Traumatic brain injury (TBI) is a major cause of death and disability throughout the world with few pharmacological treatments available for individuals who suffer from neurological morbidities associated with TBI. Cellular and molecular pathological processes initiated at the time of injury develop into neurological impairments, with chronic sleep disorders (insomnia, hypersomnolence) being among the somatic, cognitive and emotional neurological impairments. Immediately post-injury, TBI patients report excessive daytime sleepiness, however, discordant opinions suggest that individuals should not be allowed to sleep or should be frequently awoken following brain injury. To provide adequate medical care, it is imperative to understand the role of acute post-traumatic sleep on the recovery of neurological function after TBI. The aim of this thesis was to examine post-traumatic sleep after experimental TBI, defined as an increase in sleep during the first hours post-injury. In these studies, we non-invasively measured sleep activity following diffuse brain injury induced by midline fluid percussion injury to examine the architecture of post-traumatic sleep in mice. We detected significant injury-induced increases in acute sleep for six hours regardless of injury severity or time of day injury occurred. We found concurrent increases in cortical levels of the sleep promoting inflammatory cytokine interleukin 1-beta. We extended the timeline of post-injury sleep recording and found increases in post-traumatic sleep are distinctly acute with no changes in chronic sleep following diffuse TBI. Further, we investigated if post-traumatic sleep was beneficial to neurological outcome after brain-injury by disrupting post-traumatic sleep. Disruption of post-traumatic sleep did not worsen functional outcome (neuromotor, sensorimotor, cognition) at one week after diffuse TBI. With sufferers of TBI not always seeking medical attention, our final studies investigated over-the-counter analgesics and their effect on post-traumatic sleep and functional outcome. Acute administration of analgesics with varying anti-inflammatory properties had little effect on post-traumatic sleep and functional outcome. Overall, these studies demonstrated translational potential and suggest sleep after a concussion is part of the natural recovery from injury. While disrupting sleep does not worsen outcome, it is in no way beneficial to recovery. Additionally, a single analgesic dose for pain management following concussion plays little role in short term outcome.

Puberty and adolescence are periods of brain-driven physiological development that display increased incidences of depression development. Adolescents display significant alterations to their stress response signaling, sleep patterns, and metabolism when compared to pre-pubescents. Increased exposure to stress, sleep disturbances, and impaired energy acquisition is typical during puberty and adolescence and similarly increases the likelihood of developing depression. A promising avenue of limiting the deleterious effects of stress and sleep disruption on pubertal and adolescent depressive behaviour is the use of treatments that blunt underlying metabolic impairments associated with depression. Treatments that directly or indirectly increase availability of the glucose metabolite L-lactate are associated with depression reduction. The investigations included in this dissertation evaluate the usability of L-lactate treatments in reducing depression development in pubertal CD-1 male and female mice. This work first examines a previously proposed oral lactate solution, its effect on energy substrate concentration and drowsiness, and its efficacy as a safe oral L-lactate treatment (Chapter 2). Subsequent research aimed to identify a pubertal model of depression that would allow future testing of L-lactate antidepressant treatment. Pubertal male and female mice exposed to chronic sleep disruption were evaluated for stress reactivity and depressive behavior and were identified as a model for antidepressant testing (Chapter 3). In the final study, we evaluated the effects of chronic sleep disruption on the expression of energy metabolites like L-lactate and glucose within the brain, its effect on neurotransmitters associated with depression, and changes to sleep architecture in relation to depression behaviour. Sleep disrupted and depressed animal models were administered L-lactate producing probiotics and were evaluated for improvements to energy substrate concentration, neurotransmitter expression, sleep recovery, and depression reduction (Chapter 4). The present thesis provides groundwork for the use of L-lactate therapies in depressed pubertal and adolescent groups and provides initial evaluations of probiotic intervention as a prevention strategy for juvenile depression.

