Regionalno specifičan neuroprotektivan efekat progesterona u modelu hipoperfuzije mozga pacova

Abstract

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). Potential 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.