Dexmedetomidine Alleviates CCI-Induced Neuropathic Pain via Inhibiting HMGB1-Mediated Astrocyte Activation and the TLR4/NF-κB Signaling Pathway in Rats.

To investigate the effects of dexmedetomidine on chronic constriction injury (CCI)-induced neuropathic pain and to further explore its mechanism. A CCI rat model was established and treatment with dexmedetomidine. The paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were monitored at different time points, and the effects of hematoxylin-eosin staining on the sciatic nerve morphology of rats were observed. Immunohistochemical and immunofluorescence analyses were used to detect the expression of high mobility group box-1 (HMGB1) protein and glial fibrillary acidic protein (GFAP), and protein fluorescence intensity of GFAP in spinal cord tissue, respectively. Moreover, the expression of HMGB1 and Toll-like receptor-4/nuclear factor kappa-B (TLR4/NF-κB) pathway-related proteins were detected by western blot assay. To verify whether dexmedetomidine alleviates CCI-induced neuropathic pain by inhibiting HMGB1-mediated astrocyte activation and the TLR4/NF-κB signaling pathway, the rats were further treated with an HMGB1 activator or antagonist. Dexmedetomidine was found to improve the pathological changes of the sciatic nerve and alleviate pain in the CCI rats. The expression of HMGB1, GFAP, TLR4, TRAF6, MyD88, and p-P65 were greatly downregulated in the spinal cord tissues of the CCI rats. In addition, a further study showed that an HMGB1 activator can reverse the inhibition of neuropathic pain behaviors of dexmedetomidine. Overexpression of HMGB1 downregulated the PWMT and PWTL and enhanced the astrocyte activity and the TLR4/NF-κB signaling pathway in CCI rats. These results indicated that dexmedetomidine can alleviate neuropathic pain in CCI rats by inhibiting HMGB1-mediated astrocyte activation and the TLR4/NF-κB signaling pathway.

Neuroprotection of Resveratrol Against Focal Cerebral Ischemia/Reperfusion Injury in Mice Through a Mechanism Targeting Gut-Brain Axis.

Increasing evidences have shown that resveratrol could protect the brain from ischemic injury; the mechanisms underlying its neuroprotective effects are multifactorial and not fully understood. It remains unclear whether resveratrol could exert neuroprotection through modulating gut-brain axis, which plays important roles in stroke pathology. In this study, C57BL/6 mice underwent middle cerebral artery occlusion (60 min) followed by reperfusion for 3 days. Resveratrol, when applied immediately after MCAO onset for 3 days, promoted Th1/Th2 balance towards Th2 polarization and skewed Treg/Th17 balance towards Treg in the small intestinal lamina propria (SI-LP), and decreased small intestinal pro-inflammatory cytokines expression through modulating intestinal flora at 3 days post-ischemia (dpi). Resveratrol attenuated cerebral ischemia-induced increase in the epithelial and vascular permeability of small intestine as evidenced by reduced evans blue extravasasion and decreased protein leakage by feces/plasma albumin ratio at 3 dpi. The blood levels of pro-inflammatory cytokines at 3 dpi were also attenuated by resveratrol due to inhibiting intestinal pro-inflammatory immunity and decreasing epithelial and vascular permeability. Resveratrol robustly protected against post-stroke inflammation-induced blood-brain barrier disruption not only in the cortex but also in the striatum at 3 dpi. Furthermore, resveratrol mediated smaller cerebral infarcts and less neurological deficits via decreasing the levels of pro-inflammatory cytokines in the peri-infarct area at 3 dpi. Our results for the first time demonstrated that resveratrol may inhibit systemic post-stroke inflammation and neuroinflammation via modulating intestinal flora-mediated Th17/Tregs and Th1/Th2 polarity shift in SI-LP, which may be one of the mechanisms underlying the neuroprotective effects of resveratrol.

Analgesic effect of the midazolam-induced anesthesia in different doses on the patients after the thoracoscopic resection of lung cancer.

OBJECTIVE: To elaborate the analgesic efficiency of midazolam-induced anesthesia in different doses on the patients following the thoracoscopic resection of lung cancer. METHODS: Ninety patients undergoing thoracoscopic resection of lung cancer between August 2017 and July 2018 were randomized in the observation group (n = 45) and the control group (n = 45). Patients in observation group underwent the anesthesia induced by 0.1 mg/kg midazolam, while for the control group, the dose was adjusted to 0.05 mg/kg. Then, we compared the levels of inflammatory factors, SaO2, average of arterial pressure and changes in heart rate before and after surgery (48 h) to analyze the efficacy. RESULTS: At the postoperative 48 h, patients in the observation group had lower levels of inflammatory factors when comparing with their counterparts in the control group [IL-6, IL-8, IL-1ß and TNF-α: (58.44 ±â€¯3.22) µg/L, (2.04 ±â€¯0.26) µg/L, (2.98 ±â€¯0.44) µg/L, (5.33 ±â€¯0.77) µg/L v.s. (96.44 ±â€¯4.54) µg/L, (3.23 ±â€¯0.33) µg/L, (3.77 ±â€¯0.44) µg/L, (7.64 ±â€¯0.99) µg/L] (P < 0.05). Meanwhile, those in the observation group had a lower SaO2, average arterial pressure and heart rate [(93.79 ±â€¯1.08)%, (93.22 ±â€¯3.46) mmHg, (87.55 ±â€¯2.35) beat/min v.s. (97.13 ±â€¯1.03)%, (96.44 ±â€¯4.03) mmHg, (91.05 ±â€¯2.89) beat/min] (P < 0.05). However, no statistical significance was identified in the differences of the bleeding amount, surgical time and anesthesia time between two groups (P > 0.05), while the eye-opening time and the extubation time in the observation group were all shorter than those in the control group (P < 0.05). Similarly, the postoperative pain scores, total doses of propofol and remifentanil were also lowered (P < 0.05). CONCLUSION: For patients of thoracoscopic resection of lung cancer, midazolam-induced anesthesia (0.1 mg/kg) performs better than 0.5 mg/kg in inhibiting the inflammatory responses, with significant reduction in the dose of anesthetics, thereby stabilizing the status of patients in perioperative period and mitigating the postoperative pains. Thus, it is potential candidate.

Combined use of adult fiberoptic bronchoscope and CARTO catheter for tracheal intubation in children with known difficult airway.

PURPOSE: To find an alternative device to solve the difficult airway in children. METHOD: Fifteen patients, all ASA I-II, aged from 1.5 to 9 years, who were undergoing elective surgeries were included. Difficult endotracheal intubation, but not difficult ventilation, was possible for all. The adult fiberoptic bronchoscope (FOB) was used to provide a vision of the glottis, and the CARTO catheter (a cardiac interventional catheter) with adjustable tip was used to induce the endotracheal tube. RESULTS: All patients were successfully intubated within 1-2 min at the first attempt. CONCLUSION: Combined use of adult FOB and CARTO catheter may be an alternative device for tracheal intubation in children with known difficult airway.