Dexmedetomidine attenuates cerebral ischemia-reperfusion injury in rats by inhibiting the JNK pathway

Zhao, Bingxiao; Li, Da; Zhang, Shuchi; He, Liangmei; Ai, Yanqiu

doi:10.21037/apm-21-1218

Cited by 12 publications

(9 citation statements)

References 21 publications

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“…After administering dexmedetomidine, the PSD95–NR2B–nNOS interaction was decreased efficiently, and they found dexmedetomidine could enhance cognitive and motor recovery following TBI [ 9 ]. Another study showed that dexmedetomidine can alleviate cerebral ischemic reperfusion injury in rats by increasing the α2-adrenergic receptor and blocking JNK phosphorylation and the activation of caspase-3 [ 10 ]. Feng’s study showed that dexmedetomidine improves neurological outcomes in mice and reduces neuronal death by protecting against neural autophagy and neuroinflammation.…”

Section: Resultsmentioning

confidence: 99%

“…As a highly selective central agonist of the α2 adrenergic receptor, dexmedetomidine has been administered in many therapeutic procedures safely and efficiently [ 6 , 7 , 8 ]. Animal studies showed that dexmedetomidine reduced neuronal death by protecting against neural autophagy and neuroinflammation, enhanced cognitive and motor recovery following traumatic brain injury, and alleviated cerebral ischemic reperfusion injury [ 9 , 10 , 11 ]. Hence, dexmedetomidine was recommended in patients after craniotomy in recent years [ 12 , 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Comparing the Effect of Dexmedetomidine and Midazolam in Patients with Brain Injury

et al. 2022

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Background: Studies have shown that dexmedetomidine improves neurological function. Whether dexmedetomidine reduces mortality or improves quantitative electroencephalography (qEEG) among patients post-craniotomy remains unclear. Methods: This single-center randomized study was conducted prospectively from 1 January 2019 to 31 December 2020. Patients who were transferred to the ICU after craniotomy within 24 h were included. The analgesic was titrated to a Critical care Pain Observation Tool (CPOT) score ≤2, and the sedative was titrated to a Richmond Agitation–Sedation Scale (RASS) score ≤−3 for at least 24 h. The qEEG signals were collected by four electrodes (F3, T3, F4, and T4 according to the international 10/20 EEG electrode practice). The primary outcome was 28-day mortality and qEEG results on day 1 and day 3 after sedation. Results: One hundred and fifty-one patients were enrolled in this study, of whom 77 were in the dexmedetomidine group and 74 in the midazolam group. No significant difference was found between the two groups in mortality at 28 days (14.3% vs. 24.3%; p = 0.117) as well as in the theta/beta ratio (TBR), the delta/alpha ratio (DAR), and the (delta + theta)/(alpha + beta) ratio (DTABR) between the two groups on day 1 or day 3. However, both the TBR and the DTABR were significantly increased in the dexmedetomidine group. The DTABR in the midazolam group was significantly increased. The DAR was significantly increased on the right side in the dexmedetomidine group (20.4 (11.6–43.3) vs. 35.1 (16.7–65.0), p = 0.006) as well as on both sides in the midazolam group (Left: 19.5 (10.1–35.8) vs. 37.3 (19.3–75.7), p = 0.006; Right: 18.9 (10.1–52.3) vs. 39.8 (17.5–99.9), p = 0.002). Conclusion: Compared with midazolam, dexmedetomidine did not lead to a lower 28-day mortality or better qEEG results in brain injury patients after a craniotomy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparing the Effect of Dexmedetomidine and Midazolam in Patients with Brain Injury

et al. 2022

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“…Meanwhile, Dex has been found to have myocardial protection against hypertensive hypertrophic myocardial IRI [ 34 ]. Zhao et al [ 35 ] found that Dex alleviated cerebral IRI in rats by inhibiting c-un N-terminal Kinase (JNK) pathway. Moreover, Dex reduces Nod-like receptor family pyrin domain containing 3 (NLRP3) through adenosine monophosphate-activated kinase (AMPK), thereby improving NLRP3 inflammasome activation in alveolar macrophages mediated by renal ischemia-reperfusion [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axis

