Nimodipine attenuates neuroinflammation and delayed apoptotic neuronal death induced by trimethyltin in the dentate gyrus of mice.

L-type voltage-gated calcium channels (L-VGCCs) are thought to be involved in epileptogenesis and acute excitotoxicity. However, little is known about the role of L-VGCCs in neuroinflammation or delayed neuronal death following excitotoxic insult. We examined the effects of repeated treatment with the L-VGCC blocker nimodipine on neuroinflammatory changes and delayed neuronal apoptosis in the dentate gyrus following trimethyltin (TMT)-induced convulsions. Male C57BL/6 N mice were administered TMT (2.6 mg/kg, i.p.), and the expression of the Cav1.2 and Cav1.3 subunits of L-VGCC were evaluated. The expression of both subunits was significantly decreased; however, the astroglial expression of Cav1.3 L-VGCC was significantly induced at 6 and 10 days after TMT treatment. Furthermore, astroglial Cav1.3 L-VGCCs colocalized with both the pro-inflammatory phenotype marker C3 and the anti-inflammatory phenotype marker S100A10 of astrocytes. Nimodipine (5 mg/kg, i.p. × 5 at 12-h intervals) did not significantly affect TMT-induced astroglial activation. However, nimodipine significantly attenuated the pro-inflammatory phenotype changes, while enhancing the anti-inflammatory phenotype changes in astrocytes after TMT treatment. Consistently, nimodipine reduced the levels of pro-inflammatory astrocytes-to-microglia mediators, while increasing the levels of anti-inflammatory astrocytes-to-microglia mediators. These effects were accompanied by an increase in the phosphorylation of extracellular signal-regulated kinase (ERK), supporting our previous finding that p-ERK is a signaling factor that regulates astroglial phenotype changes. In addition, nimodipine significantly attenuated TMT-induced microglial activation and delayed apoptosis of dentate granule neurons. Our results suggest that L-VGCC blockade attenuates neuroinflammation and delayed neurotoxicity following TMT-induced convulsions through the regulation of astroglial phenotypic changes by promoting ERK signaling.

Synergistic effects of cellulose nanocrystal on the mechanical and shape memory properties of TPU composites.

Cellulose nanocrystal is a nanomaterial that has a large specific surface area, high surface energy, and high strength. As well, it is biocompatible, environmentally friendly, nontoxic, and can be extracted from biomass resources. Because of these features, cellulose nanocrystals can be used to improve the mechanical properties of polymer matrices with a shape memory effect and as a shape memory switch. In this study, a polytrimethylene ether glycol-based thermoplastic polyurethane (TPU)/cellulose nanocrystal (CNC) composite was prepared via an in-situ polymerization process to create a self-healing polymer matrix. Also, the effect of CNC doses in low concentrations (≤2 wt%) on the different properties of the resulting bio-nanocomposite was investigated. The results showed that the introduction of CNCs affects the hydrogen bonding within the polymer matrix and provides better thermal stability in the high temperature range than pure TPU. Furthermore, the samples with 0 wt%, 0.75 wt%, 1 wt%, and 2 wt% of CNC exhibited an increasing trend in tensile strength with values of 11.71 MPa, 18.95 MPa, 17.88 MPa, and 26.18 MPa, respectively, which indicates a remarkable improvement in mechanical strength. The shape memory behavior was also notably prominent in this polymer composite, where the composite containing 2 wt% of CNC showed the fastest recovery time (240 s) at 75 °C with the highest shape retention. Moreover, their flow behavior and deformation capacity were examined through rheology tests. Besides, docking simulations were conducted in silico to assess the interaction of the TPU/CNC composite with the DNA gyrase enzyme. The interaction between CNC/TPU composite and DNA gyrase was meticulously analyzed across 10 distinct conformations, yielding docking scores ranging from -6.5 Kcal/mol to -5.3 Kcal/mol. Overall, the physico-mechanical properties of the TPU/CNC composites were substantially enhanced with the incorporation of nanofillers.

Ginsenoside Re protects against kainate-induced neurotoxicity in mice by attenuating mitochondrial dysfunction through activation of the signal transducers and activators of transcription 3 signaling.

It was demonstrated that ginsenosides exert anti-convulsive potentials and interleukin-6 (IL-6) is protective from excitotoxicity induced by kainate (KA), a model of temporal lobe epilepsy. Ginsenosides-mediated mitochondrial recovery is essential for attenuating KA-induced neurotoxicity, however, little is known about the effects of ginsenoside Re (GRe), one of the major ginsenosides. In this study, GRe significantly attenuated KA-induced seizures in mice. KA-induced redox changes were more evident in mitochondrial fraction than in cytosolic fraction in the hippocampus of mice. GRe significantly attenuated KA-induced mitochondrial oxidative stress (i.e. increases in reactive oxygen species, 4-hydroxynonenal, and protein carbonyl) and mitochondrial dysfunction (i.e. the increase in intra-mitochondrial Ca2+ and the decrease in mitochondrial membrane potential). GRe or mitochondrial protectant cyclosporin A restored phospho-signal transducers and activators of transcription 3 (STAT3) and IL-6 levels reduced by KA, and the effects of GRe were reversed by the JAK2 inhibitor AG490 and the mitochondrial toxin 3-nitropropionic acid (3-NP). Thus, we used IL-6 knockout (KO) mice to investigate whether the interaction between STAT3 and IL-6 is involved in the GRe effects. Importantly, KA-induced reduction of manganese superoxide dismutase (SOD-2) levels and neurodegeneration (i.e. astroglial inhibition, microglial activation, and neuronal loss) were more prominent in IL-6 KO than in wild-type (WT) mice. These KA-induced detrimental effects were attenuated by GRe in WT and, unexpectedly, IL-6 KO mice, which were counteracted by AG490 and 3-NP. Our results suggest that GRe attenuates KA-induced neurodegeneration via modulating mitochondrial oxidative burden, mitochondrial dysfunction, and STAT3 signaling in mice.