Objective: To describe the prevalence and impact of vestibular dysfunction and nonspecific dizziness diagnoses and explore their associations with traumatic brain injury (TBI) severity, mechanism, and postconcussive comorbidities among post-9/11 veterans. Setting: Administrative medical record data from the US Departments of Defense and Veterans Affairs (VA). Participants: Post-9/11 veterans with at least 3 years of VA care. Design: Cross-sectional, retrospective, observational study. Main Measures: International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for TBI, vestibular dysfunction, dizziness, and other commonly associated postconcussive conditions; Neurobehavioral Symptom Inventory. Results: Of the 570 248 post-9/11 veterans in this sample, 0.45% had a diagnosis of vestibular dysfunction and 2.57% had nonspecific dizziness. Those with either condition were more likely to have evidence of TBI (57.11% vs 28.51%) and reported more disruption from neurobehavioral symptoms. Blast and nonblast injuries were associated with greater symptom disruption, particularly in combination. Conclusions: There was a consistent, significant association between TBI and vestibular dysfunction or nonspecific dizziness, after controlling for sociodemographic factors, injury mechanism, and comorbid conditions. Given that most deployed post-9/11 veterans report blast and/or nonblast injuries, the need for prompt identification and management of these conditions and symptoms is clear.

In this research study, the correlation and significance of head injuries in adult sex offenders that have committed crimes against children were measured and compared to a group of criminal offenders that have committed non-sex-related criminal offenses. Data on 30 randomly selected individuals from each of the two groups (60 individuals total) were collected to measure and compare the number of individuals with a head injury in each group. The purpose of this research was to gain a better understanding of why criminally deviant behaviors occur in adults. This research also hoped to encourage further research on this topic or similar topics that can lead to new ideas in prevention, intervention, and treatment plans in sex offenders.

No description available.

INTRODUÇÃO: Em pacientes vítimas de trauma crânio-encefálico é fundamental que se restabeleça a volemia intravascular, quando associado à hipotensão arterial, com o intento de manter a pressão de perfusão e não agravar a lesão do sistema nervoso central. A hipovolemia pode ser corrigida com infusão rápida de soluções cristalóides e/ou colóides, quando hemoderivados não estão disponíveis. Nesta condição, o hematócrito (Ht) pode reduzir-se para valores muito baixos. A anemia aguda altera a viscosidade do sangue e pode interferir na reatividade vascular encefálica. O objetivo deste estudo foi avaliar a pressão intracraniana(PIC) na presença de lesão criogênica encefálica, quando se realiza hemodiluição aguda com Ringer lactato ou hidroxietilamido 450/0,7 a 6%, estabelecendo-se como meta reduzir o hematócrito de 40% para 35% ou para 27%. MÉTODOS: Foram utilizados 35 cães machos sem raça definida, cujo hematócrito inicial era superior a 40%, anestesiados e submetidos à lesão encefálica criogênica durante 20 minutos. Após foram aleatoriamente distribuídos em 5 grupos experimentais: HES35, hemodiluídos com hidroxietilamido até Ht de 35%; RL35, hemodiluídos com Ringer lactato até Ht de 35%; HES27, hemodiluídos com hidroxietilamido até Ht de 27%; RL 27, hemodiluídos com Ringer lactato até Ht de 27%; e controle, sem hemodiluição. As variáveis hemodinâmicas sistêmicas foram obtidas por meio de cateter de artéria pulmonar; a PIC foi medida por sensor introduzido no espaço subaracnóideo no hemisfério contralateral à lesão criogênica; as variáveis laboratoriais foram obtidas de amostras de sangue arterial. RESULTADOS: A lesão criogênica encefálica levou a aumento da PIC em todos os animais, sem diferença entre os grupos(p>0,5). Este aumento foi exacerbado somente nos animais hemodiluídos até hematócrito de 27%(p<0,03). A solução utilizada não influenciou o comportamento da PIC(p>0,5). / Objective: Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over optimal fluid management for these patients. This study aimed to investigate the effects of acute hemodilution with hydroxyethyl starch (HES) or lactated Ringer\'s solution (LR) in intracranial pressure(ICP) and cerebral perfusion pressure in dogs submitted to a cryogenic brain injury model. Design: Prospective laboratory animal study. Setting: Research laboratory in a teaching hospital. Subjects: Thirty-five male mongrel dogs. Interventions: Animals were enrolled to 5 groups: control, hemodilution with lactated Ringer\'s solution (RL) or hydroxyethyl starch (HES) 6% to an hematocrit target of 27% or 35%. Measurements and Main Results: ICP and CPP levels were measured after cryogenic brain injury. Hemodilution promotes an increment of ICP levels, which decreases CPP when hematocrit target was estimated in 27% after hemodilution. However, no differences were observed regarding crystalloid or colloid solution used for hemodilution in ICP and CPP levels. Conclusions: Hemodilution to a low hematocrit level increases ICP and decreases CPP scores in dogs submitted to a cryogenic brain injury. These results suggest that excessive hemodilution to a hematocrit below 30% should be avoided in traumatic brain injury patients.

