Stroke results in inflammation, brain edema, and neuronal death. However, effective neuroprotectants are not available. Recent studies have shown that high mobility group box-1 (HMGB1), a proinflammatory cytokine, contributes to ischemic brain injury. Aquaporin 4 (AQP4), a water channel protein, is considered to play a pivotal role in ischemia-induced brain edema. More recently, studies have shown that pannexin 1 channels are involved in cerebral ischemic injury and the cellular inflammatory response. Here, we examined whether the pannexin 1 channel inhibitor probenecid could reduce focal ischemic brain injury by inhibiting cerebral inflammation and edema. Transient focal ischemia was induced in C57BL/6J mice by middle cerebral artery occlusion (MCAO) for 1 h. Infarct volume, neurological score and cerebral water content were evaluated 48 h after MCAO. Immunostaining, western blot analysis and ELISA were used to assess the effects of probenecid on the cellular inflammatory response, HMGB1 release and AQP4 expression. Administration of probenecid reduced infarct size, decreased cerebral water content, inhibited neuronal death, and reduced inflammation in the brain 48 h after stroke. In addition, HMGB1 release from neurons was significantly diminished and serum HMGB1 levels were substantially reduced following probenecid treatment. Moreover, AQP4 protein expression was downregulated in the cortical penumbra following post-stroke treatment with probenecid. These results suggest that probenecid, a powerful pannexin 1 channel inhibitor, protects against ischemic brain injury by inhibiting cerebral inflammation and edema.

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Serious complications were very rare; only one patient had permanent sequelae, and a single epidural hematoma was diagnosed. Post-operative neurologic deficits were more common, but most complications resolved spontaneously within 3 months and they rarely required intervention.

Background:Intravenous (IV) oxycodone has been used at induction to prevent an intubation reaction. The aims of the current study were to calculate the median effective dose (ED50) and the 95% effective dose (ED95) of an IV bolus of oxycodone that blunts the hemodynamic response to tracheal intubation with propofol according to gender and to observe the adverse events of induction-dose oxycodone.Methods:Adult patients who required general anesthesia and tracheal intubation were enrolled. Tracheal intubation was performed using unified TD-C-IV video laryngoscopy and an ordinary common endotracheal tube. Dixon's up-and-down method was used to obtain ED50 data for women and men separately. The initial dose of oxycodone was 0.2 mg/kg for women and 0.3 mg/kg for men (step size was 0.01 mg/kg). Next, a dose-response curve from the probit analysis was generated to determine the ED50 and ED95 to blunt the intubation reaction in female and male patients. Adverse events following oxycodone injection were observed for 5 min before propofol injection.Results:Sixty-three patients were analyzed, including 29 females and 34 males. According to the probit analysis, the ED50 and ED95 of oxycodone required to blunt the intubation reaction in women were 0.254 mg/kg (95% confidence interval [CI], 0.220–0.328 mg/kg) and 0.357 mg/kg (95% CI, 0.297–2.563 mg/kg), respectively. In men, the ED50 and ED95 were 0.324 mg/kg (95% CI, 0.274–0.381 mg/kg) and 0.454 mg/kg (95% CI, 0.384–2.862 mg/kg), respectively. Men required 28% more oxycodone than women for induction (P < 0.01). The most common adverse events were dizziness (87.3%), vertigo (66.7%), sedation (74.6%), and respiratory depression (66.7%).Conclusions:Oxycodone can be used for induction to prevent intubation reactions. Gender affected the ED50 and ED95 of oxycodone for blunting the tracheal intubation reaction.

Orexin is a neuropeptide that is primarily synthesized and secreted by the lateral hypothalamus (LH) and includes two substances derived from the same precursor (orexin A [OXA] and orexin B [OXB]). Studies have shown that orexin is not only involved in the regulation of eating, the sleep–wake cycle, and energy metabolism, but also closely associated with various physiological functions, such as cardiovascular control, reproduction, stress, reward, addiction, and the modulation of pain transmission. At present, studies that have been performed both domestically and abroad have confirmed that orexin and its receptors are closely associated with pain regulation. In this article, the research progress on acute pain regulation involving orexin is reviewed.