Traumatic brain injuries (TBIs) are injuries to the brain associated with the transfer of energy from some external source. There are an estimated 1.4 million TBIs each year, and about half are due to transportation crashes (NINDS, 2007). Driver distraction is defined as a process or condition that draws a driver's attention away from driving activities toward a competing activity (Sheridan, 2004) and has been identified as an under-examined issue for TBI populations (Cyr, et al., 2008). The interaction between the cognitive impairments related to TBIs and the competing demands from driver distraction may be especially problematic. The goal of this dissertation is to investigate the effect of driver distraction on individuals with TBI. This dissertation uses several approaches and data sources: crash data, a TBI registry, a survey of TBI drivers, and an on-road driving study of TBI and non-TBI drivers. Results demonstrate that a subset of TBI drivers are more willing to engage in distracting tasks and they are more likely to have received speeding tickets. TBI drivers involved in crashes were less likely to wear seatbelts and were more likely to be involved in multiple crashes compared to all other drivers in crashes. Additionally, a subset of TBI drivers exhibits more risk-taking while driving that may result from the TBI or a predisposition to take risks. A Bayesian approach was used to analyze the effect of distracting tasks on driving performance of TBI drivers in an on-road study. A simulator study of non-TBI drivers was used to develop prior distributions of parameter estimates. The distracting tasks include a CD selecting task, a coin sorting task, and a radio tuning task. All of the tasks contained visual-manual components and the coin sorting task contained an additional cognitive component associated with counting the currency. This suggests that TBI drivers exhibited worse driving performance during a coin sorting task than the non-TBI drivers in terms of the standard deviation of speed and maximum lateral acceleration of the vehicle. This suggests that the cognitive component of the coin sorting task may be causing the decreased performance for the TBI drivers. Across all tasks, TBI drivers spent a larger percent of the task duration looking at the task with a larger number of glances towards the distraction task than the non-TBI drivers. Driver distractions with cognitive components may be especially problematic for TBI drivers. Future work should investigate if this effect is consistent across more complex cognitive driver distraction tasks (e.g., cell phone usage) for this population. Additionally, future work should validate the high proportion of TBI drivers involved in multiple crashes.

Objective: To identify disruption due to dizziness symptoms following deployment-related traumatic brain injury (TBI) and factors associated with receiving diagnoses for these symptoms. Setting: Administrative medical record data from the Department of Veterans Affairs (VA). Participants: Post-9/11 veterans with at least 3 years of VA care who reported at least occasional disruption due to dizziness symptoms on the comprehensive TBI evaluation. Design: A cross-sectional, retrospective, observational study. Main Measures: International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes of dizziness, vestibular dysfunction, and other postconcussive conditions; neurobehavioral Symptom Inventory. Results: Increased access to or utilization of specialty care at the VA was significant predictors of dizziness and/or vestibular dysfunction diagnoses in the fully adjusted model. Veterans who identified as Black non-Hispanic and those with substance use disorder diagnoses or care were substantially less likely to receive dizziness and vestibular dysfunction diagnoses. Conclusions: Access to specialty care was the single best predictor of dizziness and vestibular dysfunction diagnoses, underscoring the importance of facilitating referrals to and utilization of specialized, comprehensive clinical facilities or experts for veterans who report disruptive dizziness following deployment-related TBI. There is a clear need for an evidence-based pathway to address disruptive symptoms of dizziness, given the substantial variation in audiovestibular tests utilized by US providers by region and clinical specialty. Further, the dearth of diagnoses among Black veterans and those in more rural areas underscores the potential for enhanced cultural competency among providers, telemedicine, and patient education to bridge existing gaps in the care of dizziness.

Excerpt: With all that is currently known about symptoms that indicate mild traumatic brain injury (MTBI), it is unfortunate that many individuals go undiagnosed for long periods of time after sustaining such an injury.

No description available.

