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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
71

Avaliação prospectiva de fatores prognósticos do traumatismo crânio encefálico / Prospective evaluation of prognostic factors of traumatic brain injury

Rosi Junior, Jefferson 22 August 2018 (has links)
Introdução: A lesão cerebral traumática decorrente do traumatismo crânio encefálico (TCE) é uma das principais causas de morte e incapacidade em todo o mundo. A estimativa do prognóstico é, por definição, um desafio multivariável. Objetivos: Estabelecer modelo prognóstico para avaliação das probabilidades de sobrevida após TCE com base nas características de admissão, incluindo lesões extracranianas, de doentes não sedados e estáveis quanto a hemodinâmica e respiração, apresentando tomografia de crânio com alterações. Doentes e Métodos: Um estudo de coorte avaliou 1275 doentes com TCE e tomografia do crânio (TC) anormais na admissão na unidade de emergência do HCFMUSP e analisou a mortalidade final. Realizou-se uma análise de regressão logística para determinar a relação de cada variável independente no desfecho final. Resultados: Quatro variáveis foram consideradas significativas no modelo: idade (anos), Escala de Coma de Glasgow (3-15), Escala de Marshall (estratificada em 2,3 ou 4,5,6, de acordo com o melhor grupo positivo (Valor preditivo) e anisocoria (sim / não). Obteve-se uma fórmula que está em um modelo logístico (USP índex do TCE) que estima a probabilidade de morte dos doentes de acordo com características da admissão. Conclusão: O modelo de probabilidade matemática (USP Index do TCE) é prático e acessível aos serviços de neurocirurgia. Foi criado para melhorar a qualidade da informação sobre a possibilidade de morte durante a hospitalização dos doentes acometidos pelo TCE, e pode ser aplicado pelos médicos para auxiliar à tomada de decisões / Introduction: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Estimation of prognosis is by definition a multivariable challenge. Objectives: The authors aimed to develop prognostic model for assessment of survival chances after TBI based on admission characteristics, including extracranial injuries of non-sedated and stable patients regarding hemodynamics and respiration, which would allow application of the model before in-hospital therapeutic interventions. Patients and Methods: 1275 patients were evaluated in a cohort study with TBI and abnormal CT scans upon admission to the emergency unit of Hospital das Clinicas of University of Sao Paulo. Mortality was analyzed as the final outcome. A logistic regression analysis was undertaken to determine the adjusted weigh of each independent variable in the outcome. Results: Four variables were found to be significant in the model: age (years), Glasgow Coma Scale (3-15), Marshall Scale (MS, stratified into 2,3 or 4,5,6; according to the best group positive predictive value) and anysochoria (yes/no). The formula in a logistic model (USP index to head injury) estimates the probability of death of patients according to characteristics that influence on mortality. Conclusion: The mathematical probability model (USP Index of TBI) is practical and accessible to neurosurgery services. It was created to improve the quality of information about the possibility of death during hospitalization of patients affected by the TBI and can be applied by doctors to aid in decision making
72

Preditores independentes de mortalidade em pacientes politraumatizados: estudo longitudinal, prospectivo, observacional / Independent predictors of mortality in polytrauma patients: a prospective, observational, longitudinal study

