Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury

Abstract

Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague–Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14 days. Our results showed that 14 days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option.

Artificial Light at Night Increases Recruitment of New Neurons and Differentially Affects Various Brain Regions in Female Zebra Finches

“…Therefore, it could be that the finding in crows represents a transient stage of young, not matured neurons, which have not been incorporated yet in their final destinations. The increase in the number of new neurons that we had found is also opposite to the decrease that was found in nocturnal mammals under ALAN conditions [ 39 , 40 ] and supports our suggestion that ALAN affects nocturnal and diurnal species differently [ 8 ]. It is unlikely that this increase was mediated by a greater demand for spatial memory, since both groups were acclimated to their cages for three weeks prior to the onset of the experiment, and were kept there throughout ALAN exposure, until they were killed.…”

HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury via PI3K/AKT Pathway

“…Immunofluorescence staining was in accord with previous description (Li D. et al, 2016). After being blocked, coronal sections were incubated with anti-human nuclei antibody (MAB1281, 1:100, Millipore, Oxford, UK), myelin basic protein (MBP; 1:200; Santa Cruz Biotechnology, Dallas, TX, USA), Ki67 (1:200, Bioss, Beijing), DCX (1:200, Proteintech, China), or NeuN (1:200, Proteintech, China) at 4°C overnight and then incubated in Cy3/FITC-conjugated anti-mouse/rabbit anti IgG (1:500, Proteintech, China) for 1 h at room temperature, followed by DAPI (1:2,000, Biotech, China) staining for 10 min.…”

“…Propidium iodide (PI, Sigma-Aldrich Corporation, St. Louis, MO, USA) staining was performed to assess cell death (Li D. et al, 2016). Briefly, PI (10 mg/ml in saline, 0.4 mg/kg) was administered 1 h before killing by intraperitoneal injection in a total volume of not more than 100 μL.…”

Effects of crenolanib, a nonselective inhibitor of PDGFR, in a mouse model of transient middle cerebral artery occlusion

“…We randomly assigned mice to four groups: sham-operated mice treated with vehicle (Sham+vehicle), sham-operated mice treated with crenolanib (15 mg/kg, dissolved in 30% PEG-400+0.5% Tween-80+5% propylene glycol; Sham+crenolanib), MCAO mice treated with vehicle (MCAO+vehicle), and MCAO mice treated with crenolanib (MCAO+crenolanib). The MCAO+crenolanib group was divided into two subgroups: one was treated with crenolanib on days 1–3 and/or with 5-bromo-2′-deoxyuridine (BrdU, 50 mg/kg, Sigma-Aldrich, St Louis, MO, USA) (Wang et al, 2013) (Li et al, 2016) on days 1–7 after MCAO, and the second was treated with crenolanib on days 7–9 after MCAO. Vehicle, crenolanib, and BrdU were all administered into mice via intraperitoneal injection.…”