ABSTRACT The two disorders of Restless Legs Syndrome (RLS) and Periodic Limb Movements (PLM) are well recognised as fairly common neurological disorders. The presentation is of a sensory and motor component suggestive of a state of hyperexcitability of the nervous system. The underlying abnormality is believed to involve a dopamine deficiency but many of characteristics of the disorders have not been adequately described or quantified. I investigated, firstly, the possible reasons for the gender bias in the prevalence studies and found that women were more likely to have some associated conditions which may be related to RLS as well as a higher symptom load when compared to men subjects with RLS. I then looked at the problems of analysing the sensations occurring in RLS. Due to the lack of an adequate measuring tool and the possibility of a relationship between the sensations of RLS and those of pain, I used a validated descriptive pain questionnaire (the McGill pain questionnaire) to measure the sensations of RLS. Subjects with RLS were able to describe the sensations with the pain questionnaire and severity indices calculated from the McGill correlated well with measures of RLS severity but not with other intensity measures for pain. In the area of motor events I investigated the possibility of creating a classification system for the muscle activations documented as PLM. I recorded multiple muscle groups in the legs during sleep and devised a classification using sequence of activation and timing of activations from the different muscles. I also used the classification to show subtle changes in the leg activation patterns associated with change in sleep stage.

SAMMANFATTNING Syftet med studien var att undersöka patienters inställning till att dela rum med patienter av motsatt kön och ålder. Metoden som användes var en deskriptiv tvärsnittsstudie med kvantitativ ansats som utfördes på två akutkirurgiska avdelningar. Det var 33 inneliggande patienter som deltog i studien. En studiespecifik enkät delades ut med tio frågor och två frågor om kön och ålder. Frågorna rörde olika synpunkter om hur det är att dela rum med andra patienter och om hur det är att dela rum med patienter med motsatt kön och ålder. Enkäten innehöll även en öppen fråga där deltagarna kunde lämna övriga synpunkter. Materialet analyserades med beskrivande statistik. För att jämföra skillnaden mellan män och kvinnor användes Mann Whitney U test och för att jämföra skillnader mellan de olika åldersgrupperna användes Kruskall Wallis. Resultatet visade att kvinnor ansåg att det var något obekvämare att dela rum med motsatt kön än vad det var för männen. Kvinnorna ville också i större utsträckning få information om detta innan man blev tilldelad en sal och plats. Den yngsta åldersgruppen 18-30 år upplevde sig mest besvärad av störd nattsömn jämfört med de två äldre grupperna. Slutsatsen var att kvinnor tyckte att det var mer obekvämt att dela rum med personer av motsatt kön. De yngsta deltagarna ansåg att det var mest besvärande att dela rum med andra och då med tanke på störd nattsömn. Det som skapade mest oro på patientsalen var när medpatienterna inte visade hänsyn eller om det var medicinskt oroliga. / ABSTRACT The aim of this study was to investigate the patient´s views on their expirience and preference of sharing a patient room with other patients of the opposite sex en age. The metod was a deskriptive cross-sectional study with a quantitavie analyxix. A survey was conducted at two surgical departments. The sample consisted of 33 inpatients. The investigation included questions of gender and age in order to compare differances between men and women and between age groups. The differences between sexes were analysed using Mann Whitney U test and the Kruskall Wallis test was used to determine differances between age groups. The results showed that women felt it somewhat inconvenient to share a room with the opposite sex than men did. The women would also like to receive information about this before the were assigned a room and place. the youngest age group of 18-30 years was the most troubled by disturbed sleep compared with the two older groups. The conclusion was that women found it more uncomfortable to share a room with people of the opposite sex. Among age groups the youngest participants experienced that it was most embarrassing to share a room with others and especially when considering distrubed sleep. What created the most concern was when the other patients did not show respect or if they were medically worried.

