Neuronal effects of SP600125 pretreatment in a rat model of cerebral ischemia/reperfusion injury Inhibited down-regulation of DNA repair protein

BACKGROUND： Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases （JNKs） signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE： To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi＇an Jiaotong University from June 2007 to September 2008. MATERIALS： SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK （Thr183/Tyr185） polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 （XRCC1） and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS： A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group （I/R group） were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group （pre-SP group） was given 10 μL SP600125 （3 μg/μL）. Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES： Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS： Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased （P 〈 0.01）. Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased （P 〈 0.01）. Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased （P 〈 0.05） following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group （P 〈 0.05）. Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region （r = -0.983, -0.953, P 〈 0.01）. CONCLUSION： SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.

Reducing surficial and interfacial defects by thiocyanate ionic liquid additive and ammonium formate passivator for efficient and stable perovskite solar cells

Organic–inorganic metal halide perovskites have attained extensive attention owing to their outstanding photovoltaic performances,but the existence of numerous defects in crystalline perovskites is still a serious constraint for the further development of perovskite solar cells(PSCs).In particular,the rapid crystallization guided by anti-solvents leads to plenty of surficial and interfacial defects in perovskite films.Herein,we report the adoption of a pseudo-halide anion based ionic liquid additive,1-butyl-3-methylimidazolium thiocyanate(BMIMSCN)for growing ternary cation(CsFAMA,where FA=formamidinium and MA=methylammonium)perovskites with large-scale crystal grains and strong preferential orientation via the enhanced Ostwald ripening.Meanwhile,a novel halide-free passivator,benzylammonium formate(BAFa),was employed as a buffering layer on the perovskite films to suppress surface-dominated charge recombination.As a result,the cooperative effects of BMIMSCN additive and BAFa passivator lead to significant enhancements on fluorescence lifetime(from 79.41 to 201.01 ns),open-circuit voltage(from 1.13 to 1.19 V),photoelectric conversion efficiency(from 18.90%to 22.33%).Moreover,the BMIMSCN/BAFa-CsFAMA PSCs demonstrated greatly improved stability against moisture and heat.This work suggests a promising strategy to improve the quality of perovskite materials via reducing the surficial and interfacial defects by the synergistic effects of lattice doping and interface engineering.