Luiz Guilherme Villares da Costa 03 August 2015 (has links)
O trauma constitui importante problema de saúde pública, com grande impacto sócio-econômico e muitas mortes. Visto que poucos pesquisadores traçam perfil epidemiológico e fatores preditores de óbito de forma integrada e prospectiva, este estudo foi idealizado com o objetivo de identificar preditores independentes de mortalidade em trauma e seu mapeamento populacional, visando melhorar o atendimento a politraumatizados graves. Após aprovação da comissão de ética em pesquisa institucional, estudo longitudinal, prospectivo e observacional foi conduzido entre 2010 e 2013 na região metropolitana da Grande São Paulo/Brasil com vítimas de politrauma grave (Injury Severity Score >15). A coleta de dados clínico-laboratoriais foi realizada em 4 momentos: 1- pré-hospitalar, 2- sala de emergência, 3- após 3 horas da admissão e 4- após 24 hs da admissão. O desfecho principal foi mortalidade em 30 dias. Os dados foram analisados com teste t de Student ou Mann-Whitney, ANOVA não paramétrica, e Equações de Estimação Generalizadas (EEG) para medidas repetidas (p < 0,05). A população total do estudo foi de 334 pacientes, sendo excluídos 124 por não adequação ao protocolo e incluídos 200 indivíduos na análise final. Os preditores independentes de mortalidade encontrados foram: saturação arterial de oxigênio de hemoglobina (OR=0,989; IC 95% 0,982-0,995- p < 0,001), pressão arterial diastólica (OR=0,998; IC 95% 0,995-0,998- p < 0,001), nível sérico de lactato (OR=1,046; IC 95% 1,012-1,082- p < 0,004), pontuação na escala de coma de Glasgow (OR=0,973;IC 95% 0,965-0,982-p < 0,001), quantidade de cristalóides infundidos (OR=1,013; IC 95% 1,000-1,025- p < 0,023 - a cada 1000 ml). Através das análises realizadas neste estudo foi possível concluir que os preditores independentes de mortalidade foram: hipoxemia, hipotensão arterial diastólica, hiperlactatemia, baixa pontuação na escala de coma de Glasgow e aumento de volume de cristalóides infundidos / Trauma is an important public health problem, with high socioeconomic impact and major adverse clinical outcomes. The epidemiological profile and predictors of death in trauma patients have not been addressed in an integrated and prospective way. Therefore, the present study was designed to identify independent predictors of mortality in trauma patients and their populational mapping to improve the care of severe polytrauma patients. After approval by the ethics in institutional research committee, the present longitudinal, prospective and observational study was conducted between 2010 and 2013 in the metropolitan area of São Paulo/Brazil with victims of severe polytrauma (Injury Severity Score >15). The collection of clinical and laboratory data was performed at 4 different time points: 1, pre-hospital; 2, in the emergency room; 3, at 3 hours after admission; and 4, at 24 hours after admission. The primary outcome was mortality within 30 days. The data were analyzed with Student\'s t-test or the Mann-Whitney test, nonparametric ANOVA and Generalized Estimating Equations (GEE) for repeated measures (p < 0.05). The total study population consisted of 334 patients. In total, 124 patients were excluded for not fitting the protocol, and 200 individuals were included in the final analysis. The independent predictors of mortality were as follows: arterial hemoglobin oxygen saturation (OR=0.989, 95% CI 0.982-0.995, p < 0.001); diastolic blood pressure (OR=0.998, 95% CI 0.995-0.998, p < 0.001); serum lactate level (OR=1.046, 95% CI 1.012- 1.082, p < 0.004); score on the Glasgow coma scale (OR=0.973, 95% CI 0.965-0.982, p < 0.001); and the amount of infused crystalloid (OR=1.013, 95% CI 1.000-1.025, p < 0.023 - each 1000 ml). Through the analyses performed in this study, it was concluded that the independent predictors of mortality at any given time were as follows: hypoxemia; diastolic arterial hypotension; hyperlactatemia; a low score on the Glasgow coma scale; and volume of infused crystalloid
73

Couples' experiences after a traumatic brain injury : a mixed-method synthesis and qualitative study