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<p><strong>Bakgrund:</strong> Människan tillbringar en tredjedel av sitt liv i sömn det är ett behov vilket hon inte kan vara utan. Patienter som vårdas på IVA drabbas frekvent av sömnstörningar och därmed sömnbrist. Tidigare gjorda studier tyder på att IVA patienter upplever sömnstörningar som ett stort problem.<strong> Syfte:</strong> Att beskriva sömnförändringar, sömnpåverkande faktorer och sömnförbättrande omvårdnadsåtgärder för IVA-patienter.<strong> Metod:</strong> Databassökning gjordes och nyckelord har identifierats. Studier som inkluderar vuxna patienter som vårdats på en IVA har valts för denna beskrivande litteraturstudie.<strong> Resultat:</strong> IVA-patienter drabbas av fragmenterad sömn uppdelad i korta abnorma perioder. Sömnen påverkas av mänsklig intervention, diagnostiska tester samt miljöbetingad ljus och ljud. Minskning av ljud- och ljusnivån samt sammanhängande vilotid utan intervention var de främst undersökta sömnfrämjande omvårdnadsåtgärder i de granskande artiklarna.<strong> Slutsats: </strong>Alla IVA-patienter upplevde störd sömnrytm. I vilken utsträckning sömnrytm stördes berodde på ålder, sjukdom, erfarenhet av IVA-vård och respiratorvård. Omvårdnadsåtgärder som planerad vilotid, sänkningar av ljud och ljus förbättrade sömnmönstret och skapade möjlighet till förbättrad sömn.</p>

Bakgrund: Människan tillbringar en tredjedel av sitt liv i sömn det är ett behov vilket hon inte kan vara utan. Patienter som vårdas på IVA drabbas frekvent av sömnstörningar och därmed sömnbrist. Tidigare gjorda studier tyder på att IVA patienter upplever sömnstörningar som ett stort problem. Syfte: Att beskriva sömnförändringar, sömnpåverkande faktorer och sömnförbättrande omvårdnadsåtgärder för IVA-patienter. Metod: Databassökning gjordes och nyckelord har identifierats. Studier som inkluderar vuxna patienter som vårdats på en IVA har valts för denna beskrivande litteraturstudie. Resultat: IVA-patienter drabbas av fragmenterad sömn uppdelad i korta abnorma perioder. Sömnen påverkas av mänsklig intervention, diagnostiska tester samt miljöbetingad ljus och ljud. Minskning av ljud- och ljusnivån samt sammanhängande vilotid utan intervention var de främst undersökta sömnfrämjande omvårdnadsåtgärder i de granskande artiklarna. Slutsats: Alla IVA-patienter upplevde störd sömnrytm. I vilken utsträckning sömnrytm stördes berodde på ålder, sjukdom, erfarenhet av IVA-vård och respiratorvård. Omvårdnadsåtgärder som planerad vilotid, sänkningar av ljud och ljus förbättrade sömnmönstret och skapade möjlighet till förbättrad sömn.

Self-injurious behavior (SIB) is a complex phenotype that occurs with an increasing prevalence of about 7-34% in humans and 10-12% in non-human primates (NHPs). This study evaluated the efficacy of probiotic Lactobacillus reuteri as a treatment for self-injurious behavior (SIB) and sleep disruption in rhesus macaques. The treatment was proposed to alleviate mild self-biting, sleep disruption, and reduce chronically elevated hypothalamic-pituitary-adrenocortical (HPA) axis activity, all hallmark features of monkeys with this condition. The probiotic preparation included two strains of L. reuteri (L. reuteri ATCC PTA 6475 & L. reuteri DSM 17938) containing on average 200 million colony forming units per chewable tablet. The study was conducted on 14 rhesus macaque monkeys (9 males) housed at the University of Massachusetts Amherst. To our knowledge this is the first time that a Lactobacillus strain has been used as a treatment for SIB in rhesus macaques. This study utilizes motion-activated infrared camera technology, modified enzyme-immunosorbent-assays (EIAs) techniques to measure hair cortisol concentrations, and daily behavioral observations to provide an overall assessment of the behavioral, physiological, and sleep associated implications of probiotic treatment on SIB and control non-human primates (NHPs). Administration of L reuteri modestly decreased biting behavior in monkeys with SIB (F(2,12) = 5.64, p= 0.02) and showed overall decrease in nighttime activity across all subjects but did not normalize SIB to nonSIB values. Hair cortisol values are pending. These findings and the findings of previous work further strengthen the argument for probiotics as an efficacious treatment for SIB behavior.