Although diverse effects of volatile anesthetics have been investigated in various studies, the mechanisms of action of such anesthetics, especially sevoflurane, remain elusive. In contrast to their potent modulation of inhibitory synaptic transmission there is little information about their effects on excitatory transmission in the brain. In this study, we examined the effect of sevoflurane on the excitatory synaptic transmission at CA1 synapses in hippocampal slices of mice. Sevoflurane at 5% was mixed with 95% O2 and 5% CO2 and bubbled in artificial cerebral spinal fluid (0.69 mM). Extracellular recordings of the field excitatory postsynaptic potential (fEPSP) and presynaptic fiber volley (FV) were made at physiological temperature. In addition, fluorescent measurements of presynaptic Ca2+ transients were performed while simultaneously recording fEPSP. Application of sevoflurane reduced the amplitude of fEPSP (45 ± 8%, n = 5). This effect was accompanied by concurrent enhancement of the paired-pulse facilitation of fEPSP (127 ± 5%, n = 12), suggesting a possible presynaptic site of action of sevoflurane. The amplitude of FV was not significantly affected (102 ± 5%, n = 5). In contrast, fluorescent measurements revealed that presynaptic Ca2+ influx was suppressed by sevoflurane (69 ± 5%, n = 7), as was simultaneously recorded fEPSP (44 ± 5%, n = 7). Our results suggest that sevoflurane potently suppresses excitatory synaptic transmission via inhibition of presynaptic Ca2+ influx without affecting presynaptic action potentials.
The innate immune system is a prerequisite for biophylactic ability, but its dysregulation can cause inflammatory and autoimmune diseases. To determine a safe method of controlling inflammatory reactions in the brain, we examined the effects of gnetin C, a natural resveratrol dimer, on C-C motif chemokine ligand 2 (CCL2) and CCL5 (pro-inflammatory chemokines) production observed after treatment with polyinosinic–polycytidylic acid [poly IC; a synthetic analog of dsRNA as a Toll-like receptor 3 (TRL3) ligand, 30 μg/mL] in cultured human astrocytoma U373MG and neuroblastoma SH-SY5Y cells. The addition of gnetin C (10 μM) to the media moderately reduced the CCL2 production and markedly suppressed CCL5 production in both cells. In the TLR3–interferon (IFN)-β–phosphorylated-STAT1 (signal transducer and activator of transcription protein 1)RIG-I (retinoic acid-inducible gene-I) pathway that mediates CCL2 and CCL5 production, gnetin C first inhibits IFN-β expression in SH-SY5Y cells and primarily inhibits STAT1 phosphorylation in U373MG cells. In any case, gnetin C attenuated the dsRNA-activated TLR3 signaling resulting in CCL2 and CCL5 production, thus, may be useful for controlling TLR3-mediated inflammation in the brain.
Essential oils have potential to mitigate stress symptoms and treat symptoms related to mental health. Few studies have investigated the effects of wood-derived aromatics on endocrinological and psychological responses in an actual space. In this study, we evaluated the effects of essential oil derived from Japanese cedar (Cryptomeria japonica) wood on the recovery state of female participants after they performed monotonous work. We determined the levels of salivary stress markers to describe the endocrinological responses. And we also used questionnaires to assess the perception of the odor of experimental rooms and psychological states. We found that olfactory stimulation with the volatile compounds of essential oil derived from Japanese cedar wood modulates mood states, and may transiently decrease sympathetic nervous activity. We suggest that olfactory stimulation with the volatile compounds of essential oil derived from Japanese cedar wood could be useful for maintaining mental health among women.
The present study aimed to investigate the protective effects of kamebakaurin (KA) and 1O, 20O-diacetyl kamebakaurin (Ac2KA) on acetaminophen (APAP)-induced hepatotoxicity and compare the hepatoprotective mechanisms of the two chemicals. Seven-week-old male C57BL/6J mice were orally administered KA, Ac2KA, or an ethanol/olive oil emulsion once per day for 7-days. Twenty-four hours after the final administration, the mice were fasted and then intraperitoneally injected with 450 mg/kg APAP or saline. At 16 h after injection, the mice were euthanized and blood samples were collected for plasma analysis. Pretreatment with KA and Ac2KA significantly attenuated APAP-induced hepatic injury. The protective effect of Ac2KA was stronger than that of KA. These two chemicals attenuated oxidative stress, inflammatory cytokine production, c-jun N-terminal kinase activation, and receptor-interacting protein (RIP)-3 activation. Ac2KA also decreased APAP-induced RIP-1 activation and nuclear factor kappa B (NF-κB) p65 translocation. Moreover, Ac2KA repressed mRNA expression of Cyp1a2/2e1 in the liver. Our results showed that KA and Ac2KA exerted protective effects against APAP-induced hepatotoxicity. The responsible mechanisms may be related to the chemicals’ antioxidant activity and the inhibition of c-jun N-terminal kinase activation and RIP-3 activation. The effects of Ac2KA included those of KA, as well as RIP-1 inactivation, NF-κB inhibition, and Cyp inhibition.
We evaluated the analgesic effects of minodronate, alendronate and pregabalin on mechanical and thermal allodynia, as well as changes in bone mineral density and skeletal muscle volume caused by chronic constriction injury (CCI) in an ovariectomized rat. Ovariectomy was performed on four-week-old female Wistar rats. Thereafter, at 8-weeks of age, the left sciatic nerve was ligated to create the chronic pain model (CCI limb), and sham surgery was performed on the right hindlimb. In all rats, either minodronate (0.15 mg/kg/week), alendronate (0.15 mg/kg/week), pregabalin (10 mg/kg/week), or their vehicle was administered for 2 weeks starting on the 0th day of CCI. Behavioral evaluations, with von Frey testing and the hot plate test, were performed on days 0, 7 and 14. After 2 weeks, bilateral femurs and tibialis anterior muscles were harvested for bone mineral density and cross sectional area measurements, respectively. Two weeks treatment with minodronate significantly improved mechanical and thermal allodynia evaluated by the von Frey and hot plate tests in the CCI limb (P < 0.05). Minodronate and alendronate treatment for 2 weeks significantly increased total femoral bone mineral density in the CCI limb compared with pregabalin or vehicle treatment (P < 0.01). Cross sectional area of the CCI limb in the minodronate group was significantly larger than that of the alendronate group (P < 0.05) and pregabalin group (P < 0.05). Two-week treatment with minodronate, but not alendronate or pregabalin, improved mechanical and thermal allodynia caused by CCI in ovariectomized rats.