Obilježja upale posredovane TLR2 receptorom nakon ishemijske lezije mišjeg mozga

doctoral thesis

• Title (english): Features of TLR2 receptor-mediated inflammation after ischemic lesion of mouse brain
• Author: Sanja Srakočić
• Mentor: Srećko Gajović (mentor)
• Committee member: Nataša Jovanov Milošević (predsjednik povjerenstva)
• Committee member: Vesna Lukinović-Škudar (član povjerenstva)
• Committee member: Fran Borovečki (član povjerenstva)
• Committee member: Nives Pećina-Šlaus (član povjerenstva)
• Committee member: Marija Renić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2023-09-04, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Cytology, Histology and Embryology
• Universal decimal classification (UDC): 611 - Anatomy

Abstract

Cilj ovog istraživanja bio je okarakterizirati upalu posredovanu receptorom TLR2 te korelirati izražaj gena Tlr2 s volumenom ishemijske lezije kod odraslih miševa.
Ishemijska lezija kod Wt(Tlr2-luc) i Tlr2-/-(Tlr2-luc) miševa bila je izazvana metodom tMCAO. Miševi su snimani MRI-em i BLI-em tijekom 7 dana nakon tMCAO kako bi se longitudinalno pratio razvoj ishemijske lezije te posljedični upalni odgovor. Rezultati snimanja upotpunjeni su procjenom neurološkog deficita, analizom upalnih biljega mikroglije te određivanjem razine citokina u krvnoj plazmi.
Aktivnost promotora gena Tlr2 određena in vivo bioluminiscencijom pokazala se kao odličan model za praćenje intenziteta upalnog odgovora nakon moždanog udara. Nedostatak receptora TLR2 uzrokovao je nastanak veće ishemijske lezije i izraženiji edem, ali nije utjecao na preživljenje, doveo je do bržeg smanjenja upalnog odgovora te je potaknuo brži neurološki oporavak. Nadalje, volumen ishemijske lezije je pokazao pozitivnu korelaciju s neurološkim deficitom i jačinom upale, neovisno o prisutnosti receptora TLR2. Nedostatak receptora TLR2 smanjio je izražaj upalnih biljega mikroglije, a u krvi su povećane razine pro-upalnih i anti-upalnih citokina, ukazujući na njegovu dvojaku ulogu.
Sveukupno gledajući, ovo istraživanje je pokazalo kako je nedostatak receptora TLR2 promijenio dinamiku upalnih procesa nakon ishemijske ozljede mozga te pospješio neurološki oporavak u akutnoj fazi moždanog udara kod miševa.

Abstract (english)

The aim of this study was to characterize TLR2-mediated inflammation and correlate Tlr2 gene expression with the volume of ischemic brain lesions in adult mice.
Ischemic lesions in Wt(Tlr2-luc) and Tlr2-/-(Tlr2-luc) mice were induced by the tMCAO method. Mice were imaged by MRI and BLI throughout 7 days after tMCAO to longitudinally monitor the progression of the ischemic lesion and the associated inflammation. Imaging results were complemented by neurological deficit assessment, analysis of microglial inflammation markers, and determining cytokine levels in blood plasma.
The activity of the Tlr2 gene promoter, monitored by in vivo bioluminescence, proved to be a great model for monitoring inflammation intensity following a brain stroke. TLR2 deficiency caused the formation of a larger ischemic lesion and increased edema; however, survival was not affected. Inflammation reduction was quicker with more prominent neurological recovery. Additionally, the volume of the ischemic lesion positively correlated with the neurological deficit and the inflammation intensity, regardless of TLR2 presence. TLR2 deficiency caused a reduction in inflammatory microglial markers and increased levels of pro-inflammatory and anti-inflammatory cytokines in blood, indicating its dual role.
Overall, this research showed that TLR2 deficiency changed the dynamics of inflammatory processes after ischemic brain injury and facilitated neurological recovery in the acute phase of brain ischemia in mice.

• Keywords: Citokini; Ishemija mozga; Moždani udar; Mozak; Upala; Magnetska rezonancija; Ishemija; Edem; Miševi
• Keywords (english): Cytokines; Brain Ischemia; Stroke; Brain; Inflammation; Magnetic Resonance Imaging; Ischemia; Edema; Mice
• Language: croatian
• URN:NBN: urn:nbn:hr:105:109244
• Project: Number: IP-2016-06-1892; Title: Multimodalni prikaz molekularnih zbivanja tijekom oporavka mišjeg mozga nakon ishemijskog oštećenja; Acronym: RepairStroke; Leader: Srećko Gajović; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Biomedicine and Health Sciences; 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: 165 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-09-07 10:48:49