499 research outputs found
Targeting Pro-Inflammatory Function of Microglia Using Small Molecules to Combat Neurodegeneration
Get PDFMicroglia are the brain’s resident immune cells that are responsible for maintaining homeostasis in healthy conditions. During injury or infection, resting microglia get activated and produce pro-inflammatory cytokines such as IL-1b, IL-1a, IL-6, etc. along with reactive oxygen species like nitric oxide (NO) to combat neuroinflammatory diseases such as Alzheimer’s disease (AD). Inflammation is characterized by the activation of resident-immune cells in the brain called microglia that respond to the eat-me signals released by the toxic amyloid beta peptides as well as the dying neurons in the microenvironment. Recent studies have shown that activated microglia induce neuronal death by secreting IL-1a, TNF-a, and C1q. However, the cellular and molecular mechanisms in this process are not well understood. Furthermore, it has been previously shown that IL-1a and TNF-a promote neuronal death via the activation of astrocytes during inflammation. We used BV2 mouse microglia to investigate the IL-1a and TNF-a cytokine production in response to LPS activation using enzyme-linked immunosorbent assay (ELISA). In addition, the viability of the cells along with their NO production was evaluated using cell titer blue assay (CTB) and Griess assay. In this study, we show that small molecules can be used in single treatment and in combination to combat the inflammatory functions of microglia. These small molecules that modulate microglial functions may play an important role in developing new therapeutics for neuroinflammation
Modelling Paediatric Bones: Estimating mechanical strength of paediatric femurs using a personalised computational modelling technique.
Get PDFForty four million children, under the age of 15, in Europe have been physically abused, as suggested by a 2013 report (World Health Organization, 2013); with children under the age of three being more prevalent to repeated abuse as they can’t narrate the incident themselves (Ravichandiran, et al., 2010). However assessing the mechanisms of these injuries and determining which are accidental, depends largely on clinician’s judgement, for which there is little reliable evidence. More accurate diagnoses can be made by quantitatively analysing the forces required to fracture these bones by creating individualised biomechanical models of bones. The aim of this project is to investigate the fracture mechanism of paediatric femurs using personalised finite element modelling. Thirty computational models of the femur were created using CT. Each model was subjected to four point bending simulations and the force to failure was estimated. It was found that the force to fracture increases as the age, weight and height increases. In the future, further mechanical simulations can be applied to these models and the process repeated for the tibia, and the predicted results can be used to compare against injury data collected in the clinic in order to further develop this modelling framework
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