Chen

et al. 2022

BMC Anesthesiol

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Background Reperfusion of ischemic tissue has adverse impact on the myocardium. Dexmedetomidine (Dex) is a α2-adrenergic receptor (α2-AR) agonist with sedative and analgesic effects. Macrophage migration inhibition factor (MIF) is a pressure-regulating cytokine and is responsible for inflammatory and immune diseases. This study aims to reveal the consequences of Dex on myocardial ischemia-reperfusion injury (IRI) in young mice. Methods Fifty mice were raised and examined. At the end of the experiment, all mice were euthanized. The anterior descending department of the left coronary artery in mice was under ischemia for 60 min, then the ligation line was released and reperfused for 120 min to establish the IRI model. Mice were randomly divided into Sham, control, treatment using 4,5-dihydro-3-(4-hydroxyphenyl)-5-isoxazoleacetic acid (ISO-1), Dex treatment, and Dex combined ISO-1 treatment groups. Interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) and ATP levels were recorded. The expressions of MIF, P-adenosine monophosphate-activated kinase α (AMPKα), glucose transporter (GLUT)4, Bax and Bcl-2 were detected by Western Blot (WB). Hematoxylin and Eosin (H&E) staining was used to study cell morphology. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Echocardiography was carried out at the end of reperfusion, and the infarct size was calculated by Electron microscopy. Results I/R + Dex group showed significantly increased IL-6 and TNF-α levels and reduced myocardial cell necrosis and apoptosis. H&E staining showed alleviated myocardial disorder, myocardial cell swelling, myocardial fiber fracture, and inflammatory cell infiltration in I/R + Dex group. Myocardial cell necrosis and apoptosis were significantly reduced in I/R + Dex group. ATP level in myocardial tissue of mice in I/R group was substantially decreased, while that in Dex group was increased. WB results showed that MIF, P-AMPK α, GLUT4 and Bcl-2 levels were increased and Bax levels were decreased in I/R + Dex group. Conclusion Dex may exert myocardial protection in young mice through MIF/AMPK/GLUT4 axis.

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“…Additionally, XST can reduce neurological dysfunction and pathological damage in CI/R rats [ 21 ]. In contrast, dexmedetomidine (Dex) is an anesthesia-assisted sedative and a potent and highly selective α 2 adrenoceptor agonist [ 22 ]. Some studies have reported the neuroprotective effects of Dex in animal models of brain injury.…”

Section: Introductionmentioning

confidence: 99%

“…Some studies have reported the neuroprotective effects of Dex in animal models of brain injury. For instance, Zhao et al reported that Dex could relieve CI/R injury in rats by activating α 2-adrenergic receptors and blocking JNK phosphorylation and caspase-3 activation [ 22 ]. Sun et al claimed that the neuroprotective effects of Dex were achieved by suppressing spinal cord inflammation and neuronal apoptosis and alleviating spinal cord CI/R injury [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue

Han

Min

et al. 2022

Oxidative Medicine and Cellular Longevity

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Ischemic stroke is the most common type of cerebrovascular disease with high mortality and poor prognosis, and cerebral ischemia-reperfusion (CI/R) injury is the main murderer. Here, we attempted to explore the effects and mechanism of Xuesaitong (XST) combined with dexmedetomidine (Dex) on CI/R injury in rats. First, a rat model of CI/R injury was constructed via the middle cerebral artery occlusion (MCAO) method and treated with XST and Dex alone or in combination. Then, on the 5th and 10th days of treatment, the neurological impairment was assessed using the modified neurological severity scores (mNSS), the 8-arm radial maze test (8ARMT), novel object recognition test (NORT), and fear conditioning test (FCT). H&E staining was performed to observe the pathological changes of the hippocampus. ELISA and related kits were used to assess the monoamine neurotransmitters and antioxidant enzyme activities in the hippocampus. The ATP, mitochondrial membrane potential levels, and qRT-PCR of genes related to mitochondrial function were determined to assess mitochondrial functions in the hippocampus and western blot to determine Keap1/Nrf2 signaling pathway and mitophagy-related protein expression. The results showed that XST combined with Dex significantly reduced mNSS, improved spatial memory and learning deficits, and enhanced fear memory and cognitive memory ability in CI/R rats, which was superior to single-drug treatment. Moreover, XST combined with Dex treatment improved hippocampal histopathological damage; significantly increased the levels of monoamine neurotransmitters, neurotrophic factors, ATP, and mitochondrial membrane potential; and upregulated the activities of antioxidant enzymes and the expression of mitophagy-related proteins in the hippocampus of CI/R rats. XST combined with Dex treatment also activated the Keap1/Nrf2 signaling and upregulated the protein expression of downstream antioxidant enzymes HO-1 and NQ. Altogether, this study showed that a combination of XST and Dex could activate the Keap1/Nrf2 signaling and mitophagy to protect rats from CI/R-related neurological impairment.

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Dexmedetomidine attenuates cerebral ischemia-reperfusion injury in rats by inhibiting the JNK pathway

Cited by 12 publications

References 21 publications

Comparing the Effect of Dexmedetomidine and Midazolam in Patients with Brain Injury

Comparing the Effect of Dexmedetomidine and Midazolam in Patients with Brain Injury

Dexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axis

Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue

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