Dexmedetomidine (DEX) is known to provide neuroprotective effect in the central nervous system. However, the detailed mechanism remains far more elusive. This study was designed to investigate the relevant mechanisms of DEX's neuroprotective effect. Sprague–Dawley (SD) rats were injected with dexmedetomidine and/or Lipopolysaccharide (LPS) intraperitoneally, and inflammatory cytokines in serum and in the hippocampus were measured by enzyme linked immunosorbent assay (ELISA). NF-κB in the brain tissue extracts was analyzed with western-blot. Then, we investigated whether NF-κB inhibitor prevents the elevation of inflammatory cytokines in rats injected with LPS. Our results indicated that compared with the control group, the rats exposed to LPS showed significant cognitive dysfunction. When compared to controls, the levels of TNF-α and IL-6 in the serum and hippocampus homogenate were increased in rats treated with LPS. DEX pretreatment inhibited the rats' TNF-α, IL-6 and NF-κB levels induced by LPS. In response to LPS, PDTC pretreatment restrains the production of proinflammatory cytokines (TNF-α and IL-6). Rats treated with PDTC and DEX alongside LPS exhibited less TNF-α and IL-6 than the LPS treated group. In combination, PDTC and DEX showed addictive effects. Our data suggest that DEX exerts a neuroprotective effect through NF-κB in part after LPS-induced cognitive dysfunction.
Background: Hypoxic-ischemic brain damage (HIBD) is the main cause of neurological dysfunction in neonates. Olfactory cognitive function is important for feeding, the ability to detect hazardous situations and social relationships. However, only a few studies have investigated olfactory cognitive dysfunction in neonates with HIBD; furthermore, the specific mechanisms involved are yet to be elucidated. It has been reported that neurogenesis in the subventricular zone (SVZ) is linked to olfactory cognitive function. Recently, dexmedetomidine (DEX) has been shown to provide neuroprotection in neonates following HIBD. In the present study, we investigated whether DEX could improve olfactory cognitive dysfunction in neonatal rats following HIBD and attempted to determine the underlying mechanisms.Methods: We induced HIBD in rats using the Rice–Vannucci model, and DEX (25 μg/kg, i.p.) was administered immediately after the induction of HIBD. Next, we used triphenyl tetrazolium chloride (TTC) staining and the Zea-longa score to assess the success of modelling. The levels of BDNF, TNF-α, IL-1β and IL-6 were determined by western blotting. Immunofluorescence staining was used to detect microglial activation and microglial M1/M2 polarization as well as to evaluate the extent of neurogenesis in the SVZ. To evaluate the olfactory cognitive function, the rats in each group were raised until post-natal days 28–35; then, we performed the buried food test and the olfactory memory test.Results: Analysis showed that HIBD induced significant brain infarction, neurological deficits, and olfactory cognitive dysfunction. Furthermore, we found that DEX treatment significantly improved olfactory cognitive dysfunction in rat pups with HIBD. DEX treatment also increased the number of newly formed neuroblasts (BrdU/DCX) and neurons (BrdU/NeuN) in the SVZ by increasing the expression of BDNF in rat pups with HIBD. Furthermore, analysis showed that the neurogenic effects of DEX were possibly related to the inhibition of inflammation and the promotion of M1 to M2 conversion in the microglia.Conclusion: Based on the present findings, DEX treatment could improve olfactory cognitive dysfunction in neonatal rats with HIBD by promoting neurogenesis in the SVZ and enhancing the expression of BDNF in the microglia. It was possible associated that DEX inhibited neuroinflammation and promoted M1 to M2 conversion in the microglia.
Dexmedetomidine, which is a highly selective α2 adrenoreceptor agonist, enhances the analgesic efficacy and prolongs the analgesic duration when administered in combination with local anesthetics. The current study aimed to evaluate the effects of dexmedetomidine combined with ropivacaine in ultrasound-guided transversus abdominis plane (TAP) block on post-operative analgesia following cesarean section (CS). A total of 70 patients scheduled for CS were divided randomly into 2 groups: The ropivacaine (R) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml 0.9% normal saline, and the dexmedetomidine (RD) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml dexmedetomidine (0.5 µg/kg). The primary outcome was pain-free duration, and secondary outcomes included heart rate (HR) and mean blood pressure (MBP) measurements, visual analogue scale (VAS) pain scores, number of patients who required rescue analgesic, time to first request for analgesia and patient satisfaction. There was no significant difference in HR and MBP between the two groups at 1 h post-surgery (P>0.05). However, VAS pain scores decreased at 6 and 8 h post-surgery [2 (1-2) vs. 0 (0-0.25) and 2 (2-3) vs. 0 (0-1), respectively; P<0.05], pain-free duration was prolonged (5.91±1.08 vs. 9.62±1.46 h; P<0.05), the number of patients who required rescue analgesic was reduced (19 vs. 9; P<0.05), the time to first request for analgesia was prolonged (7.10±1.21 vs. 11.60±2.11 h; P<0.05) and patient satisfaction was improved [3.5 (3-4) vs. 4 (4-5); P<0.05] in the RD group compared with the R group. Furthermore, no bradycardia or hypotension was observed. In conclusion, the results of the present study demonstrated that adding 0.5 µg/kg dexmedetomidine to 0.3% ropivacaine used in TAP block in patients undergoing CS prolonged pain-free duration, decreased VAS pain scores, reduced the number of patients who required rescue analgesic, prolonged the time to first request for analgesia and improved the patient satisfaction without serious side effects.
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