Stellate ganglion block ameliorated central post-stroke pain with comorbid anxiety and depression through inhibiting HIF-1α/NLRP3 signaling following thalamic hemorrhagic stroke.

BACKGROUND: Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients' lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. METHODS: Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. RESULTS: Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. CONCLUSION: This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.

Poly[bis-[µ2-4,4'-bis-(imidazol-1-ylmeth-yl)biphenyl-κ2 N:N']di-chlorido-nickel(II)].

In the title compound, [NiCl2(C20H18N4)2] n , the Ni2+ cation is situated on an inversion center and is coordinated by two chloride ions and four imidazole N atoms of four different 4,4'-bis-[(1H-imidazol-1-yl)meth-yl]-1,1'-biphenyl (BIMB), forming a slightly distorted octa-hedral geometry. Each BIMB ligand adopts a linear linker to connect Ni2+ ions, forming a two-dimensional layer with an sql network. In the crystal, neighboring layers repeat in an ABAB stacking mode, and weak inter-molecular C-H⋯Cl hydrogen bonds between alternate layers lead to a three-dimensional, twofold inter-penetrated, supra-molecular framework with a pcu topology net.

The Relationship of the Test for Respiratory and Asthma Control in Kids Initial Score on the Prognosis of Pre-school Children With Asthma: A Prospective Cohort Study.

Objective: The test for respiratory and asthma control in kids (TRACK) is currently the only standard follow-up tool for children under 5 years of age with asthma. The purpose of this study was to investigate the relationship between the TRACK initial score (Ti) and their prognosis after 6 months of follow-up in pre-schoolers with asthma. Design: A prospective cohort study. Methods: The study included pre-schoolers diagnosed with asthma at the Shanghai Children's Medical Center between January 2019 and June 2020, and follow-up for 6 months. TRACK scores, frequency of wheezing and respiratory infections, number of Emergency Department (ED) visits and treatment regimen were collected. According to the TRACK initial score, the children were divided into "Ti < 60 group" and "Ti ≥ 60 group," and the two groups were compared in terms of TRACK score related indicators, clinical manifestations and treatment. Results: There are 102 pre-schoolers included in the analysis [78 boys (76.5%) and 24 girls (23.5%); mean (SD) age, 28.05 (11.63) months]. After 6 months of follow-up, the TRACK score was improved in both groups, and the "Ti ≥ 60 group" had a higher score, lower rate of uncontrolled asthma and fewer reassessments were required. There was no difference in the number of wheezing attacks between the two groups in terms of clinical presentation, but the "Ti < 60 group" had more respiratory infections and ED visits. Regarding the use of ICSs, in the "Ti < 60 groups," the dose of ICSs was higher and reduced slowly, and the dose difference between the two groups began to appear after 5 months of follow-up. Conclusion: TRACK is essential for pre-schoolers with asthma at the time they are diagnosed. In addition, if the TRACK initial score is < 60, the probability of poor prognosis is higher.

Doping gadolinium versus lanthanum into hydroxyapatite particles for better biocompatibility in bone marrow stem cells.

Lanthanide ions (Ln3+) doped hydroxyapatite (HAP) particles are well established in biomedical areas. Although Ln elements are closely located in the periodic table and have plenty of similar characteristics, the minor differences in the effective ionic radii could cause alterations in the physicochemical and biological properties of HAP substitutes. The present study synthesized lanthanum-(La-) and gadolinium-(Gd-) doped HAP particles (La-HAP and Gd-HAP). And the effects of two types of particles on bone marrow stem cells (BMSCs) viability were also measured and compared in vitro. The results indicated that the Gd-HAP adsorbed more serum proteins from culture media and inhibited the new layer of apatite formation on its surface when comparing to La-HAP with a similar crystalline structure, particle size, and Zeta potential. These surface modifications can significantly reduce the cell adhesion of Gd-HAP, simultaneously decreasing the Gd-HAP particle uptake efficiency. Moreover, the cell viability of Gd-HAP remained higher than that of La-HAP in culture periods. We concluded that a slight variation in the effective ionic radii between Gd3+ and La3+ could alter the adsorption of serum proteins on the particles' surface, modulating subsequent cellular responses. The present work provides an interesting view that Gd-HAP is endowed with better cellular biocompatibility than La-HAP.