Health professionals as well as families are being confronted with long-term care and caregiver issues that accompany the increasing incidence of individuals surviving traumatic brain injury. A sample of parents and brain-injured offspring from 20 families served as informants. The purpose of this study was to identify a qualitatively generated theory describing the parent's experience following a brain-injured child's return to the home setting. An exploratory qualitative design using grounded theory methodology was used during data collection and analysis. All the brain-injured offspring had survived a moderate-to-severe traumatic brain injury; were living with at least one parent; and were ages 17 to 34. A three-phase theory, Investing in the Comeback, was generated using grounded theory methodology. The theory's three stages, centering on fostering independence and seeking stability, describe the work of the parent living with a brain-injured offspring. The first phase, Centering On, involves the parent's focusing attention and behavior primarily on the brain-injured offspring. During Fostering Independence, the second phase, the parent initiates and maintains efforts to promote the offspring's resumption of independent functioning. The final phase, Seeking Stability, consists of the parent working to establish a regime that maintains the brain-injured offspring's optimal performance, while minimizing the strain on other family members. Theoretical sampling guided the identification of categories, properties, conditions, and consequences of each phase. Four quantitative measures supplied descriptions of sample characteristics and included demographics, cognitive deficit ratings of the child by the parent and the investigator, and the parent's perception of the family's functioning.

Bakgrund: Kunskapen om barnmisshandel hos vårdpersonal har börjat kritiseras i Sverige. Röntgensjuksköterskan är skyldig att rapportera vid misstänkt barnmisshandel och behöver därför kunna identifiera dessa fall. Syfte: Syftet var att beskriva radiologiska fynd som kan indikera barnmisshandel. Metod: Studierna i denna litteraturstudie kvalitetsgranskades, analyserades och bearbetades för att sammanställa ett resultat. Tio kvantitativa studier ingick i resultatet för litteraturstudien. PubMed och CINAHL användes som sökdatabaser. Resultat: Resultatet presenterades i tre kategorier: hjärnskador och blödningar, frakturer och ligamentskador. Konklusion: Vanliga radiologiska fynd som kan indikera barnmisshandel är subduralblödningar, revbensfrakturer och rörbensfrakturer. Vidare forskning bör utföras för att undersöka prevalensen av frakturer i händer och fötter samt ligamentskador i halsryggen vid misstänkt barnmisshandel. / Background: Swedish health care professionals’ knowledge about child abuse has lately been criticized. The radiographer is obligated to report on suspected child abuse and therefore needs to be able to identify these cases. Aim: The aim was to describe radiological findings that might indicate child abuse. Method: The studies in this literature review were quality assessed, analyzed and processed to compile the results. The results consisted of ten quantitative studies. PubMed and CINAHL were used as search databases. Results: The results were presented in three categories: brain injuries and hemorrhages, fractures and ligamentous injuries. Conclusion: Common radiological findings that might indicate child abuse are subdural hemorrhages, rib fractures and long bone fractures. Continued research should be conducted to investigate the prevalence of fractures in hands and feet, and also ligamentous injuries of the cervical spine in suspected child abuse.

INTRODUÇÃO: O Traumatismo Cranioencefálico (TCE) é uma das maiores causas de mortalidade e incapacidade em adultos em todo o mundo. Uma complicação frequente e precoce do TCE é o desenvolvimento de hipertensão intracraniana, cujo diagnóstico e tratamento intensivo geralmente requer monitorização invasiva da pressão intracraniana (PIC); o interesse científico neste campo é crescente. Neste contexto, estudos recentes têm demonstrado que é possível detectar hipertensão intracraniana de forma não-invasiva através da aferição ultrassonográfica do diâmetro da bainha do nervo óptico (BNO), utilizando-se ultrassonografia do nervo óptico (USNO) com insonação pela janela transorbitária. Não se sabe ainda, entretanto, se essa aferição do diâmetro da BNO por USNO tem um real significado prognóstico quando aplicada em pacientes na fase aguda de um TCE. Neste estudo, objetiva-se avaliar o valor prognóstico da aferição do diâmetro da BNO por USNO, avaliada na admissão, em pacientes vítimas de TCE moderado e grave. MÉTODOS: Avaliaramse prospectivamente