Chadwick, Nicole January 2018 (has links)
Background: Traumatic brain injuries (TBIs) can result in a number of consequences for those who has sustained the injuries, as well as having an impact on their wider system. Estimates of divorce and relationship dissolution among couples following TBI can be as high as 54% and partners are reported to experience high levels of stress. The majority of studies have explored couples' relationships following TBI from the perspective of either the person with TBI or the partner, as opposed to exploring this dyadically and, therefore, limiting the holistic understanding to this topic. Aim: The two aims of this thesis are as follows: firstly, the mixed-method synthesis review aimed to explore the current dyad evidence-base around couples' experiences and relationships following TBI; and secondly, the qualitative study aimed to explore the impact of TBI on couples' experiences and relationships. Method: The systematic review's search strategy consisted of a computerised search across five databases and manual searches for further references in other relevant literature reviews and reference lists. The quality of the qualitative and quantitative studies were analyses separately. Metaethnography was employed to synthesize the finding from the qualitative studies. In the qualitative empirical study, five dyad-couples participated in the semi-structured interviews. The individuals with TBI and their partners were interviewed independently. The data collected was analysed using a combined deductive-inductive framework analysis approach, which supported comparisons between and within couples. Results: The systematic review yielded eight eligible studies, three quantitative and five qualitative studies. Review of the quantitative studies suggested couples reported poor relationship quality and partners reported more dyadic dissatisfaction and overall poorer relationship adjustment than the people with TBI. Analysis of the qualitative studies suggested there were significant variations in the way couples' experience and respond to TBI. This included individual responses from the people with TBI, their partners or collectively as a couple, which influenced their relationship dynamics and also how they coped. The findings also drew attention to other contextual factors that influenced couples' attributions and perceptions toward the TBI-related changes. Deductive and inductive analysis of the interviews in the qualitative empirical study identified three overarching themes: 'You begin to realise that, actually, life may not be the same ever [again]...'; perceived influences on relationship endurance following TBI; and contextual and other factors. These explored the impact of TBI on couples' relationships and the processes that interacted with or influenced their perceived relationship endurance. Conclusion: Although limited by a small number of eligible studies in the systematic review and small sample size in the qualitative empirical study, this thesis emphasized the importance of dyadic research for gaining a holistic understanding of couples' experiences and relationships following TBI. This allows the complex interplay between the TBI, the person who has suffered the TBI, their partner and their relationship to be better understood. The interconnectedness between the individuals and how the difficulties are experienced raises possible issues for healthcare services around their views and approaches to the individual with TBI, their partner and the couple's relationship during the recovery and rehabilitation journey.
74

Attention and memory/learning following pediatric traumatic brain injury a multidimensional pilot study /

Bongiolatti, Susan Renee. January 2003 (has links)
Thesis (M.S.)--University of Florida, 2003. / Title from title page of source document. Includes vita. Includes bibliographical references.
75

Traumatic brain injuries and whiplash injuries : epidemiology and long-term consequences

