RESUMO
To assess the effectiveness and molecular mechanisms of mild hypothermia and remote ischemic postconditioning (RIPC) in patients with acute ischemic stroke (AIS) who have undergone thrombolysis therapy. A total of 58 AIS patients who received recombinant tissue plasmin activator (rt-PA) intravenous thrombolysis were included in this prospective study. Participants were randomly allocated to the experimental group (rt-PA intravenous thrombolysis plus mild hypothermic ice cap plus remote ischemic brain protection, n = 30) and the control group (rt-PA intravenous thrombolysis plus 0.9% saline, n = 28). The RIPC was performed for 14 consecutive days on both upper limb arteries spaced 2 minutes apart. Five cycles of ischemia-reperfusion were performed sequentially (2-2, 3-3, 4-4, 5-5, 5-0 minutes, respectively). The outcome measures of the National Institute of Health stroke scale (NIHSS) score, volume of cerebral infarction, serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1ß, tumor necrosis factor α, nuclear factors kappa B (NF-κB), and NOD-1ike receptor pyrin 3 (NLRP3) were evaluated at different time points after treatment. Similarly, the 90-day modified Rankin Scale (mRS) scores were compared between the two groups. After treatment, the NIHSS score, MDA, NF-κB, and NLRP3 levels in the experimental group were significantly lower than those in the control group (p < 0.05). While the SOD in the experimental group was significantly higher than in the control group (p < 0.05), the NIHSS scores decreased within groups (all p < 0.05) in both experimental and control groups. The 90-day mRS score (0-2 points) in the experimental group was significantly higher than that in the control group (73.33% vs. 53.57%, p < 0.05) and no significant differences were observed in the safety indices between the two groups (all p > 0.05). Our study shows that combining mild hypothermia and RIPC has a positive effect on brain protection and can significantly reduce the oxidative stress and associated outburst of inflammatory response. The Clinical Trial Registration number is ChiCTR2300073136.
RESUMO
Neurotoxicity was investigated in nano-SiO2-treated cultured PC12 cells, an in vitro neuronal cell model, in order to define a relatively safe dose range for its application. The following were observed in the present study: (1) A dose-dependent increase in the level of reactive oxygen species (ROS) with a corresponding decrease in the level of glutathione (R2=0.965) suggesting 20- and 50-nm SiO2-induced free radical generation and glutathione depletion. (2) A dose- and time-dependent decrease in cell viability that was associated with elevation of ROS level, especially after 24-h nano-SiO2 exposure (R2=0.965), suggesting the role of oxidative stress on nano-SiO2 induced cell death. (3) An increase in the level of thiobarbituric-acid reactive species that correlated reversely with cell viability of the PC12 cells treated with nano-SiO2 (R2=0.945) suggesting nano-SiO2-induced membrane damage caused by lipid peroxidation. (4) A dose-dependent increase in sub-G1 population in SiO2-exposed cells along with cell shrinkage and nuclear condensation from morphological examination suggesting nano-SiO2-induced cell apoptosis. Furthermore, nano-SiO2 exposure diminished the ability of neurite extension in response to nerve growth factor in treated PC12 cells. In summary, SiO2 nanoparticle exposure resulted in dose-dependent neurotoxicity in cultured PC12 cells that was probably associated with oxidative stress and induced apoptosis.