Regionalno specifičan neuroprotektivan efekat progesterona u modelu hipoperfuzije mozga pacova
Regionally specific neuroprotective effect of progesterone in rat cerebral hypoperfusion model
Author
Guševac Stojanović, IvanaMentor
Drakulić, DunjaCommittee members
Nedeljković, NadeždaMartinović, Jelena
Metadata
Show full item recordAbstract
Pro-oksidativne i pro-apoptotske promene biomolekula, uključujući lipide, proteine i DNK, koje
nastaju usled smanjenja protoka krvi kroz mozak (moždana hipoperfuzija, MH) za posledicu mogu
imati narušavanje strukture i funkcije ćelija prečeone moždane kore i hipokampusa. Do sada je
testiran efekat brojnih jedinjenja kako bi se ublažile posledice MH, ali adekvatna terapija još uvek
ne postoji. Steroidni hormon progesteron (P4) se nametnuo kao tretman u brojnim modelima
neuroloških bolesti, jer smanjuje otok mozga, povećava motorne i kognitivne sposobnosti i drugo,
koje nastaju usled oksidativnog/nitrozativnog stresa (OS/NS), prevazilaženja kapaciteta antioksidativne
(AO) zaštite i apoptoze.
Za potrebe proučavanja efekata P4 u stanju eksperimentalno izazvane trajne MH, odrasli mužjaci
pacova Wistar soja podeljeni su u tri grupe: lažno operisane jedinke injecirane lanenim uljem
(1 mg/kg/7 dana, kontrole), jedinke sa podvezanim karotidnim arterijama injecirane lanenim uljem
(1 mg/kg/7 dana...) ili P4 (1.7 mg/kg/7 dana). Potencijalne promene su praćene pomoću
odgovarajućih testova ponašanja, biohemijskih i histoloških metoda.
Analiza ispitivanih parametara ukazuje na to da je P4 sposoban da ublaži MH-izazvane poremećaje
ponašanja, smanji obim ćelijske smrti i održi „normalnu“ morfologiju ćelija uočenu kod kontrola,
kao i da regionalno-specifično moduliše indikatore OS/NS, pospeši AO i anti-apoptotsku odbranu
delovanjem na enzimsku aktivnost, gensku i proteinsku ekspresiju. Predstavljeni rezultati mogu
pružiti bazu za dalja ispitivanja koja bi upotpunila saznanja o efektima P4 u MH i sličnim
povredama mozga.
Pro-oxidative and pro-apoptotic modifications of biomolecules, including lipids, proteins and DNA,
due to cerebral blood flow restriction (cerebral hypoperfusion, MH) may induce structural and
functional alterations of prefrontal cortex and hippocampus cells. To date, the effect of a numerous
compounds has been tested to mitigate the outcomes of MH, but adequate therapy does not yet
exist. Steroid hormone progesterone (P4) has been used as a treatment in many neurological models
since it reduces brain swelling, increases motor and cognitive abilities, etc, arised due to
oxidative/nitrosative stress (OS/NS), deteriorated anti-oxidative (AO) capacity and apoptosis.
To study the effects of P4 in experimentally induced permanent MH, adult male Wistar rats were
divided into three groups: sham operated animals injected with flaxseed oil (1 mg/kg/7 days,
controls), animals with permanently occluded carotid arteries treated either with flaxseed oil
(1 mg/kg/7 days) or P4 (1.7 mg/kg/7 days). Po...tential changes were monitored using appropriate
behavioural tests, biochemical and histological methods.
The obtained results indicate that P4 is capable to ameliorate MH-induced behavioural disorders,
reduce the extent of cell death and maintain "normal" cell morphology as observed in controls, as
well as to modulate the action of tested OS/NS indicators, enhance AO and anti-apoptotic defence
by acting on enzymatic activity, gene and protein expression in regional specific manner. Herein
presented findings could provide a basis for further studies that would fulfill the knowledge of P4
outcomes in MH and similar brain insults.
Faculty:
Универзитет у Београду, Биолошки факултетDate:
29-09-2020Projects:
- Cellular and molecular basis of neuroinflamation: potential targets for translational medicine and therapy (RS-41014)
- Molecular mechanisms of cellular responses on pathological changes in central neuronal system and peripheral organs of mammals (RS-173044)