Styrke, Johan January 2012 (has links)
Background The incidence of traumatic brain injuries (TBI) is about 500 cases per 100,000 inhabitants per year, a majority of which are mild TBI (MTBI). The incidence of whiplash injuries is about 300/100,000/year. There are several similarities between MTBI and whiplash injuries with regard to the causes of injury (traffic crashes and falls), the demographic profile of the injured (mostly young persons), and the type of symptoms exhibited by some of the injured (for example head/neck pain, fatigue, irritability, impaired cognitive functioning, and depression).  Main aim To investigate the epidemiology and long-term consequences in terms of symptoms, disability, and life satisfaction in cases of TBI and whiplash injuries in a well-defined population. Material and methods Data on frequencies and characteristics of TBI and whiplash injuries were extracted from the injury database at the emergency department (ED) of Umeå University Hospital (UUH). The results were presented as descriptive epidemiology. The 18-65 year-old persons who sustained an MTBI or whiplash injury in 2001, were provided a questionnaire three and five years after injury respectively, in which questions were asked about: Symptoms; Rivermead Post Concussion Symptoms Questionnaire (RPQ) Disability; Rivermead Head Injury Follow Up Questionnaire (RHFUQ) Life satisfaction; LiSat-11 A local reference population was used for comparison of the RPQ. A national cohort was used as reference for LiSat-11. Data on sick leave for the cases of whiplash injuries were analysed to calculate the cost to society for loss of productivity. Results In 2001, the incidence of TBI was 354/100,000/year. The mean age was 23 and 55% were men. Ninety-seven percent of the injuries were classified as mild (Glasgow coma scale 13-15). The main causes were falls (55%) and traffic related injury events (30%). In 8% of the cases (17% of the elderly persons) an intracranial bleeding was detected by using CT. The 3-year follow-up of the MTBI patients showed that women had more symptoms and disability (~50%) than men (~30%). Both women and men had more symptoms and lower life satisfaction compared with the reference population. The incidence of traffic-related whiplash injuries in adults was 235/100,000/year and the annual incidences were relatively stable during 2000-2009. Combining the incidences with national insurance data showed that the proportion of insurance claims decreased during the period. When looking at whiplash trauma following all causes of injury in 2001, traffic crashes caused 61% of the injuries and falls caused 14%. Neck fractures occurred in 3% of the cases. Five years after whiplash injury, the injured persons had more symptoms and lower life satisfaction than the references. Sick leave ≥15 days was granted in 14% of the cases of whiplash injuries. The median number of sick days was 298 and the cost of loss of productivity during the follow-up was 5.6 million USD. The frequencies of symptoms were relatively alike when comparing subjects with whiplash injuries to subjects with MTBI. Conclusion TBI and whiplash injuries are common, especially among young people, and the injuries render long-term symptoms, disability, and impaired life satisfaction in up to 50% of the cases. Symptoms exhibited are alike between the two types of injuries. The cost to society for loss of productivity is high, and there is a need for enhanced preventive measures aiming at reducing traffic-related injuries, sports injuries, alcohol-related injuries, and falls. Physical, mental, and social factors are important and should be addressed when examining and treating patients with persisting symptoms following TBI and whiplash injuries. / Bakgrund Skallskador utgör ett stort folkhälsoproblem, särskilt eftersom många som skadas är unga. Skallskador är också, parallellt med självmord, den vanligaste dödsorsaken hos ungdomar och unga vuxna. De flesta av skadorna klassas som ”lätta” i akutskedet men trots det så kommer en del av patienterna att drabbas av kvarstående besvär, t ex smärta, koncentrationssvårigheter, depression och nedsatt livstillfredsställelse. Whiplashskador är nästan lika vanligt förekommande som skallskador och uppkommer framförallt i trafikolyckor. Även fall- och sportskador orsakar emellertid ett betydande antal whiplashskador. I normalfallet avtar de akuta symptomen inom några veckor men en del av patienterna anger att de får kvarstående besvär. Ett flertal skademekanismer i nackens vävnader är kända men tyvärr svåra att verifiera eller utesluta. Huvudsyfte Att undersöka förekomsten av skallskador och whiplashskador i en väldefinierad population samt beskriva restsymptom, funktions-nedsättningar och livstillfredsställelse hos de drabbade tre till fem år efter skadan. Material och metod Förekomsten av skadorna (Studie I, III och IV) Studierna baseras på skadedatabasen vid Norrlands Universitetssjukhus i Umeå (NUS). I skadedatabasen registreras alla patienter som söker till akutmottagningen efter en skadehändelse, ca 10 000 fall per år. När patienterna anmäler sig i receptionen tilldelas de en skadejournal som de själva fyller i i väntan på att bli undersökta. När patienter inkommer med svårare skador får anhöriga i möjligaste mån fylla i journalen. Primärvårdens jour har under åren för studiens genomförande varit belägen på akutmottagningen under kvällar, nätter och helger vilket inneburit att de få skadefall som konsekvent missats har varit lättare skador som behandlats dagtid på vårdcentralerna i upptagningsområdet.   