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To determine the effectiveness of a melatonin agonist for treating sleep disturbances in individuals with tetraplegia.Placebo-controlled, double-blind, crossover, randomized control trial.At home.Eight individuals with tetraplegia, having an absence of endogenous melatonin production and the presence of a sleep disorder. Interventions Three weeks of 8 mg of ramelteon (melatonin agonist) and 3 weeks of placebo (crossover, randomized order) with 2 weeks of baseline prior to and 2 weeks of washout between active conditions.Change in objective and subjective sleep.Wrist actigraphy, post-sleep questionnaire, Stanford sleepiness scale, SF-36.We observed no consistent changes in either subjective or objective measures of sleep, including subjective sleep latency (P = 0.55, Friedman test), number of awakenings (P = 0.17, Friedman test), subjective total sleep time (P = 0.45, Friedman test), subjective morning alertness (P = 0.35, Friedman test), objective wake after sleep onset (P = 0.70, Friedman test), or objective sleep efficiency (P = 0.78, Friedman test). There were significant increases in both objective total sleep time (P0.05, Friedman test), subjective time in bed (P0.05, Friedman test), and subjective sleep quality (P0.05, Friedman test), although these occurred in both arms. There were no significant changes in any of the nine SF-36 subscale scores (Friedman test, PsBonferroni adjusted α of 0.005).In this pilot study, we were unable to show effectiveness of pharmacological replacement of melatonin for the treatment of self-reported sleep problems in individuals with tetraplegia. Trial Registration ClinicalTrials.gov # NCT00507546.

Background Roughly, 10% of elderly patients develop postoperative cognitive dysfunction. General anesthesia impairs spatial memory in aged rats, but the mechanism is not known. Hippocampal neurogenesis affects spatial learning and memory in rats, and isoflurane affects neurogenesis in neonatal and young adult rats. We tested the hypothesis that isoflurane impairs neurogenesis and hippocampal function in aged rats. Methods Isoflurane was administered to 16-month-old rats at one minimum alveolar concentration for 4 h. FluoroJade staining was performed to assess brain cell death 16 h after isoflurane administration. Dentate gyrus progenitor proliferation was assessed by bromodeoxyuridine injection 4 days after anesthesia and quantification of bromodeoxyuridine+ cells 12 h later. Neuronal differentiation was studied by determining colocalization of bromodeoxyuridine with the immature neuronal marker NeuroD 5 days after anesthesia. New neuronal survival was assessed by quantifying cells coexpressing bromodeoxyuridine and the mature neuronal marker NeuN 5 weeks after anesthesia. Four months after anesthesia, associative learning was assessed by fear conditioning. Spatial reference memory acquisition and retention was tested in the Morris Water Maze. Results Cell death was sporadic and not different between groups. We did not detect any differences in hippocampal progenitor proliferation, neuronal differentiation, new neuronal survival, or in any of the tests of long-term hippocampal function. Conclusion In aged rats, isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome.

Nocturnal awakenings may constitute a unique risk for falls among older adults. We describe differences in gait and balance between presleep and midsleep testing, and whether changes in the lighting environment during the midsleep testing further affect gait and balance.Twenty-one healthy, late middle-aged and older (64.7 ± 8.0 y) adults participated in this repeated-measures design consisting of four overnight laboratory stays. Each night, participants completed baseline visual acuity, gait, and balance testing. After a 2-h sleep opportunity, they were awakened for 13 min into one of four lighting conditions: very dim white light (0.5 lux); dim white light (∼28.0 lux); dim orange light (∼28.0 lux); and white room-level light (∼200 lux). During this awakening, participants completed the same sequence of testing as at baseline.Low-contrast visual acuity significantly decreased with decreasing illuminance conditions (Balance and gait are impaired during midsleep awakenings among healthy, late middle-aged and older adults. This impairment is not ameliorated by exposure to room lighting, when compared to dim lights.

Background: Anesthetic agents cause cell death in the developing rodent brain and long-term, mostly hippocampal-dependent, neurocognitive dysfunction. However, a causal link between thesefindings has not been shown. Postnatal hippocampal neurogenesis affects hippocampal function into adulthood; therefore, the authors tested the hypothesis that isoflurane affects long-term neurocognitive function via an effect on dentate gyrus neurogenesis. Methods: The S-phase marker 5-bromodeoxyuridine was administered at various times before, during, and afte r4ho f isoflurane given to postnatal day (P)60 and P7 rats to assess dentate gyrus progenitor proliferation, early neuronal lineage selection, and long-term survival of new granule cell neurons. Fear conditioning and spatial reference memory was tested at various intervals from 2 weeks until 8 months after anesthesia. Results: In P60 rats, isoflurane increased early neuronal differentiation as assessed by BrdU/NeuroD costaining, decreased progenitor proliferation for 1 day, and subsequently increased progenitor proliferation 5‐10 days after anesthesia. In P7 rats, isoflurane did not induce neuronal lineage selection but decreased progenitor proliferation until at least 5 days after anesthesia. Isoflurane improved spatial reference memory of P60 rats long-term, but it caused a delayed-onset, progressive, persistent hippocampal deficit in P7 rats in fear conditioning and spatial reference memory tasks. Conclusion: The authors conclude that isoflurane differentially affects both neurogenesis and long-term neurocognitive function in P60 and P7 rats. Neurogenesis might mediate the long-term neurocognitive outcome after isoflurane at different ages.

Background: Millions of neonates undergo anesthesia each year. Certain anesthetic agents cause brain cell death and longterm neurocognitive dysfunction in postnatal day (P)7 rats. Despite its intuitive appeal, a causal link between cell death and neurocognitive decline after anesthesia has not been established. If one existed, the degree of cell death would be expected to correlate with the degree of neurocognitive dysfunction caused by anesthesia. The authors therefore tested if cell death caused by various durations of isoflurane at 1 minimum alveolar concentration causes duration-dependent long-term neurocognitive dysfunction. Methods: Isoflurane was administered to P7 rats at 1 minimum alveolar concentration for 0, 1, 2, or 4 h. To control for the respiratory depressant effects of anesthesia, a group of rats was treated wit h4ho fcarbon dioxide. Cell death was assessed by FluoroJade staining 12 h after the end of each intervention, and neurocognitive outcome was assessed 8 weeks later by using fear conditioning, spatial reference memory, and spatial working memory tasks. Results: Widespread brain cell death was caused b y2ha nd 4 h of isoflurane and b y4ho fcarbon dioxide. The degree and distribution of thalamic cell death was similar in 4 h isofluranetreated and 4-h carbon dioxide‐treated rats. Onl y4ho fisoflurane caused a long-term neurocognitive deficit affecting both spatial reference memory and spatial working memory. Working memory was improved in carbon dioxide‐treated rats. Conclusion: Isoflurane-induced brain cell death may be partly caused by hypercarbia. The inconsistencies between cell death and neurocognitive outcome suggest that additional or alternative mechanisms may mediate anesthesia-induced longterm neurocognitive dysfunction.