Bradikininski receptori u ishemijskom moždanom udaru

master's thesis

• Title (english): Bradykinin receptors in ischemic stroke
• Author: Nika Filipović
• Mentor: Marina Radmilović (mentor)
• Committee member: Aleksandra Dugandžić (predsjednik povjerenstva)
• Committee member: Dinko Mitrečić (član povjerenstva)
• Committee member: Marina Radmilović (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Histology and Embryology); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Cytology, Histology and Embryology

Abstract

Moždani udar je u razvijenim zemljama treći po učestalosti uzrok smrti i vodeći uzrok invalidnosti. Svake godine približno 800 000 ljudi doživi moždani udar, bilo da je riječ o prvom ili o rekurentnom moždanom udaru. Jedina terapija koja se primijenjuje kod pacijenata s moždanim udarom je fibrinoliza, koja je opcija za ograničen broj pacijenata. U ishemijskom moždanom udaru je kalikrein-kinin sustav jedan od prvih upalnih puteva koji se aktivira nakon oštećenja tkiva. Tijekom ishemije značajno se povećava koncentracija bradikinina kao i izražaj bradikininskih receptora. Jedan od najvažnijih i najčešće zabilježenih učinaka bradikinina u ishemijskom moždanom udaru je učinak na permeabilnost krvno-moždane barijere. Bradikinin, povećavajući vaskularnu permeabilnost i vazodilataciju, povećava moždani edem i na taj način značajno pogoršava ishemijsko oštećenje. Mikroglija i astrociti su glija stanice koje imaju brojne ulogu u razvoju ishemijskog moždanog udara te u interakciji s bradikininom ostvaruju različite upalne, ali i protuupalne učinke. S jedne strane bradikinin potiče lučenje citokina i kemokina, djeluje kao kemoatraktant leukocita, potiče adheziju trombocita te pojačava oštećenje, dok s druge strane inhibira proizvodnju proupalnih citokina, potiče migraciju reparativnih stanica do mjesta ozljede te sudjeluje u popravku i regeneraciji nastalog ishemijskog oštećenja. Kalikrein, stvaranjem kinina, inducira angiogenezu, neovaskularizaciju te obnavlja poremećeni krvni moždani protok. Također, kalikrein smanjuje ishemijski induciranu apoptozu i oksidacijski stres. Zaključno možemo reći da aktivacija bradikininskih receptora u ishemijskom moždanom udaru uzrokuje različite štetne, ali i protektivne učinke ovisne o vremenu proteklom od nastanka ishemije i stupnju ishemije.

Abstract (english)

Stroke is the third leading cause of death and the leading cause of disability in the Western world. Every year approximately 800,000 people experience stroke, whether it is the primary or recurrent stroke. Today, fibrinolysis is the only therapy applied in stroke patients, which is an option for a limited number of patients. In ischemic stroke, the kinin-kallikrein system is one of the first inflammatory pathways activated after ischemic tissue damage. Bradykinin concentrations as well bradykinin receptors expression significantly rise during stroke. One of the most important and most commonly reported effects of bradykinin in ischemic stroke is its effect on blood-brain barrier vascular permeability. Bradykinin expands the size of cerebral edema by increasing vascular permeability and vasodilation, significantly exacerbating the ischemic damage. Microglia and astrocytes play a significant role in the development of ischemic stroke. Their interaction with bradykinin cause various inflammatory and antiinflammatory effects. Bradykinin stimulates cytokine and chemokine secretion, acts as a leukocyte chemoattractant, promotes platelet adhesion and exacerbates inflammatory damage, but also inhibits the production of proinflammatory cytokines, stimulates migration of repair cells to the site of injury and participates in repair and regeneration of the ischemic damage. Kallikrein, forming kinins, induces angiogenesis, neovascularization and regenerates the disturbed blood flow. Moreover, kallikrein reduces ischemically induced apoptosis and oxidative stress. In conclusion, the activation of bradykinin receptors in ischemic stroke causes various deleterious but also neuroprotective effects, primarily depending on the time elapsed since the onset of ischemia and the degree of ischemia.

• Keywords: bradikinin; ishemijski moždani udar; edem mozga; angiogeneza
• Keywords (english): bradykinin; ischemic stroke; brain edema; angiogenesis
• Language: croatian
• URN:NBN: urn:nbn:hr:105:215183
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-03-02 15:54:16