pacientes vítimas de TCE moderado ou grave (pontuação < 15 na escala de coma de Glasgow [GCS] ou com lesão intracraniana aguda na tomografia de crânio) admitidos na Unidade de Emergência do HCFMRP-USP, com idades entre 18 e 80 anos, de fevereiro/2015 a julho/2015. Após consentimento livre e esclarecido, estes pacientes foram submetidos a avaliação clínica com escalas padronizadas (NOS-TBI), e radiológica (incluindo tomografia de crânio e USNO) e seguidos até sua alta para avaliação cega do seu desfecho funcional (avaliada pela escala modificada de Rankin [mRS]). Após análise univariada, utilizou-se regressão linear e regressão logística multivariada, para identificação de preditores independentes do déficit neurológico (NOS-TBI) e da incapacidade funcional na alta (mRS). Aplicou-se, ainda, curva ROC e estatística C para avaliar a acurácia da USNO em relação incapacidade grave ou óbito intra-hospitalar. RESULTADOS: 70 pacientes foram analisados, sendo 63 (90%) homens, idade média 37,5 ± 15,1 anos, sendo 32 (45%) pacientes com TCE grave e 29 (41%) causados por acidentes de trânsito. Na análise multivariada por regressão linear, o diâmetro médio da BNO (B=4,8; IC 95%: 0,51 a 9,1; p=0,029) e a gravidade do comprometimento do nível de consciência (GCS) na admissão (B=-1,97; IC 95%: -2,9 a -1,0; p<0,001) foram os únicos preditores independentes da severidade do déficit neurológico na alta pela escala NOS-TBI. Na regressão logística multivariada, o diâmetro médio da BNO (OR:2,1; IC 95%:1,1 a 3,9; p=0,021) foi independentemente associado com um escore de mRS>=4 à alta, mesmo após ajuste para idade e GCS na admissão. CONCLUSÕES: Uma maior distensão da bainha do nervo óptico nas primeiras 24 após TCE moderado a grave está independentemente associada a pior déficit neurológico e capacidade funcional à alta. Esses resultados sugerem que a USNO deve ser mais explorada como método com potencial para orientar medidas terapêuticas intensivas de neuroproteção e controle de hipertensão intracraniana na fase aguda do TCE. / BACKGROUND: Traumatic brain injury (TBI) is a major cause of mortality and disability among adults worldwide. Intracranial hypertension is a frequent and early complication in such patients and its diagnosis and intensive management often require invasive monitoring of intracranial pressure (ICP). In this context, recent studies have shown that it is possible to non-invasively detect intracranial hypertension by ultrasound measurement of optic nerve sheath diameter (ONSD), using optic nerve ultrasound (ONUS) with trans-orbital window insonation. It is still unclear, however, whether the ONSD measurement through ONUS has real prognostic significance when applied to patients in the acute phase of a TBI. In this study, we aimed to evaluate the prognostic value of ONSD measurement by ONUS at admission in patients with moderate and severe TBI. METHODS: We prospectively evaluated patients with moderate or severe TBI (score <15 Glasgow Coma Scale [GCS] or acute intracranial lesion on CT scan) admitted to the Emergency Unit of HCFMRP- USP, aged 18 to 80 years, from February / 2015 to July / 2015. After informed consent, these patients underwent clinical evaluation with standardized scales (NOS-TBI), and radiological (including CT scan and ONUS), and blinded functional outcome assessment at discharge (assed by modified Rankin Scale - mRS). After univariate analysis, we used linear regression and multivariate logistic regression to identify independent predictors of neurological deficit at discharge (NOS-TBI and mRS). We also used ROC Curves and C statistics to evaluate the accuracy of different ONSD cut-offs to identify severe disability and death at discharge. RESULTS: We analyzed 70 patients, 63 (90%) men, mean age 37.5 ± 15.1 years, 32 (45%) with severe TBI, 29 (41%) caused by traffic accidents. After multivariate linear regression analysis, the average diameter of the ONSD (B=4.8; IC 95%: 0.51 a 9.1; p=0.029) and the severity of consciousness impairment (GCS) at admission (B=-1,97; IC 95%: -2,9 a -1,0; p<0,001) were the only independent predictors of neurological deficit severity by the NOS-TBI scale at discharge. On multivariate logistic regression analysis, after age and GCS adjust, the mean ONSD was independently associated with a mRS>=4 at discharge. CONCLUSIONS: Increased distension of the optic nerve sheath in the first 24 after a moderate to severe TBI is independently associated with a worse neurological and functional outcome at discharge. Our results indicate that additional studies should be performed to test ONUS as a method with potential to guide intensive therapeutic measures of neuroprotection and intracranial hypertension control in the acute phase after TBI.

