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2012, vol. 62, br. 4, str. 385-401
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Metabolizam biogenih amina u akutnoj ishemiji mozga - uticaj sistemske hiperglikemije
Metabolism of biogenic amines in acute cerebral ischemia: Influence of systemic hyperglycemia
aUniverzitet u Beogradu, Medicinski fakultet, Institut za medicinu rada i radiološku zaštitu 'Dr Dragomir Karajović' bKlinički centar Srbije, Beograd cUniverzitet u Beogradu, Medicinski fakultet, Institut za rehabilitaciju 'Dr M. Zotović' dHigh Health School of Professional Studies, Belgrade
e-adresa: milalex@eunet.rs
Sažetak
Efekat ishemije na parenhim mozga zavisi od mnogih faktora, kao što su mehanizam nastalog prekida protoka krvi, brzina nastalog prekida protoka krvi, dužina trajanja ishemične epizode, organizacija anatomskih struktura krvnih sudova mozga itd., što sve utiče na krajnji ishod. Dopamin, noradrenalin i serotonin su biogenic amini koji se ubrajaju u transmitere centralnog nervnog sistema. Pri prekidu moždane cirkulacije u eksperimentalnim ili kliničkim uslovima metabolizam neurotransmitera, u prvom redu biogenih amina, je poremećen. Mnoga istraživanja na raznim eksperimentalnim modelima kompletne ishemije ukazuju na smanjenje sadržaja noradrenalina, dopamina i serotonina u centralnim nervnim tkivima. Dokazano je da hiperglikemija može drastično da poveća cerebralno oštećenje praćeno kratkotrajnom cerebralnom ishemijom. Imajući u vidu činjenicu da biogeni amini (dopamin, noradrenalin i serotonin) neposredno učestvuju u određivanju veličine neurološkog oštećenja i činjenicu da je u stanjima hiperglikemije veličina infarkta (sa morfološkog aspekta) veća u odnosu na normoglikemičnu situaciju, hteli smo da proverimo kolika je uloga biogenih amina u nastajanju oštećenja u stanjima hiperglikemije, odnosno u situacijama pojave apopleksije mozga u dijabetičara. Analizom metabolizma biogenih amina u stanjima akutne i hronične hiperglikemije i efekat reberzibilne i ireverzibilne ishemije mozga na metabolizam serotonina, dopamina i noradrenalina, ustanovljeno je da akutna hipeglikemija usporava metabolizam serotinana, dopamina i noradrenalina u kori mozga i n. caudatus-u. Ishemija mozga u normoglikemičnih životinja po sebi je bez uticaja na metabolizam biogenih amina, ali se efekat ishemije ispoljava u toku recirkulacije. U recirkulaciji, što odgovara događajima u penumbri, oslobađanje biogenih amina je nekontrolisano i pojačano. Ishemija mozga u akutno-hipeglikemičnih životinja povećava oslobađanje biogenih amina nezavisno od dužine trajanja ishemije (5 ili 15 minuta). Ovaj efekat je još više izražen tokom recirkulacije. Akutna hiperglikemija čini moždano tkivo osetljivim već na ishemiju kraćeg trajanja - reverzibilnu ishemiju.
Abstract
Dopamine, norepinephrine and serotonin are biogenic amines which are transmitters of the central nervous system. The effects of ischemia on the brain parenchyma depends on many factors, such is the mechanism of blood flow interruption, velocity of the occurring blood flow interruption, duration of an ischemic episode, organization of anatomical structures of the brain blood vessels etc., which all influence the final outcome. During interruption of the brain circulation in experimental or clinical conditions, neurotransmitter metabolism, primarily of biogenic amines, is disturbed. Many researches with various experimental models of complete ischemia reported a decrease in the content of norepinephrine, dopamine and serotonin in the CNS tissue. It was proven that hyperglycemia can drastically increase cerebral injury followed by short-term cerebral ischemia. Considering the fact that biogenic amines (dopamine, norepinephrine and serotonin) influence the size of neurologic damage, as well as the fact that in hyperglycemic conditions infarct size (from the morphological aspect) is larger relative to normoglycemic status, the intention was to evaluate the role of biogenic amines in occurrence of damage in conditions of hyperglycemia, i.e. in the case of brain apoplexia in diabetics. Analysis of biogenic amines metabolism in states of acute hyperglycemia, as well as analysis of the effects of reversible and irreversible brain ischemia on metabolism of serotonin, dopamine and norepinephrine, showed that acute hyperglycemia slows down serotonin, dopamine and norepinephrine metabolism in the cerebral cortex and n. caudatus. Brain ischemia in normoglycemic animals by itself has no influence on biogenic amines metabolism, but the effect of ischemia becomes apparent during reperfusion. In recirculation, which corresponds to the occurrences in penumbra, release of biogenic amines is uncontrolled and increased. Brain ischemia in acute hyperglycemic animals increases the release of biogenic amines regardless of ischemia duration (5 or 15 minutes). This effect is more apparent during recirculation. Acute hyperglycemia makes brain tissue more sensitive even to ischemia which last shorter, i.e. reversible ischemia.
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