Medicine and Health Sciences Commons^™

Human Amniotic Fluid Stem Cells Do Not Differentiate Into Dopamine Neurons In Vitro Or After Transplantation In Vivo., Angela E Donaldson, Jingli Cai, Ming Yang, Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

Although embryonic stem (ES) cells can generate dopamine (DA) neurons that are potentially useful as a cell replacement therapy in Parkinson's disease (PD), associated ethical and practical concerns remain major stumbling blocks to their eventual use in humans. In this study, we examined human amniotic fluid stem (hAFS) cells derived from routine amniocenteses for their potential to give rise to DA neurons in vitro and following transplantation into the 6-hydroxydopamine-lesioned rat brain. We show that undifferentiated hAFS cells constitutively expressed mRNAs and proteins typical of stem cells but also cell derivatives of all three germ layers, including neural progenitors/neurons (nestin, …

Effects Of Genetic Deficiency Of Cyclooxygenase-1 Or Cyclooxygenase-2 On Functional And Histological Outcomes Following Traumatic Brain Injury In Mice, Matthew L. Kelso, Stephen W. Scheff, James R. Pauly, Charles D. Loftin

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Neuroinflammation contributes to the pathophysiology of acute CNS injury, including traumatic brain injury (TBI). Although prostaglandin lipid mediators of inflammation contribute to a variety of inflammatory responses, their importance in neuroinflammation is not clear. There are conflicting reports as to the efficacy of inhibiting the enzymes required for prostaglandin formation, cyclooxygenase (COX) -1 and COX-2, for improving outcomes following TBI. The purpose of the current study was to determine the role of the COX isoforms in contributing to pathological processes resulting from TBI by utilizing mice deficient in COX-1 or COX-2.

RESULTS: Following a mild controlled cortical impact injury, …

Triptolide Is A Potential Therapeutic Agent For Alzheimer’S Disease, Matthew Allsbrook

Theses and Dissertations

Mounting evidence indicates an involvement of inflammation in the pathogenesis of Alzheimer’s disease. While there are other mechanisms involved, it is this role of inflammatory processes that we wish to investigate. Triptolide is the major constituent in the Chinese herb, Tripterygium wilfordii Hook F, and has been used for centuries as part of Chinese herbal medicine. The four ringed structure has close homology to drugs of the steroid class and it has been shown to be beneficial as an anti-inflammatory for rheumatoid arthritis and for treatment of certain cancers. The aim of this study was to evaluate the potential therapeutic …

Cannabinoid Receptor Type 2 Activation Induces A Microglial Anti-Inflammatory Phenotype And Reduces Migration Via Mkp Induction And Erk Dephosphorylation, Edgar A. Romero-Sandoval, Ryan Horvath, Russell P. Landry, Joyce A. Deleo

Dartmouth Scholarship

Cannabinoid receptor type 2 (CBR2) inhibits microglial reactivity through a molecular mechanism yet to be elucidated. We hypothesized that CBR2 activation induces an anti-inflammatory phenotype in microglia by inhibiting extracellular signal-regulated kinase (ERK) pathway, via mitogen-activated protein kinase-phosphatase (MKP) induction. MKPs regulate mitogen activated protein kinases, but their role in the modulation of microglial phenotype is not fully understood.

The Role Of Acanthamoeba Culbertsoni Serine Proteases In Abating Microglial-Like Cell Cytokines And Chemokines, Jenica Harrison

Theses and Dissertations

Acanthamoeba culbertsoni is an opportunistic free-living amoeba that is causative of granulomatous amoebic encephalitis (GAE), a chronic and often fatal central nervous system (CNS) disease that is most prevalent in immune compromised individuals. One hallmark of this disease is the formation of granulomas within the CNS, which are commonly absent in immune compromised individuals. Granulomas are usually composed of amoebae, microglia (CNS macrophages), macrophages, T cells, B cells, and neutrophils. Previous studies have demonstrated that microglia respond to Acanthamoeba by producing pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF)-α, interleukin (IL)-1α, and IL-1β. In addition, activated microglia and macrophages …

Immunomodulatory Effects Of Novel Therapies For Stroke, Aaron A. Hall

USF Tampa Graduate Theses and Dissertations

Each year, approximately 795,000 people suffer a new or recurrent stroke. About 610,000 of these are first attacks, and 185,000 are recurrent attacks (Carandang et al. 2006). Currently the only FDA approved treatment for ischemic stroke is recombinant tissue plasminogen activator (Alteplase) (Marler and Goldstein 2003). Unfortunately its use is restricted to a short, 4.5 hour, time window. Two promising therapies in the treatment of stroke at delayed timepoints are human umbilical cord blood cells (HUCBC) and the sigma receptor agonist DTG

The first series of experiments were conducted to characterize the effects of sigma receptors on various aspects of …

Oncostatin M-Induced Gene Expression And Regulation In Astrocytes And Microglia, Brandi Janece Baker

All ETDs from UAB

Astrocytes and microglia are specialized glial cells of the Central Nervous System (CNS) that modulate neural activity and regulate immunological and inflammatory events. These cells perform their functions, in part, through the secretion of soluble mediators such as cytokines and chemokines. However, in response to the same neurological insult or inflammatory stimuli, the responses of these cells can vary greatly. This notion of differential responses was examined in our studies using Oncostatin M (OSM). OSM is a member of the IL-6 family of cytokines, which can be produced by microglia, astrocytes, neurons, and infiltrating leukocytes in the CNS, and is …

Neuroinflammation And Fragile X Syndrome: Regulation By Glycogen Synthase Kinase-3, Christopher Joseph Yuskaitis

All ETDs from UAB

Neuroinflammation and Fragile X syndrome (FXS) are two particularly devastating neurologic conditions for which no adequate treatment exists and much is still unknown about the underlying cellular and molecular processes. Neuroinflammation contributes to the pathogenesis of many neurologic and psychiatric disorders, thus treatment of the underlying inflammation has broad implications. FXS is the most common cause of inherited intellectual and developmental delay and one of the few known genetic causes of autism. Neuroinflammation and FXS have potential links with glycogen synthase kinase-3 (GSK3) and its inhibitor, lithium. Therefore, the overall goal of this research was to examine the role of …

Innate Immune Responses In The Central Nervous System Following Toll-Like Receptor (Tlr) 7 And Tlr9 Activation, Niranjan Babu Butchi

LSU Doctoral Dissertations

Activation of astrocytes and microglia and the production of proinflammatory cytokines and chemokines are often associated with virus infection in the central nervous system (CNS) as well as a number of neurological diseases of unknown etiology. These inflammatory responses may be initiated by recognition of pathogen-associated molecular patterns that stimulate toll-like receptors (TLRs). Recent studies demonstrated that TLR9 family receptors play a role in neuropathogenesis and the agonists of these receptors may be used in therapeutics treatment of brain tumors and viral infections. However, we lack the basic understanding of how these receptors function in the CNS. In the present …