Introdução: O traumatismo cranioencefálico (TCE) caracteriza-se por ser uma lesão não degenerativa e não congênita e que é provocado por uma força mecânica externa. Espera-se um prejuízo, permanente ou temporário, nas funções cognitiva, física e psicossocial, com diminuição ou alteração do estado de consciência. As consequências residuais pós-TCE acometem de forma diferente cada paciente. A maioria das pessoas que sofrem traumas leves tem um processo de recuperação sem grandes complicações, e são capazes de retornar às suas atividades pré-trauma. Entretanto, a maioria dos pacientes que sofrem de TCE moderado e grave apresentam sequelas e limitações. Uma das opções medicamentosas vigentes e descritas em relatos de casos são os inibidores de acetilcolinesterase que mostram benefícios significativos quanto a melhora atencional e principalmente da memória quando utilizados em paciente na fase crônica pós TCE. Objetivo: Investigar a eficácia da rivastigmina em pacientes com comprometimento cognitivo crônico após o TCE. Métodos: Foi realizado um estudo duplo-cego, controlado com placebo em pacientes com TCE. Catorze pacientes com TCE (sete que tomaram o remédio ativo e sete que tomaram placebo) entre 18 e 70 anos completaram o estudo. Os pacientes foram randomizados em dois grupos, para receber rivastgmina ou placebo. Utilizou-se para análise dos dados comparativos entre grupo medicamento e placebo, análise estatística Z escore, teste T, qui-quadrado, correlação com o EEG e teste de correlação. Resultados: Observou-se que os pacientes que receberam a rivastigmina apresentaram melhora nos testes Cubos, BAI e memória visual de evocação imediata. No entanto, estas diferenças não foram estatisticamente significativas pelos padrões usualmente utilizados em trabalhos da área médica (alfa de 5%). Conclusão: Os resultados obtidos em pacientes com TCE apontam uma tendência que o tratamento medicamentoso com rivastigmina (medicação anti-colinesterásica) pode favorecer a estabilização ou resultar até mesmo em melhora dos déficits cognitivos, emocionais e funcionais. São necessários mais estudos com número maior de pacientes para aprofundarmos os achados aqui encontrados / Introduction: Traumatic brain injury (TBI) is characterized by a nondegenerative and non-congenital injury and is caused by an external mechanical force. Permanent or temporary impairment is expected in cognitive, physical and psychosocial functions, with a decrease or alteration of the state of consciousness. The residual consequences after TBI affect each patient differently. Most people who suffer mild trauma have a recovery process without major complications and are able to return to their pre-trauma activities. However, most patients suffering from moderate and severe TBI have sequelae and limitations. One of the current and described drug options in case reports are acetylcholinesterase inhibitors that show significant benefits in terms of attentional and especially memory improvement when used in patients in the chronic phase after TBI. Objective: To investigate the efficacy of rivastigmine in patients with chronic cognitive impairment after TBI. Methods: A double-blind, placebo-controlled study was performed in patients with TBI. Fourteen patients with TBI (seven who took the active drug and seven who took placebo) between 18 and 70 years completed the study. Patients were randomized into two groups to receive rivastgmin or placebo. To analyze the comparative data between drug group and placebo, statistical analysis Z score, T test, chi-square, correlation with the EEG and correlation test