Glikojenin İskemik İnme ve Retinal İskemi Üzerine Olan Etkilerinin Nörogliovasküler Seviyede İncelenmesi

Abstract

Ischemic stroke results in sudden blood flow cessation thus leads to sudden onset unmet energy requirements. Although the clotted artery is recanalized and blood flow is restored back, brain perfusion may not be sustained due to pericyte contraction. Under glucose deprived and hypoxic conditions, glucose derived from the glycogen stored around peri-microvascular astrocyte endfeets may serve as emergency fuel to meet metabolic demand during acute period of ischemic stroke. These mechanicsm should be investigated in retina, because retina is known as an extension of central nervous system and has highest number of pericyte among other tissues. Effects of intracerebroventricularly and intravitreally administered glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) are investigated through several time points. Moreover, transgenic mice in which glycogen synthase-1 expression is knocked out throughout its central nervous system (GYS-1NestinKO) are used in this study. These models demonstrates ischemic-like phenotype and microvascular constrictions under normal circumstances. When ischemia is introduced to glycogen utilization distruped mice, infarct volumes are increased compared to wild type littermates. Increased number of retinal microvascular constrictions contralaterally after ischemia in transgenic and wild type and intravitreally DAB injected mice are observed first time. Interaction of glycogen and microvascular constrictions are shown with both Periodic acid Schiff (PAS) and immunofluorescent anti-glycogen antibodies. In addition, important cellular alterations regarding blood-brain/retina barrier are observed. Number of PDGFR-β positive pericytes becomes less and detaches from their respective microvascular wall while NG2 and CD13 expressing pericytes seemes unaffected among these mice. Claudin-5 and GLUT-1 levels decline despite comparable preservation of ZO-1 and AQP4. Revealing impact of glycogen at neurogliovascular level in both brain and retina may become crucial for understanding the pathophysiology of ischemic stroke and retinal diseases together with the possible use of more effective therapeutic approaches of stroke.