by Wu Kwok Hang. / Thesis (M.Ph.)--Chinese University of Hong Kong, 1988. / Bibliography: leaves 213-229.

Skeletal muscle atrophy is the most common clinical disorder of skeletal muscle and typically occurs as a secondary consequence of fasting, disuse, acute and chronic illness, and aging. It can lead to prolonged recovery and loss of independent living. Of similar clinical significance, one third of Americans are obese and at risk for metabolic syndrome. Interestingly recent studies have demonstrated that both metabolic syndrome and obesity diminish skeletal muscle strength, power, and endurance. However, there are no effective pharmacological treatments for these debilitating effects on skeletal muscle. This is largely due to the fact that the molecular mechanisms underlying its pathogenesis remain uncharacterized. We have recently identified ursolic acid (UA) as a small molecule inhibitor of muscle atrophy. In the absence of atrophy-inducing stress, UA-supplemented chow elicited muscle hypertrophy with little adiposity in mice. To further evaluate these data, mice were subjected to a high fat diet (HFD) with or without UA supplementation, or a standard chow (SC) control. Our data indicates that UA-supplemented HFD mitigates muscle atrophy and adiposity, while HFD significantly reduces muscle mass compared to SC. Furthermore, mice fed a HFD exhibited increased adiposity and reduced muscle mass, strength, and fiber diameter when compared to SC controls. Molecular analysis revealed diminished protein content and increased triglycerides. Gene expression analysis revealed a reduction in Pgc1α, a critical gene that regulates oxidative metabolism and mitochondrial biogenesis. Additionally, we found decreased expression of hormonal receptors AR, involved in signaling of testosterone, and Thrα, involved in signaling of thyroid hormones. Taken together, these data suggest that alterations in gene expression resulting from diet-induced obesity are an atrophy-inducing stress that may function by disrupting metabolic and hormonal signaling.

Thesis (Ph. D.)--University of Virginia, 2006. / Includes bibliographical references. Also available online through Digital Dissertations.

Rationale: Ng et al. (2008) demonstrated that sub-acute hippocampal atrophy occurred between 4.5 and 24 months following moderate-to-severe traumatic brain injury (TBI); it remains to be determined if atrophy occurred before 24 months. Objectives: (1) to determine if sub-acute hippocampal atrophy occurs by the first year of injury; (2) to determine associated clinical and demographic variables. Methods: Ten moderate-to-severe TBI patients underwent MRI at 5 and 12 months post-injury. Glasgow Coma Scale (GCS) and demographic variables were correlated with change. Results: Significant hippocampal volume decreases were observed for right (P< 0.002, Cohen’s d= 0.34) and left (P< 0.036, Cohen’s d= 0.22) sides. GCS was significantly correlated with right (r= -0.663, P< 0.037), but not left percent hippocampal volume change (r= -0.327, P< 0.356). No significant correlations were observed for demographic variables. Conclusion: Sub-acute hippocampal atrophy occurs between 5 and 12 months post-injury and is associated with injury severity.

Rationale: Ng et al. (2008) demonstrated that sub-acute hippocampal atrophy occurred between 4.5 and 24 months following moderate-to-severe traumatic brain injury (TBI); it remains to be determined if atrophy occurred before 24 months. Objectives: (1) to determine if sub-acute hippocampal atrophy occurs by the first year of injury; (2) to determine associated clinical and demographic variables. Methods: Ten moderate-to-severe TBI patients underwent MRI at 5 and 12 months post-injury. Glasgow Coma Scale (GCS) and demographic variables were correlated with change. Results: Significant hippocampal volume decreases were observed for right (P< 0.002, Cohen’s d= 0.34) and left (P< 0.036, Cohen’s d= 0.22) sides. GCS was significantly correlated with right (r= -0.663, P< 0.037), but not left percent hippocampal volume change (r= -0.327, P< 0.356). No significant correlations were observed for demographic variables. Conclusion: Sub-acute hippocampal atrophy occurs between 5 and 12 months post-injury and is associated with injury severity.

No description available.