were used. Results: It was observed that the patients who received rivastigmine presented improvement in the Cubus, BAI and visual memory of immediate recall. However, these differences were not statistically significant by the standards commonly used in medical papers (5% alpha). Conclusion: The results obtained in patients with TBI point to a tendency that drug therapy with rivastigmine (anti-cholinesterase medication) may favor stabilization or even result in improvement of cognitive, emotional and functional deficits. Further studies with a larger number of patients are needed to deepen the findings found here

INTRODUÇÃO: Estudos indicam que a morte encefálica está associada com alterações hemodinâmicas, hormonais e inflamatórias, comprometendo a viabilidade dos órgãos para o transplante. Porém, é necessário esclarecer quais destas alterações são decorrentes da morte encefálica e quais são devidas ao trauma associado. Este estudo tem por objetivo avaliar a microcirculação mesentérica, quantificar marcadores sistêmicos da resposta inflamatória, e analisar as alterações histopatológicas em ratos submetidos à morte encefálica comparados com ratos falso-operados. MÉTODOS: Ratos Wistar machos (300 50 g), anestesiados com isoflurano (5-2 %), foram intubados e mecanicamente ventilados (10 mL/kg, 70 ciclos/min). Através de uma trepanação, um cateter Fogarty® 4 F foi inserido no espaço intracraniano e rapidamente insuflado com 500 L de água para indução da morte encefálica. Após a indução da morte encefálica o anestésico foi retirado e os animais receberam solução salina 0,9 % endovenosa (2 mL/h). Animais falso-operados foram apenas trepanados. Pressão arterial média e frequência cardíaca foram monitoradas ao longo de todo tempo de experimento. Após 30, 180 ou 360 min, foram avaliados os seguintes parâmetros: 1) avaliação da perfusão e interação leucócito-endotélio na microcirculação mesentérica por técnica de microscopia intravital; 2) expressão de moléculas de adesão endoteliais (P-selectina e ICAM-1) por imunohistoquímica; 3) quantificação das citocinas (TNF-?, IL-1?, IL-6, e IL-10), quimiocinas (CINC-1 e CINC-2) e corticosterona séricas; 4) determinação do leucograma, hematócrito e gasometria; 5) avaliação histológica do coração, pulmão, fígado e rim. RESULTADOS: A morte encefálica resultou em imediato pico hipertensivo seguido de episódio de hipotensão, associado com queda na perfusão mesentérica para aproximadamente 30% de microvasos com fluxo sanguíneo normal (p<0,0001). A interação dos leucócitos com o endotélio apresentou um menor número de leucócitos rollers (p<0,0001), com maior migração leucocitária (p=0,03) para o tecido perivascular de ratos com morte encefálica, decorridos 180 min de experimento. A expressão de P-selectina não diferiu entre os grupos, enquanto que ICAM-1 teve sua expressão aumentada na terceira hora após a indução da morte encefálica (p<0,01). As concentrações séricas de citocinas e quimiocinas foram iguais entre animais com morte encefálica e falso-operados. Observou- se queda acentuada nos níveis séricos de corticosterona de animais com morte encefálica após 3 h de experimento (p<0,0001). O número de leucócitos totais nos animais com morte encefálica foi menor quando comparado com animais falso-operados (p<0,05), sendo observado aumento na razão neutrófilo/linfócito, após 3h de experimento, em ambos os grupos. Não foram observadas alterações significativas nos dados gasométricos e hematócrito. A morte encefálica induziu alterações histopatológicas nos quatro órgãos avaliados, sendo observada congestão vascular no coração (p=0,02) e pulmão (p=0,02), edema alveolar pulmonar (p=0,001), infiltrado leucocitário no fígado (p=0,01), e edema tubular renal (p=0,04). CONCLUSÕES: A morte encefálica desencadeou instabilidade hemodinâmica associada com hipoperfusão tecidual, além de queda na concentração de corticosterona endógena, resultando em aumento da expressão de ICAM-1 com maior migração de leucócitos na microcirculação mesentérica, além de leucopenia. Os órgãos sólidos apresentaram maior congestão vascular, sendo que os pulmões foram os órgãos mais comprometidos / BACKGROUND: Studies indicate that brain death is associated with hemodynamic, hormonal and inflammatory alterations, compromising the viability of organs to transplantation. However, it is necessary to clarify which of these alterations are consequences of brain death and which are due to brain death-associated trauma. This study aims to evaluate the mesenteric microcirculation, quantify systemic markers of the inflammatory response, and analyze the histopathological changes in rats submitted to brain death compared with sham operated animals. METHODS: Male Wistar rats (300 50 g) anesthetized with isoflurane (5-2 %) were intubated and mechanically ventilated (10 mL/kg, 70 breaths/min). Through trepanation, a Fogarty 4 F catheter was inserted intracranially and quickly inflated with 500 L of water to induce brain death. After brain death confirmation, anesthesia was stopped and the animals received 0.9 % saline solution intravenously (2 mL/h). Sham operated animals were just trepanned. Mean arterial blood pressure and heart rate were continuously monitored. After 30, 180 or 360 min, the following parameters were evaluated: 1) perfusion of microvessels and leukocyte- endothelial interactions in the mesenteric microcirculation by intravital microscopy; 2) expression of endothelial adhesion molecules (P-selectin and ICAM-1) by immunohistochemistry; 3) quantification of serum cytokines (TNF-?, IL-1?, IL-6 and IL-10), chemokines (CINC-1 and CINC-2), and corticosterone; 4) determination of white blood cell counts, hematocrit, and blood gases; 5) histological assessment of heart, lung, liver, and kidney. RESULTS: Brain death induced an immediate hypertensive peak followed by hypotension associated with a reduction in mesenteric perfusion to 30% of microvessels with normal blood flow (p<0.0001). Number of rolling leukocytes was reduced (p<0.0001), and migrated leukocytes to perivascular tissue increased after 180 min (p=0.03). The expression of P-selectin did not differ between groups, whereas the expression of ICAM-1 was increased 3 h after brain death induction (p<0.01). Increased serum concentrations of cytokines and chemokines were observed in both brain death and sham operated rats. Brain death rats showed a decrease in serum corticosterone levels after 3 h (p<0.0001). Total white blood cell counts in brain death rats was reduced when compared with sham operated rats (p<0.05), associated with an increase in neutrophil/lymphocyte ratio after 3 h in both groups. No significant changes in hematocrit and blood gases were observed. Brain death induced histopathological alterations in the evaluated organs: vascular congestion in the heart and lungs (p=0.02), pulmonary alveolar edema (p=0.001), leukocyte infiltration in the liver (p=0.01), and renal tubular edema (p=0.04). CONCLUSIONS: Brain death triggered hemodynamic instability associated with tissue hypoperfusion, and a decrease in the concentration of endogenous corticosterone, resulting in increased expression of ICAM-1 with increased migration of leukocytes at mesenteric microcirculation, associated with a paradoxical leukopenia. The main histopathological alteration in brain death rats was vascular congestion, and the lungs are the most compromised organs