INTRODUÇÃO: Em pacientes vítimas de trauma crânio-encefálico é fundamental que se restabeleça a volemia intravascular, quando associado à hipotensão arterial, com o intento de manter a pressão de perfusão e não agravar a lesão do sistema nervoso central. A hipovolemia pode ser corrigida com infusão rápida de soluções cristalóides e/ou colóides, quando hemoderivados não estão disponíveis. Nesta condição, o hematócrito (Ht) pode reduzir-se para valores muito baixos. A anemia aguda altera a viscosidade do sangue e pode interferir na reatividade vascular encefálica. O objetivo deste estudo foi avaliar a pressão intracraniana(PIC) na presença de lesão criogênica encefálica, quando se realiza hemodiluição aguda com Ringer lactato ou hidroxietilamido 450/0,7 a 6%, estabelecendo-se como meta reduzir o hematócrito de 40% para 35% ou para 27%. MÉTODOS: Foram utilizados 35 cães machos sem raça definida, cujo hematócrito inicial era superior a 40%, anestesiados e submetidos à lesão encefálica criogênica durante 20 minutos. Após foram aleatoriamente distribuídos em 5 grupos experimentais: HES35, hemodiluídos com hidroxietilamido até Ht de 35%; RL35, hemodiluídos com Ringer lactato até Ht de 35%; HES27, hemodiluídos com hidroxietilamido até Ht de 27%; RL 27, hemodiluídos com Ringer lactato até Ht de 27%; e controle, sem hemodiluição. As variáveis hemodinâmicas sistêmicas foram obtidas por meio de cateter de artéria pulmonar; a PIC foi medida por sensor introduzido no espaço subaracnóideo no hemisfério contralateral à lesão criogênica; as variáveis laboratoriais foram obtidas de amostras de sangue arterial. RESULTADOS: A lesão criogênica encefálica levou a aumento da PIC em todos os animais, sem diferença entre os grupos(p>0,5). Este aumento foi exacerbado somente nos animais hemodiluídos até hematócrito de 27%(p<0,03). A solução utilizada não influenciou o comportamento da PIC(p>0,5). / Objective: Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over optimal fluid management for these patients. This study aimed to investigate the effects of acute hemodilution with hydroxyethyl starch (HES) or lactated Ringer\'s solution (LR) in intracranial pressure(ICP) and cerebral perfusion pressure in dogs submitted to a cryogenic brain injury model. Design: Prospective laboratory animal study. Setting: Research laboratory in a teaching hospital. Subjects: Thirty-five male mongrel dogs. Interventions: Animals were enrolled to 5 groups: control, hemodilution with lactated Ringer\'s solution (RL) or hydroxyethyl starch (HES) 6% to an hematocrit target of 27% or 35%. Measurements and Main Results: ICP and CPP levels were measured after cryogenic brain injury. Hemodilution promotes an increment of ICP levels, which decreases CPP when hematocrit target was estimated in 27% after hemodilution. However, no differences were observed regarding crystalloid or colloid solution used for hemodilution in ICP and CPP levels. Conclusions: Hemodilution to a low hematocrit level increases ICP and decreases CPP scores in dogs submitted to a cryogenic brain injury. These results suggest that excessive hemodilution to a hematocrit below 30% should be avoided in traumatic brain injury patients.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

No description available.