Preliminary novel research findings indicate that a subset of individuals with moderate to severe traumatic brain injury show bilateral hippocampal atrophy progressing beyond the acute stage post-injury. The present study proposes a novel, integrated model of neuroprotection against subacute hippocampal atrophy (i.e., atrophy occurring beyond the initial 3 months post-injury) via environmental enrichment, drawing on theoretical models and research findings from the fields of environmental enrichment, brain and cognitive reserve, and neuroplastic models of functional recovery from brain injury. Objectives: (a) to examine the relationship between environmental enrichment factors and subacute hippocampal atrophy and (b) to examine the relationship between subacute hippocampal atrophy and return to productivity. Design: Retrospective observational within-subjects. Participants: Patients (N=21) with moderate to severe TBI. Measures: Primary predictors: Self-report ratings of environmental enrichment factors (i.e., hours of cognitive, physical, and social activities, meditation/prayer, and therapy). Primary outcome: hippocampal volume change between 5 months and 24+ months post-injury based on initial and follow-up MRI scans; Brain Injury Community Rehabilitation Outcome Scales-39 (BICRO-39). Results: Generalized environmental enrichment (i.e., an aggregate of cognitive, physical, and social activity) was significantly negatively correlated with subacute bilateral hippocampal atrophy (p<.05). Cognitive activity was the environmental enrichment element that accounted for the greatest degree of variance (32%) in subacute bilateral hippocampal atrophy (p<.01). Frequency of meditation/prayer was significantly negatively correlated with right hippocampal subacute atrophy (<.05) after controlling for socioeconomic status and generalized environmental enrichment. Level of education and pre-injury occupational attainment did not correlate with subacute hippocampal atrophy. Conclusion: Findings suggest that a fixed degree of neural reserve at the time of brain injury may not confer neuroprotection against structural pathology in the manner suggested by the present study’s proposed model of neuroprotection via environmental enrichment. Instead, findings suggest that in order for environmental enrichment to positively modulate susceptibility to subacute hippocampal atrophy post-TBI, environmental enrichment exposure must occur during the subacute phase post-injury rather than prior to injury.

Preliminary novel research findings indicate that a subset of individuals with moderate to severe traumatic brain injury show bilateral hippocampal atrophy progressing beyond the acute stage post-injury. The present study proposes a novel, integrated model of neuroprotection against subacute hippocampal atrophy (i.e., atrophy occurring beyond the initial 3 months post-injury) via environmental enrichment, drawing on theoretical models and research findings from the fields of environmental enrichment, brain and cognitive reserve, and neuroplastic models of functional recovery from brain injury. Objectives: (a) to examine the relationship between environmental enrichment factors and subacute hippocampal atrophy and (b) to examine the relationship between subacute hippocampal atrophy and return to productivity. Design: Retrospective observational within-subjects. Participants: Patients (N=21) with moderate to severe TBI. Measures: Primary predictors: Self-report ratings of environmental enrichment factors (i.e., hours of cognitive, physical, and social activities, meditation/prayer, and therapy). Primary outcome: hippocampal volume change between 5 months and 24+ months post-injury based on initial and follow-up MRI scans; Brain Injury Community Rehabilitation Outcome Scales-39 (BICRO-39). Results: Generalized environmental enrichment (i.e., an aggregate of cognitive, physical, and social activity) was significantly negatively correlated with subacute bilateral hippocampal atrophy (p<.05). Cognitive activity was the environmental enrichment element that accounted for the greatest degree of variance (32%) in subacute bilateral hippocampal atrophy (p<.01). Frequency of meditation/prayer was significantly negatively correlated with right hippocampal subacute atrophy (<.05) after controlling for socioeconomic status and generalized environmental enrichment. Level of education and pre-injury occupational attainment did not correlate with subacute hippocampal atrophy. Conclusion: Findings suggest that a fixed degree of neural reserve at the time of brain injury may not confer neuroprotection against structural pathology in the manner suggested by the present study’s proposed model of neuroprotection via environmental enrichment. Instead, findings suggest that in order for environmental enrichment to positively modulate susceptibility to subacute hippocampal atrophy post-TBI, environmental enrichment exposure must occur during the subacute phase post-injury rather than prior to injury.

名古屋大学博士学位論文 学位の種類:博士（医療技術学）（課程）学位授与年月日:平成21年3月25日

Dissertation (MSc)--University of Stellenbosch, 2008. / Bibliography. Also available via the Internet.