Dejstvo hiperbarične oksigenacije na regenerativni potencijal moždanog tkiva u eksperimentalnom modelu traumatske povrede mozga

Abstract

Traumatsko oštećenje mozga nastaje usled dejstva spoljašnje sile i predstavlja globalni zdravstveni problem, koji narušava zdravlje velikog broja ljudi. Zbog kompleksnosti događaja u tkivu nakon povrede i dalje se traga za adekvatnim terapijskim protokolima. U ovoj tezi ispitivan je uticaj hiperbarične oksigenacije (HBO) na regenerativne procese u kortikalnom tkivu koje okružuje mesto povrede i na proces adultne neurogeneze u neurogenim zonama mozga adultnih pacova nakon ablacije desnog senzomotornog korteksa (ASK). Urađena su odgovarajuća imunohistohemijska i imunofluorescentna bojenja, analiza genske ekspresije i imunoblot analize. ASK stimuliše stvaranje glijalnog ožiljka i polarizaciju mikroglije i astrocita ka proinflamatornom fenotipu. Deset HBO tretmana nakon ASK smanjuje gliozu i stimuliše polarizaciju mikroglije i astrocita ka antiinflamatornom fenotipu. Korišćeni HBO tretman stimuliše adultnu neurogenezu oko mesta lezije i u subventikularnoj zoni (SVZ). HBO smanjenjem neuroinflamacije stimuliše migraciju neuroblasta iz SVZ i rostralnog migratornog puta ka mestu lezije i ubrzava njihovu maturaciju. Dodatno, HBO tretman stimuliše stvaranje progenitora neurona oko mesta povrede. ASK pokazuje specifičan uticaj na zubatu vijugu (DG) uzrokujući ćelijsku smrt neurona u subgranularnoj zoni (SGZ), kao i u unutrašnjoj i srednjoj trećini granularnog sloja DG hipokampusa. HBO tretman smanjuje osetljivost zrelih neurona granularnog sloja DG na ASK. Takođe, HBO tretman sprečava gubitak novonastalih nezrelih neurona u SGZ i sprečava degeneraciju njihovih dendrita. Dok ASK smanjuje broj ćelija koje proliferišu u SGZ, HBO tretman nakon povrede povec ava broj ovih c elija. Ovakvi rezultati ukazuju na moguću upotrebu HBO kao adjuvantnog tretmana u lečenju povreda mozga.

Traumatic brain injury is the results of external impact and is a global health problem that affects the health of many people. Due to the complexity of the events in the tissue after the injury, appropriate therapeutic protocols are still lacking. In this study, the influence of hyperbaric oxygenation (HBO) on the regeneration processes in the cortical tissue around the lesion site and on the process of adult neurogenesis in the neurogenic zones of the adult rat brain after ablation of the right sensorimotor cortex (SCA) was investigated. Appropriate immunohistochemical and immunofluorescent staining, gene expression, and immunoblot analysis were performed. SCA stimulates glial scar formation and polarization of microglia and astrocytes toward a proinflammatory phenotype. Ten HBO treatments after SCA reduce gliosis and stimulate polarization of microglia and astrocytes towards an anti-inflammatory phenotype. HBO treatment stimulates adult neurogenesis around the lesion site and in the subventricular zone (SVZ). By reducing neuroinflammation, HBO stimulates the migration of neuroblasts from the SVZ and rostral migratory stream to the lesion site and accelerates their maturation. In addition, HBO treatment stimulates the formation of neuronal progenitor cells around the injury site. SCA shows a specific effect on the dentate gyrus (DG), causing cell death of neurons in the subgranular zone (SGZ) and in the inner and middle third of the granular layer of the DG hippocampus. HBO treatment reduces the vulnerability of mature neurons in the granular layer of the DG to SCA. Moreover, HBO treatment prevents the loss of newly formed immature neurons in the SGZ and the degeneration of their dendrites. At the same time, SCA reduces the number of proliferating cells in the SGZ, and HBO treatment after injury increases the number of these cells. These results justify the use of HBO as an adjuvant treatment for brain injury.