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

by Ho Wai Fong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 207-243). / Abstracts in English and Chinese. / Title --- p.i / Abstract --- p.ii / 摘要 --- p.v / Acknowledgements --- p.viii / Table of Contents --- p.x / List of Abbreviations --- p.xviii / List of Figures --- p.xxiv / List of Tables --- p.xxix / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Traumatic brain injury --- p.1 / Chapter 1.2 --- Ceils of the nervous system: glia --- p.1 / Chapter 1.2.1 --- Astroglia - / Chapter 1.2.1.1 --- Molecular markers of astroglia --- p.3 / Chapter 1.2.1.2 --- Functions of astroglia --- p.3 / Chapter 1.2.2 --- Oligodendrocyte --- p.5 / Chapter 1.2.2.1 --- Molecular markers of oligodendrocyte --- p.6 / Chapter 1.2.2.2 --- Functions of oligodendrocyte --- p.6 / Chapter 1.2.3 --- Microglia --- p.7 / Chapter 1.2.3.1 --- Molecular markers of microglia --- p.7 / Chapter 1.2.3.2 --- Functions of microglia --- p.8 / Chapter 1.3 --- Cytokine and brain injury --- p.8 / Chapter 1.4 --- Tumor necrosis factor alpha (TNF-α) --- p.9 / Chapter 1.5 --- TNF-α receptor --- p.10 / Chapter 1.6 --- Biological activities of TNF-α --- p.11 / Chapter 1.7 --- Signaling mechanism --- p.13 / Chapter 1.7.1 --- Protein kinase C --- p.13 / Chapter 1.7.2 --- Protein kinase A --- p.14 / Chapter 1.7.3 --- p38 mitogen-activated protein kinase (p38 MAPK) --- p.15 / Chapter 1.7.3.1 --- Biological activities of p38 MAPK --- p.18 / Chapter 1.7.4 --- Inducible nitric oxide synthase (iNOS) --- p.20 / Chapter 1.7.5 --- cAMP responsive element binding protein (CREB) --- p.21 / Chapter 1.7.6 --- Transcription factor c-fos --- p.23 / Chapter 1.7.7 --- Nuclear factor kappa-B (NF-kB) --- p.24 / Chapter 1.8 --- "Brain injury, astrogliosis and scar formation" --- p.26 / Chapter 1.9 --- β-adrenergic receptor (β-AR) --- p.28 / Chapter 1.9.1 --- Functions of β-AR in astrocytes --- p.29 / Chapter 1.10 --- Why do we use C6 glioma cell? --- p.31 / Chapter 1.11 --- Fluorescent differential display (FDD) --- p.34 / Chapter 1.12 --- Aims and Scopes of this project --- p.36 / Chapter Chapter 2 --- MATERIALS AND METHODS / Chapter 2.1 --- Material --- p.40 / Chapter 2.1.1 --- Cell line --- p.40 / Chapter 2.1.2 --- Cell culture reagents --- p.40 / Chapter 2.1.2.1 --- Complete Dulbecco's modified Eagle medium (CDMEM) --- p.40 / Chapter 2.1.2.2 --- Rosewell Park Memorial Institute (RPMI) medium --- p.41 / Chapter 2.1.2.3 --- Phosphate buffered saline (PBS) --- p.41 / Chapter 2.1.3 --- Recombinant cytokines --- p.41 / Chapter 2.1.4 --- Chemicals for signal transduction study --- p.42 / Chapter 2.1.4.1 --- Modulators of p38 mitogen-activated protein kinase (p38 MAPK) --- p.42 / Chapter 2.1.4.2 --- Modulators of protein kinase C (PKC) --- p.42 / Chapter 2.1.4.3 --- Modulators of protein kinase A (PKA) --- p.42 / Chapter 2.1.4.4 --- β-Adrenergic agonist and antagonist --- p.43 / Chapter 2.1.5 --- Antibodies --- p.44 / Chapter 2.1.5.1 --- Anti-p38 mitogen-activated protein kinase (p38 MAPK) antibody --- p.44 / Chapter 2.1.5.2 --- Anti-phosporylation p38 mitogen-activated protein kinase (p-p38 MAPK) antibody --- p.44 / Chapter 2.1.5.3 --- Antibody conjugates --- p.44 / Chapter 2.1.6 --- Reagents for RNA isolation --- p.45 / Chapter 2.1.7 --- Reagents for DNase I treatment --- p.45 / Chapter 2.1.8 --- Reagents for reverse transcription of mRNA and fluorescent PCR amplification --- p.45 / Chapter 2.1.9 --- Reagents for fluorescent differential display --- p.46 / Chapter 2.1.10 --- Materials for excision of differentially expressed cDNA fragments --- p.46 / Chapter 2.1.11 --- Reagents for reamplification of differentially expressed cDNA fragments --- p.46 / Chapter 2.1.12 --- Reagents for subcloning of reamplified cDNA fragments --- p.47 / Chapter 2.1.13 --- Reagents for purification of plasmid DNA from recombinant clones --- p.47 / Chapter 2.1.14 --- Reagents for DNA sequencing of differentially expressed cDNA fragments --- p.47 / Chapter 2.1.15 --- Reagents