Stroke

Stroke is a major health problem in Saudi Arabia that impacts the health outcomes of adults and elderly persons. No matter its severity, stroke is a stressful life event not only for the survivors but their family caregivers as well. Uncertainty is one of the major problems facing family caregivers caring for persons with a stroke. Uncertainty affects overall health outcomes and the quality of life of family caregivers caring for persons with strokes. Current research has not yet identified the meaning of the uncertainty of family caregivers of persons with strokes during hospitalization in Saudi Arabia. The purpose of this study was to gain an in-depth understanding of the meaning of uncertainty experienced by family caregivers of persons in the hospital who have survived strokes.
This study used a phenomenological design. Data were collected through in-depth face-to-face and online semi-structured interviews with 15 family caregivers using openended questions. Participants were recruited from inpatient medical units and stroke care units in multi acute care hospitals in Saudi Arabia. The interviews were recorded, transcribed verbatim, translated, and analyzed using the hermeneutic phenomenological unitary caring research method. NVivo software (Version 12) was used to manage the qualitative data.

Providing family caregiving during transitional care of a stroke patient is the most challenging for family caregivers. This is because of the shift in the care environment from a hospital with an organizational culture to a home with a traditional culture. Yet, cultural influences on family caregiving during transitional care are not well studied. This ethnographic study aims to describe the family caregiving of older Thai-Isan stroke survivors through the transition from hospital to home. This study employs Lininger's culture care theory (CCT) as the theoretical framework and utilizes the ethnonursing method to discover cultural knowledge. Data was collected through a demographic questionnaire, participant observations, and a semi-structured interview. Data was analyzed using the Four Phases of the Data Analysis Enabler. Fifteen dyads of older stroke patients and their family caregivers were recruited following the inclusion and exclusion criteria. The research settings included Srinagarind Hospital units and key informants’ homes in a Thai-Isan community.

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, 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.

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 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.

Stroke is one of the leading causes of human death in the United States. The debilitating effects of an ischemic stroke are due to the fact that mammalian neurons are highly susceptible to hypoxia and subsequent oxygen reperfusion. From studies in Drosophila melanogaster, cGMP-dependent Protein Kinase (PKG) enzyme is thought to affect anoxia tolerance by modifying the electrical current through potassium ion channels. In this research, two animal models were employed: Drosophila melanogaster and mammalian neurons exposed to stroke-like conditions. First, in vivo studies using Drosophila were performed to further our knowledge about the differences between the naturally occurring variants of the Drosophila foraging gene, which shows different protein levels of PKG. Mitochondrial density and metabolic activity between two fly genotypes exposed to anoxia and reoxygenation were compared. It was found that flies with less enzyme potentially showed mitochondrial biogenesis and higher metabolic rates upon reoxygenation. Next, in vivo studies where PKG enzyme was activated pharmacologically were performed; it was found that the activation of the cGMP/PKG pathway led to neuroprotection upon anoxia and reoxygenation. Furthermore, this model was translated into the in vitro model using Drosophila cells. Instead of anoxia and reoxygenation, hypoxia mimetics and hydrogen peroxide were used to induce cellular injury. After showing the cGMP/PKG pathway activation-induced cell protection, the potential downstream targets of the molecular signaling as well as underlying biochemical changes were assessed. It was found that mitochondrial potassium ion channels were involved in the protective signaling and the signaling modulated metabolic function. Furthermore, it was found that acidosis protected Drosophila cells from cell death, metabolic disruption, and oxidative stress. Finally, this research was translated to a mammalian in vitro model of neuronal damage upon stroke-like conditions; there, it was demonstrated that the cGMP/PKG pathway activation in rat primary cortical neurons and human cortical neurons was protective from low oxygen and acute oxidative stress. The results of this study lead to a better understanding of molecular mechanisms taking place during low oxygen and oxidative stresses. Consequently, this knowledge may be used to identify potential therapeutic targets and treatments that may prevent detrimental neurological effects of an ischemic stroke in humans.