Current Search: Granulocyte-colony stimulating factor (x)
View All Items
- Title
- EFFECT OF G-CSF GENE THERAPY IN A MICROGLIA MODEL OF STROKE.
- Creator
- Velasquez Saldarriaga, Esteban, Wu, Jang-Yen, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Cerebrovascular events (stroke) are a significant cause of morbidity and mortality worldwide. Ischemic stroke accounts for ~85% of all strokes and is caused by the blockade of blood flow to a certain area of the brain, resulting in oxygen and nutrient deprivation and ultimately cell death. Cerebral ischemia induces a strong neuroinflammatory response that contributes to tissue damage and is driven by changes in the gene expression profile and phenotype of brain cells including neurons,...
Show moreCerebrovascular events (stroke) are a significant cause of morbidity and mortality worldwide. Ischemic stroke accounts for ~85% of all strokes and is caused by the blockade of blood flow to a certain area of the brain, resulting in oxygen and nutrient deprivation and ultimately cell death. Cerebral ischemia induces a strong neuroinflammatory response that contributes to tissue damage and is driven by changes in the gene expression profile and phenotype of brain cells including neurons, astrocytes, and microglia. Microglia are the resident immune and phagocytic cells of the central nervous system. They rapidly respond to ischemia by migrating to the site of injury and modulating the inflammatory response there. Although microglia may play a deleterious role in the acute phase of stroke, evidence suggests that they play an important role in the reduction of excitotoxic injury as well as in neurogenesis during the tissue regeneration phase. Granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor that has shown beneficial effects in models of ischemic stroke. G-CSF exerts its neuroprotective effects through different mechanisms including mobilization of haemopoietic stem cells, angiogenesis, neurogenesis, anti-inflammation, and anti-apoptosis. However, its effect on microglia is not well understood yet. The main objective of this project was to evaluate the protective and anti-inflammatory effect of G-CSF gene therapy against glutamate cytotoxicity in the human microglial clone 3 cell line (HMC3). Our results show that although G-CSF gene therapy did not significantly protect HMC3 cells against glutamate induced cell death, it reduced the expression levels of pro-inflammatory proteins NF-κB p65, IL-1β and IL-6, while increasing the phosphorylation of Akt, a regulator of cell survival and proliferation.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FA00013821
- Subject Headings
- Stroke, Granulocyte Colony-Stimulating Factor, Cerebrovascular disease, Microglia
- Format
- Document (PDF)
- Title
- THERAPEUTIC STRATEGIES USING SULINDAC AND G-CSF GENE THERAPY FOR NEUROLOGICAL DISEASE.
- Creator
- Chen, Belinda, Prentice, Howard, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Alzheimer’s disease is a neurodegenerative disease that causes cognitive dysfunction and leads to progressive memory loss and behavioral impairment. About 60% to 80% of dementia cases are attributed to Alzheimer’s disease and currently afflict about 50 million people worldwide. Although it primarily affects people over the age of 65, a person’s risk for developing Alzheimer’s disease earlier can depend on factors such as a family history (genetic inheritance) or experiencing an ischemic...
Show moreAlzheimer’s disease is a neurodegenerative disease that causes cognitive dysfunction and leads to progressive memory loss and behavioral impairment. About 60% to 80% of dementia cases are attributed to Alzheimer’s disease and currently afflict about 50 million people worldwide. Although it primarily affects people over the age of 65, a person’s risk for developing Alzheimer’s disease earlier can depend on factors such as a family history (genetic inheritance) or experiencing an ischemic stroke event. Current treatments for Alzheimer’s disease include behavioral therapy and drug treatment that can lessen the severity of symptoms but cannot stop progression indefinitely. Sulindac is a non-steroidal anti-inflammatory drug that, by a mechanism independent of its anti-inflammatory properties, has shown to express a preconditioning response to protect from oxidative damage. Granulocyte colony stimulating factor is a hematopoietic glycoprotein that can stimulate the production of granulocytes and stem cells that has proven to provide neuroprotection in models of ischemic stroke via mechanisms including anti-apoptosis and anti-inflammation. In this in vitro study, the potential neuroprotective effects of Sulindac is measured against the effects of oxidative stress when subjected to hypoxia and reperfusion. Regarding un-transfected SHSY-5Y cells, hypoxia was demonstrated to lower cell viability starting at a period of 12 hours. It was found that a low concentration of Sulindac (200 uM) was effective in protecting SHSY-5Y cells against oxidative stress and overall lowering the rate of cell death in the event of hypoxic and reperfusion injury. When SHSY-5Y cells were transfected with Swedish APP mutation, cell viability was also markedly decreased in hypoxic conditions. However when treated with a concentration of 600 uM of Sulindac, cell viability levels were near matched with its normoxic counterparts
Show less - Date Issued
- 2022
- PURL
- http://purl.flvc.org/fau/fd/FA00014021
- Subject Headings
- Sulindac, Granulocyte-colony stimulating factor, Genetic Therapy, Alzheimer Disease
- Format
- Document (PDF)
- Title
- G-CSF GENE THERAPY FOR BRAIN DISEASES AND/OR SICKLE CELL ANEMIA.
- Creator
- Basilio, Stefan, Prentice, Howard, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Ischemic stroke is defined as a blockage or reduced flow of blood to select areas of brain tissue due to either plaque formation or buildup of blood clots in the small blood vessels. A characteristic of sickle cell anemic patients is the potential for them to experience a similar type of blockage due to the sticky nature of the sickled red blood cells as well as defective oxygen delivery to the brain. Because of this similarity, sickle cell anemia may represent a good animal research model...
Show moreIschemic stroke is defined as a blockage or reduced flow of blood to select areas of brain tissue due to either plaque formation or buildup of blood clots in the small blood vessels. A characteristic of sickle cell anemic patients is the potential for them to experience a similar type of blockage due to the sticky nature of the sickled red blood cells as well as defective oxygen delivery to the brain. Because of this similarity, sickle cell anemia may represent a good animal research model for therapeutic intervention based on stroke models. In recent studies, Granulocyte-Colony Stimulating Factor (GCSF), has been shown to exhibit a robust range of neuroprotective properties against neurological disorders including ischemic stroke through preservation of the endoplasmic reticulum (ER) by modulating various ER stress pathways. Through cognitive deficit analysis in the form of behavioral and locomotor experiments in addition to in situ biomarker analysis by way of western blotting and immunohistochemistry, we found that G-CSF gene therapy exhibited neurogenic and neuroprotective effects in ischemic mouse models and could possibly serve as a good therapy for other diseases that share similar pathology to stroke.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FA00013787
- Subject Headings
- Sickle cell anemia, Stroke, Granulocyte Colony-Stimulating Factor, Gene therapy
- Format
- Document (PDF)