Uloga bradikininskog receptora tipa 2 u razvoju ishemijske ozljede mozga i mrežnice

doctoral thesis

• Title (english): The role of bradykinin receptor type 2 in the development of brain and retinal ischemic lesion
• Author: Helena Justić
• Mentor: Marina Radmilović (mentor)
• Committee member: Nives Pećina-Šlaus (predsjednik povjerenstva)
• Committee member: Tomislav Jukić (član povjerenstva)
• Committee member: Aleksandra Dugandžić (član povjerenstva)
• Committee member: Hrvoje Banfić (član povjerenstva)
• Committee member: Nataša Jovanov Milošević (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2024-03-27, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Usprkos velikom broju kliničkih i pretkliničkih dokaza o korelaciji ishemije mozga i mrežnice, malo je pažnje posvećeno zajedničkim patološkim mehanizmima razvoja ishemijske ozljede istih. Cilj ovog istraživanja bio je longitudinalnim in vivo praćenjem razjasniti ulogu bradikininskog receptora tipa 2 u razvoju ishemijske ozljede mozga i mrežnice te odrediti primjenjivost in vivo snimanja mrežnične vaskulature za određivanje cerebrovaskularnih promjena u mišjem modelu moždanog udara. Usporedbom Koizumi i Longa zahvata okluzije srednje moždane arterije i dugotrajnim praćenjem statusa cerebralne vaskularne perfuzije magnetskom rezonancijom pokazano je da kod Koizumi zahvata ishemiju prati kronična hipoperfuzija i ishemija mozga i mrežnice, za razliku od Longa zahvata, u kojem nakon ishemije nastupa potpuna reperfuzija koja rezultira izraženijom cerebralnom atrofijom bez znakova oštećenja mrežnice. Usporedbom miševa s onemogućenim genom za bradikininski receptor tipa 2 te njihovih kontrola nakon Koizumi zahvata, dugotrajnim praćenjem razvoja ishemije magnetskom rezonancijom, fotografijom i fluoresceinskom angiografijom očne pozadine, testovima ponašanja i mjerenjem vaskularne propusnosti pokazano je da nedostatak bradikininskog receptora tipa 2 u akutnoj fazi ishemije smanjuje oštećenje i propusnost cerebralne vaskulature, a kronično povećava atrofiju moždanog tkiva i funkcionalni deficit. U mrežnici je pokazano slično djelovanje, odnosno povećanje vaskularne propusnosti u subakutnoj fazi, te povećanje ishemijskog oštećenja u kroničnoj fazi ishemije.

Abstract (english)

Despite ample clinical and preclinical evidence correlating cerebral and retinal ischemia, not enough attention has been paid to common pathological mechanisms of ischemic lesion development in these tissues. This research aimed to clarify the role of bradykinin receptor type 2 in the development of brain and retinal ischemia and to examine the applicability of in vivo retinal vascular imaging to determine cerebrovascular changes in a murine model of stroke. Comparing the Koizumi and Longa middle cerebral artery occlusion procedures by long-term cerebrovascular perfusion monitoring with magnetic resonance imaging showed that ischemia was followed by chronic hypoperfusion in both brain and retina in the Koizumi model. In contrast, complete reperfusion occurred in the Longa model, resulting in greater cerebral atrophy without retinal damage. By comparing bradykinin receptor type 2 knock-out mice and their controls after the Koizumi procedure using long-term monitoring with magnetic resonance, fundus photography, fluorescein angiography, behavioral tests and vascular permeability measurements, bradykinin receptor type 2 deficiency has been shown to reduce acute cerebral vascular permeability, while increasing cerebral atrophy and functional deficit in the chronic phase. Retinal findings showed a similar effect, increased subacute vascular permeability and increased ischemic damage in the chronic phase of ischemia.

• Keywords: Životinje; Miševi; Infarkt; srednja moždana arterija; Fluoresceinska angiografija; Propusnost kapilara; Modeli bolesti; Mozak; Mrežnica; Magnetska rezonancija; Perfuzija; Receptori; bradikinin; Spektroskopija magnetske rezonancije; Atrofija
• Keywords (english): Animals; Mice; Infarction; Middle Cerebral Artery; Fluorescein Angiography; Capillary Permeability; Disease Models; Brain; Retina; Magnetic Resonance Imaging; Perfusion; Receptors; Bradykinin; Magnetic Resonance Spectroscopy; Atrophy
• Language: croatian
• URN:NBN: urn:nbn:hr:105:824633
• Project: Number: UIP-2017-05-8082; Title: Uloga bradikinina u ishemiji mozga i mrežnice u mišjim modelima dijabetesa; Title: The role of bradykinin in brain and retinal ischemia in diabetic murine models; Acronym: BRADISCHEMIA; Leader: Marina Radmilović; Jurisdiction: Croatia; Funder: Hrvatska zaklada za znanost; Funding stream: Installation Research Projects
• Study programme: Title: Neuroscience; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 155 str.
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-03-28
• Created on: 2024-04-26 07:18:41