Anesthetic Preconditioning Inhibits Isoflurane-Mediated Apoptosis in the Developing Rat Brain

Abstract

Background We hypothesized that preconditioning with a short exposure to isoflurane (ISO) would reduce neurodegeneration induced by prolonged exposure to ISO in neonatal rats, as previously shown in neuronal cell culture. Methods We randomly divided 7-day-old Sprague-Dawley rats into 3 groups: control, 1.5% ISO, and preconditioning (PC) + 1.5% ISO. The control group was exposed to carrier gas (30% oxygen balanced in nitrogen) for 30 min and then carrier gas again for 6 h the following day. The 1.5% ISO group was exposed to carrier gas for 30 min and then 1.5% ISO for 6 h the following day. The PC + 1.5% ISO group was preconditioned with a 30 min 1.5% ISO exposure and then exposed to 1.5% ISO for 6 h the following day. Blood and brain samples were collected 2 h after the exposures for determination of neurodegenerative biomarkers, including caspase-3, S100β, caspase-12, and an autophagy biomarker Beclin-1. Results Prolonged exposure to ISO significantly increased cleaved caspase-3 expression in the cerebral cortex of 7-day old rats compared to the group preconditioned with ISO and the controls using Western blot assays. However, significant differences were not detected for other markers of neuronal injury. Conclusion The ISO-mediated increase in cleaved caspase-3 in the postnatal day 7 rat brain is ameliorated by preconditioning with a brief anesthetic exposure, and differences were not detected in other markers of neuronal injury.

Propofol Affects Neurodegeneration and Neurogenesis by Regulation of AutophagyviaEffects on Intracellular Calcium Homeostasis

“…Most of the previous studies have focused on the anesthetic-induced type 1 cell death (apoptosis), 21,22 but cells can also die from type 2 (autophagic cell death) or type 3 cell death (necrosis). Palanisamy et al 23 recently demonstrated that propofol, at approximately 15 and 30 μM, for a 4 h exposure, did not induce rat primary NPC necrotic cell death and apoptosis.…”

Bone-marrow mesenchymal stem-cell administration significantly improves outcome after retinal ischemia in rats

“…The mechanisms of attenuation of the blood-retinal barrier by BMSCs were not determined in the present study. However, some stem cells have been found to produce genes mediating barrier properties [40], and adipose-derived stem cells prevented blood-retinal barrier leakage in diabetic rats possibly via differentiation into glial cells [41]. …”

Anesthetic neurotoxicity: Apoptosis and autophagic cell death mediated by calcium dysregulation

“…Zhou et al showed that sevoflurane induced ER stress and activated autophagy, which protected against sevoflurane-induced apoptosis in H4 cells (Zhou et al, 2016). It also been suggested that isoflurane-induced increase in cleaved caspase-3 in the neonatal rat brain can be ameliorated by preconditioning with a brief anesthetic exposure (Peng et al, 2014). Consistent with these findings, it was proposed that adequate promotion of autophagy may play a protective role for cell survival by preventing developmental neurotoxicity of general anesthetics (Li and Yu, 2014).…”