Circular RNA cerebellar degeneration-related protein 1 antisense RNA (Circ-CDR1as) downregulation induced by dexmedetomidine treatment protects hippocampal neurons against hypoxia/reoxygenation injury through the microRNA-28-3p (miR-28-3p)/tumor necrosis factor receptor-associated factor-3 (TRAF3) axis

Abstract

Cerebral ischemia/reperfusion (CI/R) injury results in serious brain tissue damage, thereby leading to long-term disability and mortality. It has been reported that dexmedetomidine (DEX) exerted neuroprotective effects in CI/R injury. Herein, we intended to investigate whether and how circular RNA (circRNA) cerebellar degeneration-related protein 1 antisense RNA (circ-CDR1as) was involved in the DEX-mediated protection on hippocampal neurons. In our work, the mouse hippocampal neuronal cells (HT-22) were used to construct a hypoxia/reperfusion (H/R) model for CI/R injury. Cell proliferation and apoptosis were evaluated by CCK-8 and flow cytometry. Gene expressions were detected by RT-qPCR. Levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) were measured by ELISA. The association between miR-28-3p and circ-CDR1as or TRAF3 was verified by dual-luciferase assay. The results indicated that DEX alleviated HT-22 cell dysfunction induced by H/R treatment. In addition, circ-CDR1as was downregulated after DEX treatment and reversed the effects of DEX on the proliferation, apoptosis, and inflammatory responses of H/R-treated HT-22 cells. Circ-CDR1as positively regulated TRAF3 expression via interaction with miR-28-3p in HT-22 cells. Circ-CDR1as aggravated H/R-treated HT-22 cell dysfunction through targeting miR-28-3p. Furthermore, TRAF3 inhibition partly abolished the effect of circ-CDR1as overexpression on cellular activities of H/R-treated HT-22 cells. To sum up, our findings, for the first time, demonstrated that DEX exerted neuroprotective effects on hippocampal neurons against H/R treatment via the circ-CDR1as/miR-28-3p/TRAF3 regulatory network, providing novel therapeutic targets for DEX administration in CI/R treatment.

Dexmedetomidine alleviates high glucose-induced podocyte damage by inhibiting EDA2R

“…EDA2R is a member of TNFR family whose signals are transduced by the TNFR-associated factors (TRAFs). A recent study reported that Dex treatment enhanced H/R-induced increase in TRAF3 expression in HT-22 cells [18], suggesting a possible regulative effect of Dex on the TNFR. Here, the results showed that overexpression of EDA2R reversed Dex-induced the alleviation in cell viability, apoptosis, EMT, as well as the albumin permeability in HG-stimulated podocytes.…”

Isoflurane enhances autophagy by activating AMPK/ULK1, inhibits NLRP3, and reduces cognitive impairment after cerebral ischemia-reperfusion injury in rats

“…Since Cerebral ischemia-reperfusion injury (CIRI) can cause severe brain tissue damage, it is an important factor leading to poor prognosis such as disability or death in patients with ischemic stroke (Wang and Wang, et al, 2021), therefore, it is particularly important to explore treatments that can effectively promote the recovery of patients. Iso urane is a safe and reliable inhalation anesthetic gas.…”

LncRNAs and CircRNAs as Strategies against Pathological Conditions Caused by a Hypoxic/Anoxic State

“…This article demonstrated that DEX relieved the H/R-induced apoptosis and inflammatory responses in HT-22 cells via the circ-CDR1as/miR-28-3p/TRAF3 cascade. In fact, upregulated circ-CDR1as reversed the protective effects of DEX [167] (Table 6 and Figure 3). These studies demonstrated the involvement of circRNAs in cerebral hypoxia and ischemic injuries.…”