for reverse transcription-polymerase chain reaction (RT-PCR) --- p.48 / Chapter 2.1.16 --- Reagents for electrophoresis --- p.50 / Chapter 2.1.17 --- Reagents and buffers for Western blot --- p.50 / Chapter 2.1.18 --- Other chemicals and reagents --- p.50 / Chapter 2.2 --- Maintenance of rat C6 glioma cell line --- p.51 / Chapter 2.3 --- RNA isolation --- p.52 / Chapter 2.3.1 --- Measurement of RNA yield --- p.53 / Chapter 2.4 --- DNase I treatment --- p.53 / Chapter 2.5 --- Reverse transcription of mRNA and fluorescent PCR amplification --- p.54 / Chapter 2.6 --- Fluorescent differentia display --- p.55 / Chapter 2.7 --- Excision of differentially expressed cDNA fragments --- p.59 / Chapter 2.8 --- Reamplification of differentially expressed cDNA fragments --- p.59 / Chapter 2.9 --- Subcloning of reamplified cDNA fragments --- p.60 / Chapter 2.10 --- Purification of plasmid DNA from recombinant clones --- p.63 / Chapter 2.11 --- DNA sequencing of differentially expressed cDNA fragments --- p.64 / Chapter 2.12 --- Reverse transcription-polymerase chain reaction (RT-PCR) --- p.66 / Chapter 2.13 --- Western bolt analysis --- p.67 / Chapter Chapter 3 --- RESULTS / Chapter 3.1 --- DNase I treatment --- p.71 / Chapter 3.2 --- FDD RT-PCR and band excision --- p.71 / Chapter 3.3 --- Reamplification of excised cDNA fragments --- p.74 / Chapter 3.4 --- Subcloning of reamplified cDNA fragments --- p.77 / Chapter 3.5 --- DNA sequencing of subcloned cDNA fragments --- p.77 / Chapter 3.6 --- Confirmation of the differentially expressed cDNA fragments by RT-PCR and Western blotting --- p.84 / Chapter 3.6.1 --- Effects of TNF-α on p38a mitogen protein kinase (p38 α MAPK) --- p.84 / Chapter 3.6.2 --- Effects of TNF-α on p38 a MAPK and p-p38 α MAPK protein level --- p.86 / Chapter 3.7 --- Effects of TNF-α on p38 MAPK --- p.88 / Chapter 3.7.1 --- "Effects of TNF-α on p38 α, β,γ andδ MAPK" --- p.88 / Chapter 3.7.2 --- Role of TNF-receptor (TNF-R) subtype in the TNF-α-induced p3 8 MAPK expression in C6 cells --- p.89 / Chapter 3.7.3 --- The signaling system mediating TNF-α-induced p38 a MAPK expression in C6 cells --- p.92 / Chapter 3.7.3.1 --- The involvement of PKC in TNF-α-induced p38 MAPK expression in C6 cells --- p.92 / Chapter 3.7.3.2 --- The involvement of PKC in TNF-α-induced p38 MAPK expression in C6 cells --- p.98 / Chapter 3.7.4 --- The relationship between p38 MAPK and β-adrenergic mechanisms in C6 cells --- p.99 / Chapter 3.7.4.1 --- Effects of isoproterenol and propanol on p38 MAPK mRNA levels in C6 cells --- p.103 / Chapter 3.7.4.2 --- Effects of β1-agonist and -antagonist on p38 MAPK mRNA levels in C6 cells --- p.106 / Chapter 3.7.4.3 --- Effects of β2-agonist and -antagonist on p38 MAPK mRNA levels in C6 cells --- p.107 / Chapter 3.8 --- The relationship between p3 8 MAPK and inducible nitric oxide synthase (iNOS) expression --- p.113 / Chapter 3.8.1 --- Effects of TNF-α on the iNOS expression in C6 cells --- p.113 / Chapter 3.8.2 --- Role of TNF-receptors (TNF-R) subtypes in the TNF-α- induced iNOS expression in C6 cells --- p.115 / Chapter 3.8.3 --- The signaling system mediating TNF-α-induced iNOS expression in C6 cells --- p.115 / Chapter 3.8.3.1 --- The involvement of p38 MAPK in the TNF-α-induced iNOS expression in C6 cells --- p.117 / Chapter 3.8.3.2 --- The involvement of PKA in the TNF-α-induced iNOS expression in C6 cells --- p.119 / Chapter 3.9 --- The relationship between p38 MAPK and cAMP-responsive element binding protein (CREB) expression --- p.120 / Chapter 3.9.1 --- Effects of TNF-α on the CREB expression in C6 cells --- p.120 / Chapter 3.9.2 --- Role of TNF-receptors (TNF-R) subtypes in the TNF-α- induced CREB expression in C6 cells --- p.124 / Chapter 3.9.3 --- The signaling system mediating TNF-α-induced CREB expression in C6 cells --- p.126 / Chapter 3.9.3.1 --- The involvement of p38 MAPK in the TNF-α-induced CREB expression in C6 cells --- p.126 / Chapter 3.9.3.2 --- The involvement of PKC in the TNF-α-induced CREB expression in