Wong Chun Lung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 202-225). / Abstracts in English and Chinese. / Thesis Committee --- p.ii / Abstract --- p.iii / 摘要 --- p.vi / Acknowledgements --- p.ix / Table of Contents --- p.x / List of Abbreviations --- p.xv / List of Figures --- p.xix / List of Tables --- p.xx iii / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- "Neurodegeneration, Inflammation and Gliosis" --- p.1 / Chapter 1.2 --- Anatomy of the CNS --- p.5 / Chapter 1.3 --- Astrocytes --- p.6 / Chapter 1.3.1 --- Morphology and Identification of Astrocytes --- p.6 / Chapter 1.3.2 --- Physiological Functions of Astrocytes in the CNS --- p.7 / Chapter 1.3.2.1 --- Induction of Blood-brain Barrier (BBB) --- p.7 / Chapter 1.3.2.2 --- Metabolism of Neurotransmitters --- p.9 / Chapter 1.3.2.3 --- Nursing Role of Astrocytes --- p.9 / Chapter 1.3.2.4 --- Immunological Functions of Astrocytes --- p.10 / Chapter 1.3.3 --- Neonatal Rat Cortical Astrocytes as In Vitro Model --- p.12 / Chapter 1.4 --- Cytokines in Brain Damage --- p.14 / Chapter 1.4.1 --- Lipopolysaccharides (LPS) --- p.16 / Chapter 1.4.2 --- Tumor Necrosis Factor-α (TNF-α) --- p.17 / Chapter 1.4.3 --- Interleukin-1 (IL-1) --- p.19 / Chapter 1.4.4 --- Interleukin-6 (IL-6) --- p.20 / Chapter 1.4.5 --- Interferon-γ (IFN-γ) --- p.21 / Chapter 1.5 --- Cytokines-induced Signaling Cascade --- p.22 / Chapter 1.5.1 --- TNF Receptors --- p.23 / Chapter 1.5.2 --- Ca2+ --- p.25 / Chapter 1.5.3 --- MAPK --- p.26 / Chapter 1.5.4 --- PICA --- p.27 / Chapter 1.5.5 --- NFkB --- p.29 / Chapter 1.6 --- Glucose Metabolism in the Brain and Glucose Transporters --- p.31 / Chapter 1.6.1 --- Glucose Transporters in the Brain --- p.32 / Chapter 1.6.2 --- Glucose Transporters in Brain Damage --- p.34 / Chapter 1.7 --- Ascorbic Acid Metabolism in the Brain --- p.36 / Chapter 1.8 --- Aim and Scope of this Project --- p.39 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1 --- Materials / Chapter 2.1.1 --- Neonatal Sprawley 一Dawley Rats --- p.43 / Chapter 2.1.2 --- Plain Dulbecco Modified Eagle Medium ´ؤ Formula 12 (pDF12) --- p.43 / Chapter 2.1.3 --- Complete DF-12(cDF12) --- p.43 / Chapter 2.1.4 --- Phosphate Buffered Saline (PBS) --- p.44 / Chapter 2.1.5 --- Hank's Buffer (HSB) --- p.44 / Chapter 2.1.6 --- D/L-Homocysteine Buffer --- p.44 / Chapter 2.1.7 --- "LPS, Cytokines and Pentoxifylline" --- p.45 / Chapter 2.1.8 --- Specific TNF Receptor Agonist: TNF antibodies --- p.45 / Chapter 2.1.9 --- Calcium Modulators --- p.45 / Chapter 2.1.10 --- PKA Modulators --- p.46 / Chapter 2.1.11 --- NFkB Inhibitors --- p.47 / Chapter 2.1.12 --- MAPK Inhibitors --- p.47 / Chapter 2.1.13 --- β-Adrenergic Receptor Modulators --- p.47 / Chapter 2.1.14 --- Reagents for RNA and Protein Isolation --- p.48 / Chapter 2.1.15 --- Reagents for Reverse Transcription-Polymerase Chain Reaction (RT-PCR) --- p.48 / Chapter 2.1.16 --- Reagents for DNA Electrophoresis --- p.49 / Chapter 2.1.17 --- Reagents for Real-time PCR --- p.51 / Chapter 2.1.18 --- Reagents for Western Blotting --- p.51 / Chapter 2.1.19 --- Reagents for MTT Assay --- p.51 / Chapter 2.1.20 --- Reagents for 3H-Thymidine Incorporation Assay --- p.52 / Chapter 2.1.21 --- Reagents for Glucose Uptake Assay --- p.52 / Chapter 2.1.22 --- Reagents for Ascorbic Acid Accumulation Assay --- p.53 / Chapter 2.1.23 --- Reagents for Immunostammg --- p.53 / Chapter 2.1.24 --- Other