Abstract
Cerebral ischemic stroke is regarded as one of the most serious diseases in the human central nervous system. The secondary ischemia and reperfusion (I/R) injury increased the difficulty of treatment. Moreover, the latent molecular regulating mechanism in I/R injury is still unclear. Based on our previous clinical study, we discovered that FK506 binding protein 5 (FKBP5) is significantly upregulated in patients, who suffered acute ischemic stroke (AIS), with high diagnostic value. Levels of FKBP5 were positively correlated with patients’ neurological impairments. Furthermore, a transient middle cerebral artery occlusion (tMCAO) model of mice was used to confirm that FKBP5 expression in plasma could reflect its relative level in brain tissue. Thus, we hypothesized that FKBP5 participated in the regulation of cerebral I/R injury. In order to explore the possible roles FKBP5 acted, the oxygen and glucose deprivation and reoxygenation (OGD/R) model was established to mimic I/R injury in vitro. FKBP5 expressing levels were changed by plasmid stable transfection. The altered expression of FKBP5 influenced cell viability and autophagy after OGD/R injury notably. Besides, AKT/FOXO3 cascade was involved in the FKBP5-regulating process. In the present study, FKBP5 was verified upregulated in cerebral I/R injury, related to the severity of ischemia and reperfusion injury. Additionally, our analyses revealed that FKBP5 regulates autophagy induced by OGD/R via the downstream AKT/FOXO3 signaling pathway. Our findings provide a novel biomarker for the early diagnosis of ischemic stroke and a potential strategy for treatment.
Highlights
Cerebral ischemic stroke is a common neurological disease involving a loss of focal brain function, paralysis or numbness of the limbs, and aphasia (Zerna et al, 2018)
To determine whether FK506 binding protein 5 (FKBP5) is involved in ischemic stroke, we examined its expression in patients with acute ischemic stroke (AIS)
Both quantitative real-time PCR and enzyme-linked immunosorbent assays (ELISA) indicated that plasma FKBP5 expression is higher in AIS patients than healthy individuals (Figures 1A,B)
Summary
Cerebral ischemic stroke is a common neurological disease involving a loss of focal brain function, paralysis or numbness of the limbs, and aphasia (Zerna et al, 2018). Ischemia and reperfusion (I/R) injury in the penumbra area makes the treatment of cerebral ischemic stroke difficult (Powers et al, 2018). Autophagy is a process of dynamic changes, which can play either protective or destructive roles. It is often regarded as a ‘‘doubleedged sword.’’ It has been reported that autophagy is involved in the pathogenesis of ischemic stroke including apoptosis, oxidative stress, inflammation, and energy reduction (Wang et al, 2018). Autophagy, which is induced by the I/R injury, can activate astrocytes to regulate normal functions of the brain through interacting with parenchymal cells (Dong et al, 2016; Han et al, 2018).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