C6 cells --- p.128 / Chapter 3.9.3.3 --- The involvement of PKA in TNF-α-induced CREB expression in C6 cells --- p.129 / Chapter 3.9.4 --- The relationship between CREB and β-adrenergic mechanisms in C6 cells --- p.136 / Chapter 3.9.4.1 --- Effects of isoproterenol and propanol on CREB mRNA levels in C6 cells --- p.136 / Chapter 3.9.4.2 --- Effects of β1-agonist and -antagonist on CREB mRNA levels in C6 cells --- p.139 / Chapter 3.9.4.3 --- Effects of (32-agonist and -antagonist on CREB mRNA levels in C6 cells --- p.142 / Chapter 3.10 --- The relationship between p38 MAPK and transcription factor c-fos expression --- p.146 / Chapter 3.10.1 --- Effects of TNF-α on the c-fos expression in C6 cells --- p.146 / Chapter 3.10.2 --- Role of TNF-receptors (TNF-R) subtypes in the TNF-α- induced c-fos expression in C6 cells --- p.146 / Chapter 3.10.3 --- The signaling system mediating TNF-α-induced c-fos expression in C6 cells --- p.149 / Chapter 3.10.3.1 --- The involvement of p38 MAPK in the TNF-α-induced c-fos expression in C6 cells --- p.149 / Chapter 3.10.3.2 --- The involvement of PKC in the TNF-α-induced c-fos expression in C6 cells --- p.151 / Chapter 3.10.3.3 --- The involvement of PKA in TNF-α-induced c-fos expression in C6 cells --- p.154 / Chapter 3.10.4 --- The relationship between c-fos and β-adrenergic mechanisms in C6 cells --- p.157 / Chapter 3.10.4.1 --- Effects of isoproterenol and propanolol on c-fos mRNA levels in C6 cells --- p.157 / Chapter 3.10.4.2 --- Effects of β1-agonist and -antagonist on c-fos mRNA levels in C6 cells --- p.160 / Chapter 3.10.4.3 --- Effects of β2-agonist and -antagonist on c-fos mRNA levels in C6 cells --- p.164 / Chapter 3.11 --- The relationship between p38 MAPK and transcription factor NF-kB expression --- p.168 / Chapter 3.11.1 --- Effects of TNF-α on the NF-kB expression in C6 cells --- p.168 / Chapter 3.11.2 --- Role of TNF-receptors (TNF-R) subtypes in the TNF-α- induced NF-kB expression in C6 cells --- p.168 / Chapter 3.11.3 --- The signaling system mediating TNF-α-induced NF-kB expression in C6 cells --- p.171 / Chapter 3.11.3.1 --- The involvement of p38 MAPK in the TNF-α-induced NF-kB expression in C6 cells --- p.171 / Chapter 3.11.3.2 --- The involvement of PKC in the TNF-α-induced NF-kB expression in C6 cells --- p.173 / Chapter Chapter 4 --- DISCUSSION AND CONCLUSION / Chapter 4.1 --- Effects of tumor-necrosis factor-alpha (TNF-α) on C6 cell proliferations --- p.176 / Chapter 4.2 --- The Signaling System Involved in TNF-α-Induced p38 MAPK Expression in C6 cells --- p.178 / Chapter 4.3 --- The Signaling System Involved in TNF-α-Induced iNOS Expression in C6 cells --- p.184 / Chapter 4.4 --- The Signaling System Involved in TNF-α-Induced CREB Expression in C6 cells --- p.186 / Chapter 4.5 --- The Signaling System Involved in TNF-α-Induced c-fos Expressionin in C6 cells --- p.190 / Chapter 4.6 --- The Signaling System Involved in TNF-α-Induced NF-kB Expression in C6 cells --- p.193 / Chapter 4.7 --- Conclusions --- p.195 / Chapter 4.8 --- Possible application / References

by Wong Kin Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 348-373). / Abstracts in English and Chinese. / Abstract --- p.ii / 撮要 --- p.iv / Acknowledgements --- p.vi / Table of Contents --- p.vii / List of Abbreviations --- p.xviii / List of Tables --- p.xxi / List of Figures --- p.xxii / Chapter CHAPTER 1. --- INTRODUCTION / Chapter 1.1. --- Events happened in brain injury --- p.1 / Chapter 1.2. --- An alternate approach based on neuronal regeneration --- p.3 / Chapter 1.3. --- Fate of astrocytes after brain injury --- p.4 / Chapter 1.3.1. --- General information of astrocytes --- p.4 / Chapter 1.3.2. --- Functions of astrocytes --- p.5 / Chapter 1.4. --- Factors relate to astrocytes proliferation --- p.7 / Chapter 1.4.1. --- TNF-α --- p.8 / Chapter 1.4.2. --- β adrenergic mechanism and astrocyte proliferation --- p.11 / Chapter 1.5. --- Cell cycle-related proteins --- p.13 / Chapter 1.5.1. --- Maturation promoting factor (MPF) --- p.15 / Chapter 1.5.2. --- Early G1 phase --- p.16 / Chapter 1.5.3. --- Retinoblastoma protein (pRb) --- p.18 / Chapter 1.5.4. --- Cyclin-dependent kinase (cdk) activating kinase (Cak) --- p.19 / Chapter 1.5.5. --- "Cyclin, cdks, cki" --- p.20 / Chapter 1.5.5.1. --- Cyclins --- p.20 / Chapter 1.5.5.1.1. --- Cyclin D --- p.21 / Chapter 1.5.5.1.2. --- Cyclin E --- p.22 / Chapter 1.5.5.1.3. --- Cyclin A --- p.23 / Chapter 1.5.5.1.4. --- Cyclin B --- p.23 / Chapter 1.5.5.2. --- Cyclin-dependent kinases (cdks) --- p.24 / Chapter 1.5.5.3. --- Cyclin-dependent kinase inhibitor (cki) --- p.24 / Chapter 1.5.5.3.1. --- INK4 proteins (inhibitors of cdk-4 and cdk-6) --- p.25 / Chapter 1.5.5.3.2. --- p21 family proteins --- p.25 / Chapter 1.5.5.3.2.1. --- p21 --- p.25 / Chapter 1.5.5.3.2.2. --- p27 --- p.25 / Chapter 1.6. --- Apoptosis related proteins --- p.26 / Chapter 1.6.1. --- bcl-2 family --- p.26 / Chapter 1.6.1.1. --- bcl-2 --- p.26 / Chapter 1.6.1.2. --- bcl-x --- p.27 / Chapter 1.6.1.3. --- bcl-xα --- p.27 / Chapter 1.6.1.4. --- bcl-w --- p.28 / Chapter 1.6.1.5. --- Myeloid cell leukemia factor 1 (Mcl-1) --- p.28 / Chapter 1.7. --- C6 glioma cell line --- p.28 / Chapter 1.8. --- Aim of this project --- p.30 / Chapter CHAPTER 2. --- MATERIALS & METHODS / Chapter 2.1. --- Materials / Chapter 2.1.1. --- Rat C6 glioma cell line --- p.32 / Chapter 2.1.2. --- Cell culture materials preparation / Chapter 2.1.2.1. --- Complete Dulbecco's Modified Medium (cDMEM) --- p.32 / Chapter 2.1.2.2. --- Serum-free Dulbecco's Modified Medium (sDMEM) --- p.33 / Chapter 2.1.2.3. --- Phosphate buffered saline (PBS) --- p.33 / Chapter 2.1.3. --- Drug preparation / Chapter 2.1.3.1. --- Recombinant cytokines --- p.34 / Chapter 2.1.3.2. --- Antibodies / Chapter 2.1.3.2.1. --- Antibodies used in expression analysis --- p.34 / Chapter 2.1.4. --- Antibodies used in Western blotting --- p.34 / Chapter 2.1.5. --- Reagents for RNA isolation --- p.36 / Chapter 2.1.6. --- Reagents for reverse transcription-polymerase chain reaction (RT-PCR) --- p.36 / Chapter 2.1.7. --- Reagents for Electrophoresis --- p.38 / Chapter 2.1.8. --- Reagents and buffers for Western blotting --- p.38 / Chapter 2.1.9. --- Other chemicals and reagents --- p.39 / Chapter 2.2. --- Methods / Chapter 2.2.1. --- Maintenance of C6 cells --- p.39 / Chapter 2.2.2. --- Preparation of cells for assays --- p.40 / Chapter 2.2.3. --- Drugs preparation --- p.40 / Chapter 2.2.4. --- Determination of RNA expression by RT-PCR analysis / Chapter 2.2.4.1. --- RNA extraction --- p.41 / Chapter 2.2.4.2. --- Spectrophotometric Quantitation of DNA and RNA --- p.43 / Chapter 2.2.4.3. --- RNA gel electrophoresis --- p.43 / Chapter 2.2.4.4. --- Reverse transcription-polymerase chain reaction (RT- PCR) --- p.43 / Chapter 2.2.4.5. --- Separation of PCR products by agarose gel electrophoresis --- p.43 / Chapter 2.2.4.6. --- Quantification of band density --- p.45 / Chapter 2.2.4.7. --- Restriction enzyme (RE) digestion --- p.45 / Chapter 2.2.5. --- Determination of protein expression by Western blotting / Chapter 2.2.5.1. --- Total protein extraction --- p.46 / Chapter 2.2.5.2. --- Western blotting analysis --- p.46 / Chapter CHAPTER 3. --- RESULTS / Chapter 3.1. --- Effects of TNF-α on cell cycle related genes and proteins expression --- p.49 / Chapter 3.1.1. --- Effects of TNF-α on the time courses of cyclin D1 gene and protein expression --- p.49 / Chapter 3.1.2. --- Effect of TNF-α on the time course of cyclin D2 gene expression --- p.50 / Chapter 3.1.3. --- Effects of TNF-α on the time courses of cyclin D3 gene and protein expression --- p.53 / Chapter 3.1.4. --- Effects of TNF-α on the time courses of cdk-4 gene and protein expression --- p.55 / Chapter 3.1.5. --- Effects of TNF-α on the time courses of cyclin E gene and protein expression --- p.55 / Chapter 3.1.6. --- Effects of TNF-α on the time courses of cdk-2 gene and protein expression --- p.58 / Chapter 3.1.7. --- Effects of TNF-α on the time courses of p15 gene and protein