Chemicals and Reagents --- p.53 / Chapter 2.2 --- Methods / Chapter 2.2.1 --- Preparation of Primary Cultured Rat Astrocytes --- p.55 / Chapter 2.2.2 --- Measuring Cell Viability: MTT Assay --- p.56 / Chapter 2.2.3 --- Measuring Cell Proliferation: 3H Thymidine Incorporation Assay --- p.57 / Chapter 2.2.4 --- Measuring Glucose Uptake: Zero-trans Glucose Uptake Assay --- p.58 / Chapter 2.2.5 --- Measuring Ascorbic Acid Accumulation --- p.60 / Chapter 2.2.6 --- Total Protein Extraction --- p.61 / Chapter 2.2.7 --- Western Blotting --- p.62 / Chapter 2.2.8 --- Immunostaining --- p.64 / Chapter 2.2.9 --- Isolation of RNA --- p.64 / Chapter 2.2.10 --- Measurement of RNA Yield --- p.65 / Chapter 2.2.11 --- RNA Gel Electrophoresis --- p.66 / Chapter 2.2.12 --- Reverse Transcription (RT) --- p.66 / Chapter 2.2.13 --- Polymerase Chain Reaction (PCR) --- p.67 / Chapter 2.2.14 --- Separation of PCR Products by Agarose Gel Electrophoresis --- p.67 / Chapter 2.2.15 --- Quantization of PCR Products and Western Blotting --- p.68 / Chapter 2.2.16 --- Real-time PCR --- p.68 / Chapter Chapter 3 --- Results / Chapter 3.1 --- Role of Calcium Ions (Ca2+) in TNF-α-induced Astrocyte Proliferation --- p.70 / Chapter 3.1.1 --- Effects of Changes of Extracellular Ca2+ on Astrocyte Viability --- p.72 / Chapter 3.1.2 --- Effects of Other Divalent Ions on Astrocyte Viability --- p.74 / Chapter 3.1.3 --- Effects of Changes of Intracellular Ca2+ on Astrocyte Viability --- p.78 / Chapter 3.1.4 --- Role of Ca2+ on TNF-α-mduced Proliferation in Astrocytes --- p.85 / Chapter 3.1.5 --- Role of Other Divalent Ions on tnf-α-mduced Proliferation in Astrocytes --- p.90 / Chapter 3.2 --- Effect of Cytokines on Glucose Uptake in Rat Astrocytes --- p.95 / Chapter 3.2.1 --- Basal level of Glucose Uptake in Astrocytes and Effects of Cytokines on Glucose Uptake in Astrocytes --- p.95 / Chapter 3.2.2 --- Signaling Cascade of LPS- and TNF-α-induced Glucose Uptake in Astrocytes --- p.120 / Chapter (A) --- TNFR Subtypes Mediating TNF-a-induced Glucose Uptake --- p.121 / Chapter (B) --- MAPK --- p.125 / Chapter (C) --- PKA --- p.133 / Chapter (D) --- NFkB --- p.139 / Chapter (E) --- Other Mechanisms / Signalling molecules --- p.150 / Chapter (1) --- Interaction with β-Adrenegic Mechanism / Chapter (2) --- Role of cGMP --- p.154 / Chapter (3) --- Effect of Mg2+ on LPS- / TNF-α- induced Glucose Uptake in Astrocytes --- p.156 / Chapter (4) --- Possible Involvement of IGF-1 System --- p.160 / Chapter 3.2.3 --- Summary --- p.163 / Chapter 3.3 --- Effects of LPS and Cytokines on AA Accumulation in Astrocytes --- p.164 / Chapter Chapter 4 --- Discussion / Chapter 4.1 --- Role of Calcium ions (Ca2+) in TNF-α-induced Astrocyte Proliferation --- p.177 / Chapter 4.1.1 --- Drastic Changes in Extracellular Ca2+ Caused Astrocyte Death --- p.178 / Chapter 4.1.2 --- Extraordinary Role of Ca2+ in Astrocytes Survival --- p.178 / Chapter 4.1.3 --- Elevation of [Ca2+]i Reduced Astrocyte Viability --- p.180 / Chapter 4.1.4 --- Failure of Verapamil to Block TNF-α-induced Astrocyte Proliferation --- p.182 / Chapter 4.2 --- Hypothesis for the Relationship between Cytokines and Energy Metabolism --- p.185 / Chapter 4.2.1 --- Mechanism and Signaling Cascade of the Elevated Glucose Uptake --- p.186 / Chapter 4.2.2 --- Increased Glucose Uptake by Cytokines: Friend or Foe? --- p.191 / Chapter 4.2.3 --- Depletion of AA Pool by LPS --- p.194 / Chapter 4.2.4 --- Possible Bedside Application of the Findings --- p.195 / Chapter 4.3 --- Prospects of This Study and Concluding Remarks --- p.197 / Appendix --- p.201 / References --- p.202