Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

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A research report submitted to the Faculty of Health Sciences, the University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science in Medicine in Child Health Neurodevelopment Johannesburg, 2013 / Human Immunodeficiency Virus (HIV) infection in infancy may influence the developing brain and lead to adverse neurodevelopmental consequences. We aim to describe the neurodevelopmental characteristics of a cohort of young children infected with HIV prior to antiretroviral therapy (ART) initiation and after achieving viral suppression. A retrospective analysis of data collected as part of a randomised equivalence trial between April 2005 and May 2009, at a hospital in Johannesburg, South Africa. 195 HIV-infected children under 2 years of age were assessed. A simple, inexpensive screening questionnaire (Ages and Stages Questionnaire - ASQ) was used to identify neurodevelopmental delays. The ASQ was administered prior to ART initiation, and again after viral suppression on a protease inhibitor-based regimen had been achieved. Median age pre-ART was 8.8 months (range 2.2 - 24.9), 53.9% were male. Mean time to viral suppression was 9.4 months (range 5.9 - 14.5) and the ASQ was administered to 108 caregivers at this time. Compared to pre-ART, at viral suppression, there was significant reduction in the proportion of children failing the gross motor (31.5% vs. 13%, p<0.01), fine motor (21.3% vs. 10.2%, p=0.02), problem solving (26.9% vs. 9.3%, p<0.001) and personal social (17.6% vs. 7.4%, p=0.02) domains. The proportion of children failing the communication domain was similar at each time point (14.8% vs. 12%, p=0.61). At time of viral suppression 10.2% failed at least one of the five domains. Achieving viral suppression on ART resulted in significant improvements in the neurodevelopmental function of young HIV-infected children, however, neurodevelopmental problems still persisted in a large proportion. Appropriate screening for neurodevelopmental delay and timely referral could help improve outcomes.

The central nervous system controls many physiological processes including energy metabolism, immune response, reproduction, and development. In turn, hormones synthesized in and secreted by peripheral organs can be transported across the blood-brain barrier to modulate the development of the brain, the formation of new neurons, neural activity, behavior, and the secretion of brain-derived hormones. The central control of bone mass, mediated by the adipocyte-derived hormone leptin, has raised questions of whether the skeleton may signal back to the brain. In recent years, the Karsenty laboratory has uncovered the endocrine role of the bone-derived hormone osteocalcin. Through the use of a vast array of genetic tools, the Karsenty lab has discovered that osteocalcin is a potent regulator of glucose homeostasis, adaptation to exercise, energy metabolism, and male fertility. The multifunctional role of osteocalcin led us to hypothesize that it may act as a molecular means of communication between the skeleton and the brain. We asked whether osteocalcin could regulate brain development during embryogenesis and behavioral functions in adulthood. In addressing these questions, we observed that bone-derived osteocalcin crosses the blood-brain barrier, accumulates in discrete parts of the brain including the hippocampus, and binds to several neuronal populations to favor the synthesis of monoamine neurotransmitters (serotonin, dopamine, and norepinephrine), and to impede the synthesis of the inhibitory neurotransmitter, GABA. Osteocalcin-/- mice have increased anxiety and depression and impaired learning and memory when compared to WT littermates. We also uncovered that the absence of maternal osteocalcin during embryogenesis hinders brain development and causes defects in spatial learning and memory in the adult offspring. Upon characterizing the necessity of osteocalcin for brain development and cognitive function, we investigated whether bone health is a determinant of cognition, and whether osteocalcin may be sufficient to reverse age-related cognitive decline. In addressing the first question, we found that impairment in either bone formation or bone resorption negatively impacts both anxiety and memory. In addressing the second question, we found that osteocalcin is also necessary for the beneficial effect of young blood on cognitive functions. Finally, we observed reduced anxiety and improved memory in aged mice receiving osteocalcin peripherally. This action appears to require an increase in brain-derived neurotrophic factor levels in the hippocampus. Against the backdrop of our progressively aging population, it is important for future studies to determine whether osteocalcin may act therapeutically in humans to treat age-related cognitive decline. Additionally, to identify potential drug targets, it is important to fully characterize the molecular mechanism by which osteocalcin acts on neurons.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 7 uppsatser.

Su Huan Xing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 79-89). / Abstracts in English and Chinese. / Abstract --- p.i / 中文摘要 --- p.iii / Acknowledgements --- p.iv / Abbreviations Frequently Used --- p.v / Table of contents --- p.vi / Chapter Chapter1 --- General Introduction --- p.1 / Chapter Chapter2 --- Effects of an intravitreal optic nerve graft on the sprouting and regeneration of axotomized retinal ganglion cells --- p.17 / Chapter Chapter3 --- Effects of an intravitreal pre-injured optic nerve graft on the sprouting and regeneration of axotomized retinal ganglion cells --- p.44 / Chapter Chapter4 --- Effects of co-transplantation of an optic nerve graft and a peripheral nerve graft into the vitreous body on the sprouting and regeneration of axotomized retinal ganglion cells --- p.60 / Chapter Chapter5 --- General discussion --- p.74 / References --- p.79 / Tables --- p.90

A thesis submitted to the Faculty of Health Sciences of the University of the Witwatersrand, for the degree of Master of Science, Johannesburg, 2012 / HIV continues to affect thousands of children in South Africa. HIV not only has a negative impact on growth, morbidity and mortality but also adversely affects neurodevelopment. The virus is able to enter the central nervous system and cause damage which results in encephalopathy. A high percentage of infants infected with HIV are delayed. The roll out of HAART in South Africa was started in 2004 and in 2010 new guidelines to improve access were implemented. Although HAART is effective in improving growth, decreasing morbidity and mortality its effects on neurodevelopment are generally unknown. Very little high quality research has been done on the effects of HAART on neurodevelopment especially in developing countries and on infants.