Attenuation of neuroinflammation by dexmedetomidine is associated with activation of a cholinergic anti-inflammatory pathway in a rat tibial fracture model

Zhu, Yajuan; Peng, Ke; Meng, Xiaowen; Ji, Fuhai

doi:10.1016/j.brainres.2016.04.074

Cited by 65 publications

(48 citation statements)

References 38 publications

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“…These data, however, do not preclude the possibility that other mechanisms may also contribute to activating hippocampal microglia during peripheral inflammation. The surgically-induced hippocampal production of MCP-1 we observed, however, does not preclude the possibility that mechanisms other than HMGB1 may also contribute to vagal afferents that can regulate microglia (32), cytokines crossing the BBB by diffusion or active transport and regulating microglia under feedback control (33), and receptors present on endothelial cells lining the BBB or CNS-penetrating blood vessels that may control microglial polarization (34). Future work should attempt to dissect the relative contribution of these putative mechanisms in the context of surgically induced trauma.…”

Section: Discussioncontrasting

confidence: 57%

Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice

Feng¹,

Valdearcos²,

Uchida³

et al. 2017

JCI Insight

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236

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Section: Discussioncontrasting

confidence: 57%

Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice

Feng¹,

Valdearcos²,

Uchida³

et al. 2017

JCI Insight

260

236

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“…Cytokines cause glial cell hypertrophy and prolif- eration, and release related proinflammatory cytokines, e.g., IL-1β, TNF-α, and IL-6, forming a network of autonomous activation [De Oliviera et al, 2011]. Recently, Zhu et al [2016] observed increased levels of cytokines and GFAP in the hippocampus of rats showing tibial fractures; this inflammatory cascade leads to postoperative neuroinflammation. Many other studies showed that experimental models of orthopedic surgery induced neuroinflammation via activation of the peripheral innate immune system.…”

Section: Discussionmentioning

confidence: 99%

“…In our previous study, dexmedetomidine reduced mechanical allodynia and hyperalgesia in a chronic constriction injury model of neuropathic pain [Farghaly et al, 2014]. Another study revealed that dexmedetomidine reduced hippocampal levels of cytokines in various pain conditions [Tanabe et al, 2014;Xie et al, 2015;Farghaly et al, 2016;Zhu et al, 2016]. They suggested that stimulation of α 2 -receptors during stress causes modulation of cytokine production by monocytes and macrophages, independently of adenylyl cyclase cAMP.…”

Section: Discussionmentioning

confidence: 99%

Reactive Astrogliosis in an Experimental Model of Fibromyalgia: Effect of Dexmedetomidine

Abd-ellatief

Mohamed

Kotb

2018

Cells Tissues Organs

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To our knowledge, this is the first study which investigates the induction of neuroinflammation in rats using an acidic-saline model of fibromyalgia. It is well known that the hippocampus has a fundamental role in pain perception, and astrocytes play a crucial role in pain signaling. Our aim is to evaluate the ability of dexmedetomidine to attenuate the inflammatory responses induced in astrocytes. In a group of healthy rats, induction of chronic muscle pain by intramuscular injection of 100 µL of acidic saline on days 0 and 5 resulted in peripheral sensitization (measured using the von Frey test) and significant (p < 0.05) increases in IL-1β (160.2 ± 1.1 to 335.2 ± 1.8), IL-6 (100.1 ± 1.4 to 202.4 ± 1.1), and TNF-α (60.0 ± 0.7 to 115.5 ± 1). Light and electron microscopy revealed degenerative changes in the hippocampus and reactive astrogliosis. Immunohistochemistry showed increased expression of glial fibrillary acid protein and inducible nitric oxide synthase. Surprisingly, treatment with a single dose of an α₂-adrenergic agonist, dexmedetomidine (5 µg/kg i.p.), attenuated these changes. This trial suggests that dexmedetomidine possibly directly acts on astrocytes, and a peripheral action is also suggested.

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“…For patients that are accompanied by a local infection and abnormal coagulation function during the cesarean section under general anesthesia, using dexmedetomidine for during delivery can reduce the dosage of propofol and remifentanil, and obtain favorable anesthesia (6). According to previous studies, it can be seen that different loading doses of dexmedetomidine have good sedative effects in TURP (7) and lower limb fracture surgery (8). In the present study, we will further explore the sedative effects of different loading doses of dexmedetomidine in cesarean section under combined spinal-epidural anesthesia.…”

Section: Introductionmentioning

confidence: 96%

Assessment of different loading doses of dexmedetomidine hydrochloride in preventing adverse reaction after combined spinal-epidural anesthesia

Jiang

Wang

et al. 2017

Experimental and Therapeutic Medicine

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We conducted the present study to investigate the effects of the different loading doses of dexmedetomidine hydrochloride in the prevention of adverse reactions after combined spinal-epidural anesthesia. A total of 200 patients that were admitted to the Department of Obstetrics at the Second Affiliated Hospital of Xi'an Jiaotong University hospital and treated with cesarean section through the use of combined spinal-epidural anesthesia from December, 2014 to June, 2016, were randomly divided into 4 groups. The therapeutic regimens of patients were shown as follows: group A was administered an intravenous pump of 10 ml/l physiological saline in surgery until the end of the delivery. group B was administered 0.2 µg/kg dexmedetomidine. group C was administered 0.4 µg/kg dexmedetomidine. group D was administered 0.6 µg/kg dexmedetomidine. The anesthesia plane was adjusted to the level below the T10 plane. After the onset of anesthesia, participants of each group were treated with an intravenous pump of dexmedetomidine at loading dose. After intravenous pumping for 10 min in each group during the surgery, patients were administered with an intraoperative maintenance dose of 0.2 µg/kg/h until the end of the delivery. The heart rate (HR), mean arterial pressure (MAP), Narcotrend index (NI), Ramsay sedation score and the incidence of adverse reactions at each time-point of the start of drug administration (T0), 10 min (T2), 30 min (T3), 60 min (T4), 90 min (T5) and the end of surgery (T6) were recorded. Within 24 h post-delivery, the degree of amnesia from using dexmedetomidine until the end of the delivery were followed up. Compared to group A and T0, the HRs of participants at T3-6 in groups B and C were decreased. The MAP at T1 in group D was increased. In groups B and C, the NIs were significantly decreased at T2-6, the Ramsay scores were increased at T3-6, and the differences were statistically significant (P<0.05). The follow-up within 24 h after delivery showed that the degree of anterograde amnesia from groups B to D was significantly higher than group A, with statistically significant difference (P<0.05). A combined spinal-epidural anesthesia with 0.6 µg/kg loading dose of dexmedetomidine, by intravenous pumping within 10 min before cesarean section, can achieve a satisfied sedative effect at 30 min after administration. It maintains the characteristics of intraoperative hemodynamic stability and less adverse reactions. Therefore, it is of great significance to improve the quality of cesarean section delivery.

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Attenuation of neuroinflammation by dexmedetomidine is associated with activation of a cholinergic anti-inflammatory pathway in a rat tibial fracture model

Cited by 65 publications

References 38 publications

Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice

Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice

Reactive Astrogliosis in an Experimental Model of Fibromyalgia: Effect of Dexmedetomidine

Assessment of different loading doses of dexmedetomidine hydrochloride in preventing adverse reaction after combined spinal-epidural anesthesia

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