expression --- p.61 / Chapter 3.1.8. --- Effects of TNF-α on the time courses of p27 gene and protein expression --- p.61 / Chapter 3.1.9. --- Effects of TNF-α on the time courses of p21 gene and protein expression --- p.64 / Chapter 3.1.10. --- Effects of TNF-α on the time courses of p130 gene and protein expression --- p.66 / Chapter 3.1.11. --- Effects of TNF-α on the time courses of Cak gene and protein expression --- p.66 / Chapter 3.1.12. --- Effects of TNF-α on the time courses of cyclin H gene and protein expression --- p.68 / Chapter 3.1.13. --- Effects of TNF-α on the time courses of cyclin B gene and protein expression- --- p.71 / Chapter 3.1.14. --- Effect of TNF-α on the time course of bcl-2 protein expression --- p.71 / Chapter 3.1.15. --- Effects of TNF-α on the time courses of bcl-XL gene and protein expression --- p.73 / Chapter 3.1.16. --- Effect of TNF-α on the time course of bcl-xα gene expression --- p.73 / Chapter 3.1.17. --- Effects of TNF-α on the time courses of bcl-w gene and protein expression --- p.76 / Chapter 3.1.18. --- Effects of TNF-α on the time courses of Mcl-1 gene expression --- p.76 / Chapter 3.2. --- Effects of TNF-R1 and -R2 on cell cycle related genes and proteins expression --- p.81 / Chapter 3.2.1. --- Effects of blocking TNF-R1/ -R2 on the time courses of cyclin D1 gene and protein expression --- p.81 / Chapter 3.2.2. --- Effect of blocking TNF-R1/ -R2 on the time course of cyclin D2 gene expression --- p.82 / Chapter 3.2.3. --- Effects of blocking TNF-R1/ -R2 on the time courses of cyclin D3 gene and protein expression --- p.85 / Chapter 3.2.4. --- Effects of blocking TNF-R1/ -R2 on the time courses of cdk-4 gene and protein expression --- p.90 / Chapter 3.2.5. --- Effects of blocking TNF-R1/ -R2 on the time courses of cyclin E gene and protein expression --- p.93 / Chapter 3.2.6. --- Effects of blocking TNF-R1/ -R2 on the time courses of cdk-2 gene and protein expression --- p.93 / Chapter 3.2.7. --- Effects of blocking TNF-R1/ -R2 on the time courses of p15 gene and protein expression --- p.96 / Chapter 3.2.8. --- Effects of blocking TNF-R1/ -R2 on the time courses of p27 gene and protein expression --- p.99 / Chapter 3.2.9. --- Effects of blocking TNF-R1/ -R2 on the time courses of p21 gene and protein expression --- p.103 / Chapter 3.2.10. --- Effects of blocking TNF-R1/ -R2 on the time courses of pl30 gene and protein expression --- p.106 / Chapter 3.2.11. --- Effect of blocking TNF-R1/ -R2 on the time course of Cak gene expression --- p.110 / Chapter 3.2.12. --- Effects of blocking TNP-R1/ -R2 on the time courses of cyclin H gene and protein expression --- p.110 / Chapter 3.2.13. --- Effects of blocking TNF-R1/ -R2 on the time courses of cyclin B gene and protein expression --- p.112 / Chapter 3.2.14. --- Effect of blocking TNF-R1/ -R2 on the time course of bcl-2 protein expression --- p.116 / Chapter 3.2.15. --- Effects of blocking TNF-R1/ -R2 on the time courses of bcl-xL gene and protein expression --- p.119 / Chapter 3.2.16. --- Effect of blocking TNF-R1/ -R2 on the time course of bcl-xα gene expression --- p.122 / Chapter 3.2.17. --- Effects of blocking TNF-R1/ -R2 on the time courses of bcl-w gene and protein expression --- p.124 / Chapter 3.2.18. --- Effect of blocking TNF-R1/ -R2 on the time course of Mcl-1 gene expression --- p.124 / Chapter 3.3. --- "Effects of other cytokines (IL-6, IL-lα, IL-lβ, IFγ) on cell cycle related genes and proteins expression" --- p.129 / Chapter 3.3.1. --- "Effects of TNF-α, IL-6, IL-lα, IL-lβ, IFγ on cyclin D1 gene and protein expression" --- p.129 / Chapter 3.3.2. --- "Effects of TNF-a, IL-6, IL-lα, IL-lβ, IFγ on cyclin D2 gene and protein expression" --- p.132 / Chapter 3.3.3. --- "Effects of TNF-α, IL-6, IL-lα, IL-1β, IFγ on cyclin D3 gene and protein expression" --- p.136 / Chapter 3.3.4. --- "Effects of TNF-α, IL-6, IL-lα, IL-1β, IFγ on cdk-4 gene and protein expression" --- p.140 / Chapter 3.3.5. --- "Effects of TNF-α, IL-6, IL-lα, IL-1β, IFγ on cyclin E