Abstract
BackgroundIschemic insults during operation can cause ischemic-reperfusion injuries in brain as well as memory impairments. Total intravenous anesthesia (TIVA) is the preferred anesthetic method in brain surgery, as it utilizes motor evoked potential monitoring. And the use of opioids is common in TIVA. However there are few studies about ischemic protective effect of opioids to glial cells.MethodsWe used mixed cultures of rat glial cells, which were harvested from the brain of 1-day old rat. We divided the experimental groups according to their hydromorphone conditioning period: (a) pre-culture, (b) per-culture, or (c) pre- and per-culture. We measured the levels of the reactive oxygen species (ROS) induced by tert-butyl hydroperoxide (TBH) using flow cytometry. The ROS levels in the glial cells were also measured after the administration of 100 nM hydromorphone and selective opioid receptor antagonists.ResultsThe ROS levels were reduced in the hydromorphone-treated group, as compared to the control group (only TBH treated). There were no differences between pre-conditioned and per-conditioned groups. However, the ROS levels were more reduced in pre- and per-conditioned group compared to pre-conditioned or per-conditioned only groups. Furthermore, selective antagonists for the delta, kappa, or mu opioid receptor partially negated the hydromorphone effect.ConclusionThis study demonstrated that hydromorphone can have additional protective effects on oxidative stress when pre- and per-conditioning is combined. Furthermore we proved that μ, δ, κ opioid receptors participate in protective mechanism of hydromorphone to glial cells.
Highlights
Ischemic insults during operation can cause ischemic-reperfusion injuries in brain as well as memory impairments
We evaluated whether hydromorphone had pre- and perconditioning effect on glial cells
The rat cerebral cortices were purified from the brains of 1-day old rat pups, and cultured in Dulbecco’s modified Eagle’s medium (DMEM) media supplemented with 10 % fetal bovine serum, 1 % antibiotics at 37 °C, and 5 % CO2 for 2 weeks
Summary
Ischemic insults during operation can cause ischemic-reperfusion injuries in brain as well as memory impairments. Total intravenous anesthesia (TIVA) is the preferred anesthetic method in brain surgery, as it utilizes motor evoked potential monitoring. There are few studies about ischemic protective effect of opioids to glial cells. Glial dysfunction can cause cognitive disorders as well as short-term memory loss (Vicente et al 2009; Maragakis and Rothstein 2006). Ischemic shock during surgery can induce ischemic-reperfusion injuries in the brain and memory impairments (Bilotta et al 2013). Many studies have established that opioids are protective against ischemia and reperfusion in different cell types (Gross et al 2010; Goldsmith et al.2013). There are few studies that evaluate the protective effects of opioids in glial cells under ischemic conditions. Opioids induce preconditioning effects in glial cells in the brain (Gwak et al 2010), it is unknown whether opioids have perconditioning effects
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