Långtidsuppföljning (Studie II, III och V) En uppföljande enkätundersökning bestående av ett antal validerade frågeformulär skickades till alla skall- och whiplashskadade patienter i arbetsför ålder tre respektive fem år efter skadehändelsen. De frågeformulär som analyserades var: För symptom: Rivermead Post Concussion Symptoms Questionnaire (RPQ) För funktionsnedsättning: Rivermead Head Injury Follow Up Questionnaire (RHFUQ) För livstillfredsställelse: Life Satisfaction-11 (LiSat-11) För smärta (hos de whiplashskadade): Visual Analogue Scale (VAS)  Resultaten från RPQ och LiSat-11 jämfördes med sedan tidigare tillgängligt material från åldersmatchade referenspopulationer. När det gäller de whiplashskadade genomfördes en femårsuppföljning avseende sjukskrivning. Data från Försäkringskassan analyserades och samhällskostnaden för produktionsbortfall beräknades baserat på den genomsnittliga kostnaden för en årsarbetare. Resultat Förekomsten av skallskador vid NUS under 2001 var 354 skadade per 100 000 invånare. Medelåldern på de skadade var 23 år och 55% var män. Andelen lätta skallskador var 97%. Fallolyckor orsakade flest skador (55%) och trafikolyckor var näst vanligast (30%). Minst 17% av patienterna (ofta medelålders personer) var alkoholpåverkade. Hos 8% av patienterna (17% av personer över 65 år) upptäcktes blödningar i hjärnan. I uppföljningen efter tre år noterades att de skallskadade patienterna i arbetsför ålder hade högre symptomfrekvens och lägre livstillfredsställelse än referenspopulationerna. Kvinnorna rapporterade högre förekomst av symptom och funktionsnedsättning än männen. Funktionsnedsättning av varierande grad samt så kallat postkommotionellt syndrom (med förekomst av minst tre specificerade symptom) fanns hos ca 50% av kvinnorna och hos ca 30% av männen. Medelförekomsten av whiplashskador till följd av trafikolyckor var under 2000-2009 235 fall per 100 000 invånare och år. Sammantaget var förekomsten relativt stabil under perioden; en ökning med 1% per år noterades. När siffrorna matchades mot data från Försäkringsförbundet noterades en minskning av andelen försäkringsärenden under perioden. 2001 års incidens av akuta whiplashskador efter alla typer av skadehändelser var 383 skadade per 100 000 invånare. Könsfördelningen var 56% män / 44% kvinnor och medelåldern var 32 år. Trafikolyckor orsakade 61% av whiplashskadorna medan fallolyckor stod för 14%. Frakturer i nacken var ovanliga och hittades hos 3% av patienterna. I femårsuppföljningen av whiplashpatienter i arbetsför ålder noterades att de hade högre frekvens (ca 50%) av symptom samt lägre livstillfredsställelse än referenspopulationerna. Funktionsnedsättning av varierande grad fanns hos ca 50% av patienterna. Kvinnorna skattade sin smärta högre än männen men i övrigt fanns ingen könsskillnad beträffande förekomsten av symptom, funktionsnedsättning och livstillfredsställelse. Vid jämförelse mellan whiplashskadade och skallskadade noterades att förekomsten av symptom med några få undantag inte skilde sig åt mellan grupperna. Fjorton procent av de whiplashskadade blev sjukskrivna i mer än 14 dagar. Sjukskrivningens medianlängd var 298 dagar och i 3% av fallen fortskred sjukskrivningen under hela 5-årsperioden. Trafikskadade sjukskrevs oftare än fallskadade och noterbart är också att nackfrakturer ej resulterade i längre sjukskrivningar än mjukdelsskador. Samhällskostnaden för produktionsbortfall var i snitt ca 600 000 kr per sjukskrivning. Konklusion Avhandlingen bidrar med nya grunddata som ytterligare förstärker bilden av att skallskador och whiplashskador är vanliga och att det framförallt är unga personer som drabbas. Grad och typ av kvarstående besvär är likartade efter båda skadetyper. Samhällskostnaden för skadorna är hög och lämpliga områden för skadepreventivt arbete tycks vara fallskadeprevention, trafikskadeprevention, skadeprevention inom hästsport, fotboll och ishockey samt prevention av alkoholrelaterade skador. Både fysiska, psykologiska och sociala faktorer inverkar på läkningsförloppet och symptombilden efter skadorna och det är viktigt att utvärdera och behandla patienterna med utgångspunkt från detta.
76

