Anti-β-amiloīda terapija un uzlabota metodoloģija zāļu intracerebrālaiievadei apvienojumā ar kvantitatīvo histopatoloģisko analīzi Alcheimera slimības peļu modeļos
Date
2022
Authors
Upīte, Jolanta
Journal Title
Journal ISSN
Volume Title
Publisher
Latvijas Universitāte
Abstract
Alcheimera slimība (AD) ir progresējoša un neatgriezeniska neirodeģeneratīva slimība. Pašreiz pieejamās medikamentozās terapijas ir simptomātiskas un īslaicīgi efektīvas. Zāļu nokļūšana smadzenēs noteiktiem savienojumiem var tikt apgrūtināta un piemērota vielu ievades sistēma, kas spētu nodrošināt dažādu savienojumu BBB šķērsošanu, ir mini-osmotiskie sūkņi. Promocijas darba mērķis bija novērtēt pretiekaisuma zāļu vielas iedarbību uz dažādiem AD patofizioloģiskiem mehānismiem, kā arī pilnveidot metodoloģiju intracerebrālai zāļu ievadei un Aβ plāksnīšu kvantitatīvai analīzei smadzenēs AD peļu modelī. Tika novērots, ka pretiekaisuma viela auranofīns ievērojami samazināja Aβ patoloģiju. Sekojoši, tika optimizētas jaunas pieejas divām metodēm. Kopumā iegūtie dati par pretiekaisuma vielu auranofīnu un jaunu metožu attīstīšanu un pilnveidošana sniedz nozīmīgu pienesumu pirmsklīniskos pētījumos AD jomā. Atslēgas vārdi: Alcheimera slimība; transgēnās peles modulis; β-amiloīda patoloģija; auranofīns; intracerebrālā ievade; mini-osmotiskais sūknis; kanulas fiksācija; histopatoloģiskā kvantifikācija
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Currently, available symptomatic drug therapies do not cope with the progression of the disease. The delivery of the tested compounds to the brain may be challenging therefore mini-osmotic pumps represent a suitable delivery system for enhancing drug delivery across the BBB. The goal of this thesis was to evaluate the effects of an anti-inflammatory drug as well as to improve the methodology for intracerebral drug delivery and quantitative analysis of Aβ plaques in the brain of the AD mouse model. The findings of this thesis indicated that the administration of the anti-inflammatory drug auranofin significantly reduces Aβ pathology. Two novel experimental methods have been developed to perform stereotactic brain infusion experiments. To summarize, the data obtained on the effects of the anti-inflammatory drug and the newly developed methods enhance preclinical research in the AD field. Keywords: Alzheimer's disease; transgenic mouse model; amyloid-β; auranofin; intracerebral infusion; mini-osmotic pump; cannula fixation; histopathological quantification
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Currently, available symptomatic drug therapies do not cope with the progression of the disease. The delivery of the tested compounds to the brain may be challenging therefore mini-osmotic pumps represent a suitable delivery system for enhancing drug delivery across the BBB. The goal of this thesis was to evaluate the effects of an anti-inflammatory drug as well as to improve the methodology for intracerebral drug delivery and quantitative analysis of Aβ plaques in the brain of the AD mouse model. The findings of this thesis indicated that the administration of the anti-inflammatory drug auranofin significantly reduces Aβ pathology. Two novel experimental methods have been developed to perform stereotactic brain infusion experiments. To summarize, the data obtained on the effects of the anti-inflammatory drug and the newly developed methods enhance preclinical research in the AD field. Keywords: Alzheimer's disease; transgenic mouse model; amyloid-β; auranofin; intracerebral infusion; mini-osmotic pump; cannula fixation; histopathological quantification
Description
Elektroniskā versija nesatur pielikumus
Keywords
Medicīna un farmācija , Medicīna , Veselības aprūpe