Role of perivascular macrophages in cerebral aneurysm formation and rupture in a new model of middle cerebral artery aneurysm

master's thesis

• Title (croatian): Uloga perivaskularnih makrofaga u formiranju i rupturi cerebralnih aneurizmi u novom modelu aneurizme srenje moždane arterije
• Author: Ana Jelić
• Mentor: Vladimir Mrša (mentor)
• Committee member: Vladimir Mrša (predsjednik povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Biochemistry); Zagreb
• Defense date and country: 2022-07-11, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Cerebral aneurysms are pathological dilatations of the brain arteries characterized by the degeneration and the weakening of the vessel wall that can eventually lead to its rupture. Rupture of cerebral aneurysms is a leading cause of subarachnoid haemorrhage that results in high mortality, while a majority of survived patients suffer permanent and severe neurocognitive disabilities. Evidence suggests that inflammation may play a significant role in the pathogenesis of cerebral aneurysms. Perivascular macrophages (PVMs) are found to actively participate in the inflammatory response, pointing out their role in the inflammatory response upon aneurysm pathology. The first aim of this project was to validate a new model of aneurysm in the middle cerebral artery (MCA) area by the examination of the morphological and inflammatory features of aneurysms. Our results show that these aneurysms showed morphological changes in the vessel wall, increased microglial activation in the area surrounding the aneurysm, as well as accumulation of inflammatory cells (neutrophils and T-cells), similar to the human pathology. The second aim of this study was to determine the role of PVMs which were found around the aneurysms in our model. To do this, PVMs were depleted by the intracerebroventricular injection of clodronate liposomes. The depletion reduced the number of developed aneurysms and neutrophil infiltration around the aneurysms. These results suggest the involvement of PVMs in cerebral aneurysm formation, progression, and rupture.

Abstract (croatian)

Cerebralne aneurizme su patološka proširenja cerebralnih arterija koje karakterizira degeneracija i slabljenje stijenke krvne žile koji mogu dovesti do njezina puknuća. Ruptura cerebralnih aneurizmi vodeći je uzrok subarahnoidalnog krvarenja koje rezultira visokom smrtnošću, dok većina preživjelih pacijenata pati od teških neurokognitivnih oštećenja. Poznato je da upalna reakcija ima značajnu ulogu u patologiji cerebralnih aneurizmi. Također je poznato da perivaskularni makrofagi (PVM) aktivno sudjeluju u upalnom odgovoru, ukazujući na njihovu potencijalu ulogu u ovoj patologiji. Prvi cilj ovog projekta bio je utvrditi je li novi model aneurizme u području srednje moždane arterije prema morfološkim i upalnim karakteristikama relevantan za istraživanje ljudskih aneurizmi. Slično ljudskim aneurizmama, aneurizme u ovom modelu pokazale su morfološke promjene u stijenci krvnih žila, povećanu mikroglijalnu aktivaciju u području oko aneurizme, kao i nakupljanje upalnih stanica (neutrofila i T-stanica). Sljedeći cilj ovog istraživanja bilo je utvrditi ulogu perivaskularnih makrofaga, pronađenih oko aneurizmi u našem modelu. Kako bi se to postiglo, perivaskularni su makrofagi uklonjeni intracerebroventrikularnom injekcijom liposoma koji sadrže klodronat. Njihovim uklanjanjem smanjio je broj razvijenih aneurizmi, ali i infiltraciju neutrofila oko aneurizmi. Ovi rezultati sugeriraju na ulogu perivaskularnih makrofaga u formiranju, razvoju i rupturi cerebralnih aneurizmi.

• Keywords: Cerebral aneurysm; inflammation; neutrophils; perivascular macrophages; vessel wall
• Keywords (croatian): cerebralne aneurizme; upala; neutrofili; perivaskularni makrofagi; stijenka krvne žile
• Language: english
• URN:NBN: urn:nbn:hr:159:366717
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2024-04-29 09:21:32