gene and protein expression" --- p.144 / Chapter 3.3.6. --- "Effects of TNF-α, IL-6, IL-lα, IL-1β, IFγ on cdk-2 gene and protein expression" --- p.148 / Chapter 3.3.7. --- "Effects of TNF-α, IL-6, IL-lα, IL-1β, IFγ on pl5 gene and protein expression" --- p.152 / Chapter 3.3.8. --- "Effects of TNF-α, IL-6, IL-lα, IL-1β, IFγ on p27 gene and protein expression" --- p.152 / Chapter 3.3.9. --- "Effects of TNF-α, IL-6, IL-lα, IL-ip, IFγ on p21 gene and protein expression" --- p.159 / Chapter 3.3.10. --- "Effects of TNF-α, IL-6, IL-lα, IL-lβ, IFγ on pl30 gene and protein expression" --- p.162 / Chapter 3.3.11. --- "Effects of TNF-α, IL-6, IL-lα, IL-lp, IFγ on Cak gene expression" --- p.166 / Chapter 3.3.12. --- "Effects of TNF-α, IL-6, IL-lα, IL-1β, IFy on cyclin H gene and protein expression -" --- p.170 / Chapter 3.3.13. --- "Effects of TNF-α, IL-6, IL-lα, IL-1β, IFγ on cyclin B gene and protein expression" --- p.174 / Chapter 3.3.14. --- "Effects of TNF-α, IL-6, IL-lα, IL-1β, IFγ on bcl-2 gene and protein expression" --- p.178 / Chapter 3.3.15. --- "Effects of TNF-a, IL-6, IL-lα, IL-1β, IFγ on bcl-xL gene and protein expression" --- p.178 / Chapter 3.3.16. --- "Effects of TNF-α, IL-6, IL-lα, IL-1β, IFγ on bcl-xα gene expression" --- p.184 / Chapter 3.3.17. --- "Effects of TNF-α, IL-6, IL-lα, IL-lβ, IFγ on bcl-w gene and protein expression" --- p.187 / Chapter 3.3.18. --- "Effects of TNF-α, IL-6, IL-lα, IL-1β, IFγ on Mcl-1 gene expression" --- p.191 / Chapter 3.4. --- Effects of P-ARs on cell cycle related genes expression --- p.194 / Chapter 3.4.1. --- Effects of β-AR agonists and antagonists on cyclin D1 gene expression --- p.195 / Chapter 3.4.2. --- Effects of β-AR agonists and antagonists on cyclin D2 gene expression --- p.198 / Chapter 3.4.3. --- Effects of β-AR agonists and antagonists on cyclin D3 gene expression --- p.201 / Chapter 3.4.4. --- Effects of β-AR agonists and antagonists on cdk-4 gene expression --- p.204 / Chapter 3.4.5. --- Effects of β-AR agonists and antagonists on cyclin E gene expression --- p.207 / Chapter 3.4.6. --- Effects of β-AR agonists and antagonists on cdk-2 gene expression - --- p.210 / Chapter 3.4.7. --- Effects of β-AR agonists and antagonists on p15 gene expression --- p.213 / Chapter 3.4.8. --- Effects of β-AR agonists and antagonists on p27 gene expression --- p.216 / Chapter 3.4.9. --- Effects of β-AR agonists and antagonists on p21 gene expression --- p.219 / Chapter 3.4.10. --- Effects of β-AR agonists and antagonists on p130 gene expression --- p.222 / Chapter 3.4.11. --- Effects of β-AR agonists and antagonists on Cak gene expression --- p.225 / Chapter 3.4.12. --- Effects of β-AR agonists and antagonists on cyclin H gene expression --- p.228 / Chapter 3.4.13. --- Effects of β-AR agonists and antagonists on cyclin B gene expression --- p.231 / Chapter 3.4.14. --- Effects of β-AR agonists and antagonists on bcl-XL gene expression --- p.233 / Chapter 3.4.15. --- Effects of β-AR agonists and antagonists on bcl-xα gene expression --- p.236 / Chapter 3.4.16. --- Effects of β-AR agonists and antagonists on bcl-w gene expression --- p.239 / Chapter 3.4.17. --- Effects of β-AR agonists and antagonists on Mcl-1 gene expression --- p.243 / Chapter CHAPTER 4. --- DISCUSSION & CONCLUSION --- p.247 / Chapter 4.1. --- Effects of TNF-α on the induction of cell cycle regulatory genes/proteins expression --- p.248 / Chapter 4.2. --- Effects of TNF-α on bcl-2 family apoptotic inhibitor genes expression --- p.250 / Chapter 4.3. --- The TNF-R subtype(s) responsible for the TNF-a-induced cell cycle regulatory genes and proteins expression --- p.251 / Chapter 4.4. --- Is the TNF-α-induced cell cycle regulatory genes and proteins expression cytokine specific? --- p.253 / Chapter 4.5. --- The relationship between TNF-α and β-adrenergic mechanism in C6 cell proliferation --- p.254 / Chapter 4.6. --- General Discussion --- p.256 / Chapter 4.7. --- Possible treatments for brain injury --- p.258 / APPENDIX --- p.259 / REFERENCES --- p.348