Cognitive Behaviour Therapy after Acquired Brain Injury: An Investigation of the Benefits for Emotional Well-being, Coping Strategy Use, and Community Integration at 6-Months Post-Treatment

Arundine, April 15 December 2009 (has links)
Objectives: To demonstrate that at 6-months post-cessation of cognitive behaviour therapy (CBT) adapted for acquired brain injury (ABI), (1) patients maintain psychological benefits, (2) coping strategy selection improves, (3) community integration is enhanced, and (4) benefits are observed in both face-to-face and telephone administrations. Methods: Participants. Seventeen ABI patients with elevated psychological distress. Outcome Measures. Pre-treatment, post-treatment and 6-month follow-up performance on the Symptom Checklist-90-revised (SCL-90-R), Depression, Anxiety Stress Scales (DASS-21), Community Integration Questionnaire (CIQ) and the Ways of Coping-Revised Questionnaire (WOC-R). Procedures. Eleven CBT sessions provided in group, face-to-face format or individually by telephone. Results: For face-to-face and telephone groups, psychological distress was significantly reduced from pre-treatment to 6-months follow-up: DASS-21 (t16= 7.32, p <.000); SCL-90-R (t16= 6.22, p <.000). Community integration (t16= -6.15 p<.000) and problem-focused coping (t16= -3.67, p<.01) were also significantly enhanced. Conclusion: CBT adapted for patients with ABI carries robust benefits even 6-months after treatment.
77

Cognitive Behaviour Therapy after Acquired Brain Injury: An Investigation of the Benefits for Emotional Well-being, Coping Strategy Use, and Community Integration at 6-Months Post-Treatment

Arundine, April 15 December 2009 (has links)
Objectives: To demonstrate that at 6-months post-cessation of cognitive behaviour therapy (CBT) adapted for acquired brain injury (ABI), (1) patients maintain psychological benefits, (2) coping strategy selection improves, (3) community integration is enhanced, and (4) benefits are observed in both face-to-face and telephone administrations. Methods: Participants. Seventeen ABI patients with elevated psychological distress. Outcome Measures. Pre-treatment, post-treatment and 6-month follow-up performance on the Symptom Checklist-90-revised (SCL-90-R), Depression, Anxiety Stress Scales (DASS-21), Community Integration Questionnaire (CIQ) and the Ways of Coping-Revised Questionnaire (WOC-R). Procedures. Eleven CBT sessions provided in group, face-to-face format or individually by telephone. Results: For face-to-face and telephone groups, psychological distress was significantly reduced from pre-treatment to 6-months follow-up: DASS-21 (t16= 7.32, p <.000); SCL-90-R (t16= 6.22, p <.000). Community integration (t16= -6.15 p<.000) and problem-focused coping (t16= -3.67, p<.01) were also significantly enhanced. Conclusion: CBT adapted for patients with ABI carries robust benefits even 6-months after treatment.
78

The expression and function of phosphacan/RPTP[beta] in adaptive synaptogenesis after traumatic brain injury

Harris, Janna L. January 1900 (has links)
Thesis (Ph.D.)--Virginia Commonwealth University, 2008. / Prepared for: Dept. of Anatomy and Neurobiology. Title from title-page of electronic thesis. Bibliography: leaves 181 - 202. Available online via the Internet.
79

Anxiety in the aftermath of acquired brain injury : prevalence, course and correlates

