99%

Dim light at night impairs recovery from global cerebral ischemia

Bedrosian

Zhang

Weil

et al. 2019

Experimental Neurology

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Nighttime lighting is one of the great conveniences of modernization; however, there is mounting evidence that inopportune light exposure can disrupt physiological and behavioral functions. Hospital patients may be particularly vulnerable to the consequences of light at night due to their compromised physiological state. Cardiac arrest/cardiopulmonary resuscitation (CA) was used to test the hypothesis in mice that exposure to dim light at night impairs central nervous system (CNS) recovery from a major pathological insult. Mice exposed to dim light at night (5 lux) had higher mortality in the week following cardiac arrest compared to mice housed in dark nights (0 lux). Neuronal damage was significantly greater in surviving mice exposed to dim light at night after CA versus those housed in dark nights. Dim light at night may have elevated neuronal damage by amplifying pro-inflammatory pathways in the CNS; Iba1 immunoreactivity (an indication of microglia activation) and pro-inflammatory cytokine expression were elevated in mice exposed to dim light at night post-CA. Furthermore, selective inhibition of IL-1β or TNFα ameliorated damage in mice exposed to dim light at night. The effects of light at night on CA outcomes were also prevented by using a wavelength of nighttime light that has minimal impact on the endogenous circadian clock, suggesting that replacing broad-spectrum nighttime light with specific circadian-inert wavelengths could be protective. Together, these data indicate that exposure to dim light at night after global cerebral ischemia increases neuroinflammation, in turn exacerbating neurological damage and potential for mortality.

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“…In various tissues including intact male or female rat spinal cord as well as male C57Bl6 mouse brain stem, cerebellum or liver transcript levels for most clock pathway mRNAs oscillate with a maximum amplitude at or around ZT0 and ZT12 [26] [8] (http://circadb.hogeneschlab.org/mouse, Supplementary Fig. S1 and S2).…”

Section: Resultsmentioning

confidence: 99%

Unaffected functional recovery after spinal cord contusions at different circadian times

Słomnicki

Wei

Burke

et al. 2021

Preprint

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The circadian rhythms of gene expression drive diurnal oscillations of physiological processes that determine the acute injury response including immunity, inflammation and hemostasis. While outcomes of various acute injuries are affected by the time of day at which the original insult occurred, such diurnal influences on recovery after spinal cord injury (SCI) are unknown. We report that several key regulators of circadian gene expression are differentially expressed in uninjured spinal cord tissue of naïve mice at Zeitgeber time 1 (ZT1) or ZT12, where ZT0 or ZT12 are times when lights are turned on or off, respectively. However, mice that received moderate, T9 contusive SCI at ZT0 or ZT12 showed similar recovery of locomotion as determined using the ladder walking test and the Basso mouse scale (BMS) over a 6 week post-injury period. Consistent with those findings, terminal histological analysis revealed no significant differences in white matter sparing at the injury epicenter. Therefore, locomotor recovery after thoracic contusive SCI is not affected by the time of day at which the neurotrauma occurred at least when comparing the beginning to the end of the mouse active period.

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Spinal Cord Injury in Rats Disrupts the Circadian System

Abstract: Visual Abstract

Cited by 34 publications

References 74 publications

Microglial ablation in rats disrupts the circadian system

Microglial ablation in rats disrupts the circadian system

Dim light at night impairs recovery from global cerebral ischemia

Unaffected functional recovery after spinal cord contusions at different circadian times

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