Development and assessment of in vitro simulation approaches to intracerebral haemorrhage

RB Pathology;RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry;RZ Other systems of medicine

Zarros, Apostolos ; Baillie, George S.

University:University of Glasgow

Department:Institute of Cardiovascular and Medical Sciences

关键词: Neuropathology, intracerebral haemorrhage, stroke, intracerebral haematoma, perihaematomal penumbra, in vitro simulation approaches, mHippoE-14, embryonic murine hippocampal cell-line, oligomycin-A, ferrum, haemin, characterization, foetal bovine serum-deprivation, FBS-deprivation, real-time cellular response analysis, xCELLigence technology, high-throughput, parametropoiesis, metaptosis, metaptotic phase, pathopoietic phase, cellular response, CR, normalized cellular response, nCR, metaptotic index, mi, index of metaptotic adaptability, μi, cytomorphology, phase-contrast microscopy, mHippoE-14 classification, mHippoE-14 atlas, development, assessment, neuroprotective drugs, deferoxamine, DFO, cytidine-5’-diphosphocholine, CDP-Ch, neuronal markers’ expression, alpha 1 subunit of sodium / potassium adenosine triphosphatase, α1 Na+,K+-ATPase, choline acetyltransferase, ChAT, synapsin I, haeme oxygenase 1, HO-1, neurochemical assessment, acetylcholinesterase, AChE, proteomic profiling, cytokine arrays, neuropathopoiesis, drug-screening tools.;   

Others  :  http://theses.gla.ac.uk/8119/7/2017ZarrosPhD.pdf

来源: University of Glasgow

【 摘 要 】

This current PhD Thesis in Neuropathology focuses on the development and assessment of in vitro simulation approaches to intracerebral haemorrhage. The PhD Thesis provides a clinical and experimental neuropathological overview of intracerebral haemorrhage as well as an account of the in vitro simulation approaches to the disease, before proceeding to the presentation of the experimental work designed and performed by the author. The development of the herein presented in vitro simulation approaches to intracerebral haemorrhage was based on the use of an immortalized embryonic murine hippocampal cell-line (mHippoE-14) and its response to oligomycin-A and ferrum or haemin under appropriately selected conditions (aiming to simulate the natural history of the disease in a more reliable manner). The PhD Thesis provides a characterization of the mHippoE-14 cell-line (through a real-time cellular response analysis and a cytomorphological characterization), before proceeding to the actual experimental justification of the conditions chosen for the development of the herein presented in vitro simulation approaches to intracerebral haemorrhage, and their assessment. The latter was performed through the undertaking of: (a) real-time cellular response analysis, (b) cytomorphological assessment, (c) profiling of neuronal markers’ expression, (d) neurochemical assessment, and (e) proteomic profiling. All experiments were performed at the University of Glasgow. The current PhD Thesis also provides a critical appraisal of: (a) the utility, novelty and limitations of the developed in vitro simulation approaches, and (b) the positioning of the developed in vitro simulation approaches within the neuropathopoietic context.