Genis, Michelle January 2013 (has links)
This study aimed to determine the prevalence of anxiety specifically related to discharge in a group of 42 individuals who had sustained moderate to severe acquired brain injury and who were imminently due to return home following a period of inpatient neurorehabilitation. The study also aimed to explore differential relationships between psychological factors (self-efficacy and health control beliefs) alongside the relative influence of demographic (age, gender and ethnicity) and clinical (medical diagnosis and injury location) characteristics on discharge-anxiety. A cross-sectional, single-group design was employed, wherein correlational and multivariate analyses were used to explore relationships between variables. Data was obtained via self-report tools and retrospective reviews of medical files. While few participants (14%) reported markedly elevated trait-anxiety almost half (45%) of the sample reported levels of transient, state-anxiety which could be considered to be clinically significant. Notably, state-anxiety (appraised via the State-Trait Anxiety Inventory) was strongly associated with discharge-anxiety (appraised via the Patient Anxieties Questionnaire). Age, self-efficacy and internal health control beliefs made independent contributions to the level of discharge-anxiety reported, with perceived self-efficacy alone explaining 69% of the overall variance and mediating the effect of internal control beliefs. No other demographic or clinical characteristics examined were significantly related to discharge-anxiety. Although causality cannot be inferred, findings suggest that discharge-related anxiety is best predicted by poor perceptions of self-efficacy. Implications for clinical practice and directions for future research are discussed.
80

Investigating a role for the ATP-binding cassette transporters A1 and G1 during synaptic remodeling in the adult mouse

Pearson, Vanessa. January 2007 (has links)
Glial-derived lipoparticles facilitate the transport of cholesterol and lipids between cells within the CNS and have been shown to support neuronal growth and synaptogenesis. Partial deafferentation of the hippocampus by unilateral entorhinal cortex lesioning (uECL) induces well-described cytoarchitectural reorganisation and reactive sprouting in the dentate gyrus (DG). Previous studies have demonstrated a dynamic regulation of cholesterol homeostasis in the hippocampus following deafferentation, and suggest that mechanisms facilitating cholesterol transport are important during reinnervation. Furthermore, there is growing evidence that statins, a family of cholesterol-lowering drugs which inhibit the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA-R), may confer neuroprotection following trauma. / The ATP binding cassette transporters (ABC) A1 and G1 assist the generation of lipoparticles by mediating cholesterol and phospholipid efflux to extracellular apolipoprotein E (APOE), the brain's primary lipoprotein. To examine a role for these transporters in the regulation of cholesterol efflux during synaptic remodelling, and the effects of low-dose pravastatin (a potent HMGCoA-R inhibitor) on such intercellular transport mechanisms, we measured the expression of ABCA1, ABCG1, APOE, apoE(LDL)R and HMGCoA-R in the hippocampus of saline and pravastatin treated mice over time following uECL. It is shown here that ABCA1 and not ABCG1 is up-regulated at the level of mRNA and protein expression, along with APOE, in the hippocampus during active regeneration (14DPL) as determined by histochemical analysis of acetylcholinesterase staining density in the DG. While pravastatin treatment was observed to differentially influence the expression of ABCA1 mRNA and protein over time, no effects on APOE or ABCG1 mRNA expression were observed following uECL. Additionally, HMGCoA-R mRNA expression was significantly down-regulated at 21 DPL in the deafferented hippocampus in pravastatin-treated animals. While the low-dose pravastatin treatment applied here was sufficient to inhibit HMGCoA-R activity in the liver, enzymatic activity was unaffected in the cortex. / These findings suggest that ABCA1 and not ABCG1 may be important in the APOE-mediated cholesterol recycling observed during the active phase of neural reinnervation in response to uECL. In addition, the results presented here suggest that the administration of clinically-relevant statin therapy may be sufficient to influence the regulation of cerebral cholesterol homeostasis following trauma in the adult mouse brain.

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