Effects of propofol-dexmedetomidine combination on ischemia reperfusion-induced cerebral injury

Wang, Zhun; Kou, Dang-pei; Li, Zhao-duan; He, Yan; Yu, Wenli; Du, Hongyin

doi:10.3233/nre-141177

Cited by 26 publications

(20 citation statements)

References 40 publications

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“…Isoflurane (Iso) exerted neuroprotection by reducing the expression of the TLR4-mediated NF-κB signalling pathway and alleviating microglial activation after cerebral I/R injury in vitro and in vivo [ 21 ]. In addition, perioperative treatment with propofol (Pro) and Dex significantly suppressed cerebral I/R injury and upregulation of TNF-α and IL-1β in rats [ 22 ]. Thus, we hypothesised that there might be a link between Dex-induced spinal cord neuroprotection and both TLR4 activity and microglial activation.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits

Sun

Zhao

et al. 2018

J Transl Med

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BackgroundDexmedetomidine (Dex) can improve neuronal viability and protect the spinal cord from ischemia–reperfusion (I/R) injury, but the underlying mechanisms are not fully understood. This study investigated the effects of dexmedetomidine on the toll-like receptor 4 (TLR4)-mediated nuclear factor κB (NF-κB) inflammatory system and caspase-3 dependent apoptosis induced by spinal cord ischemia–reperfusion injury.MethodsTwenty-four rabbits were divided into three groups: I/R, Dex (10 µg/kg/h prior to ischemia until reperfusion), and Sham. Abdominal aortic occlusion was carried out for 30 min in the I/R and Dex groups. Hindlimb motor function was assessed using the Tarlov scoring system for gait evaluation. Motor neuron survival and apoptosis in the ventral grey matter were assessed by haematoxylin–eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labelling staining. The expression and localisation of ionised calcium-binding adaptor molecule 1, TLR4, NF-κB and caspase-3 were assessed by immunoreactivity analysis. The levels of interleukin 1β and tumour necrosis factor α were assessed using enzyme-linked immunosorbent assays.ResultsPerioperative treatment with dexmedetomidine was associated with a significant preservation of locomotor function following spinal cord ischemia–reperfusion injury with increased neuronal survival in the spinal cord compared to control. In addition, dexmedetomidine suppressed microglial activation, inhibited the TLR4-mediated NF-κB signalling pathway, and inhibited the caspase-3 dependent apoptosis.ConclusionsDexmedetomidine confers neuroprotection against spinal cord ischemia–reperfusion injury through suppression of spinal cord inflammation and neuronal apoptosis. A reduction in microglial activation and inhibition of both the TLR4-mediated NF-κB signalling pathway and caspase-3 dependent apoptosis are implicated.

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Section: Introductionmentioning

confidence: 99%

Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits

Sun

Zhao

et al. 2018

J Transl Med

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“…Dexmedetomidine (Dex), a highly selective α 2 -adrenoceptor agonist, previously provided neuroprotection against ischemia reperfusion-induced cerebral injury ( 20 , 21 ), transient spinal ischemia ( 22 ) and isoflurane-induced neuroapoptosis ( 23 ). However, the underlying mechanisms of these processes have not been fully determined.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of dexmedetomidine on traumatic brain injury: Involvement of neuronal apoptosis and HSP70 expression

et al. 2018

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The aim of the present study was to investigate the protective effect of dexmedetomidine (Dex) on traumatic brain injury (TBI), and further evaluate whether the underlying neuroprotective mechanisms are associated with neurological apoptosis and the expression of 70 kDa heat shock protein (HSP70) in the hippocampus. A total of 90 adult male Sprague-Dawley rats were randomly assigned into 3 groups (n=30/group): Sham, TBI and Dex groups. The rat models of TBI were established using a modified weight-drop device and Dex (15 µg/kg) was intravenously administered immediately following TBI. The brain edema and neurological function outcomes of TBI were assessed using wet-dry weight analysis and the Neurological Severity Score method. The expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in the rat hippocampus were evaluated using immunohistochemical staining and western blot analysis. The protein levels of HSP70 in the hippocampal region were analyzed using western blot analysis. The results of the present study revealed that administration of Dex post-TBI improved brain edema and neurological outcomes, due to the attenuation of the TBI-induced reduction of Bax expression and increase of Bcl-2 and HSP70 expression. In conclusion, the results of the present study suggested that administration of Dex may serve as a neuroprotective agent against brain injury, at least partially via the inhibition of neuronal apoptosis and upregulation of HSP70 expression in the hippocampus.

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“…Among them, dexmedetomidine (Dex), a potent and highly selective α2-adrenoceptor agonist and a widely used auxiliary anesthetic, has previously been reported to reduce isoflurane- and ketamine-induced neuroapoptosis in vivo and in vitro ( 15 , 16 ). The neuroprotective effect of Dex may be associated with its anti-oxidant ( 17 ) and anti-apoptotic ( 15 ) activity, its positive impact on astrocyte brain-derived neurotrophic factor expression ( 18 ), or inhibition of the PI3K/Akt/GSK-3β pathway ( 19 ). However, the effect of Dex on propofol-induced neurotoxicity in the developing brain has not been determined.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine attenuates repeated propofol exposure-induced hippocampal apoptosis, PI3K/Akt/Gsk-3β signaling disruption, and juvenile cognitive deficits in neonatal rats

Wang

Han

et al. 2016

Molecular Medicine Reports

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Propofol is one of the most widely used intravenous anesthetics. However, repeated exposure to propofol may cause neurodegeneration in the developing brain. Dexmedetomidine (Dex), an α2 adrenoceptor agonist, has been previously demonstrated to provide neuroprotection against neuroapoptosis and neurocognitive impairments induced by several anesthetics. Thus, the current study aimed to investigate the effect of Dex on neonatal propofol-induced neuroapoptosis and juvenile spatial learning/memory deficits. Propofol (30 mg/kg) was intraperiotoneally administered to 7-day-old Sprague Dawley rats (n=75) three times each day at 90 min intervals for seven consecutive days with or without Dex (75 µg/kg) treatment 20 min prior to propofol injection. Following repeated propofol exposure, reduced Akt and GSK-3β phosphorylation, increased cleaved caspase-3 expression levels, an increased Bax/Bcl-2 ratio, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in the CA1 hippocampal subregion were observed. Morris Water Maze testing at postnatal day 29 also demonstrated spatial learning and memory deficits following propofol treatment compared with the control group. Notably, these changes were significantly attenuated by Dex pretreatment. The results of the current study demonstrated that Dex ameliorates the neurocognitive impairment induced by repeated neonatal propofol challenge in rats, partially via its anti-apoptotic action and normalization of the disruption to the PI3K/Akt/GSK-3β signaling pathway. The present study provides preliminary evidence demonstrating the safety of propofol on the neonatal brain and the potential use of dexmedetomidine pretreatment in pediatric patients.

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Effects of propofol-dexmedetomidine combination on ischemia reperfusion-induced cerebral injury

Cited by 26 publications

References 40 publications

Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits

Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits

Neuroprotective effects of dexmedetomidine on traumatic brain injury: Involvement of neuronal apoptosis and HSP70 expression

Dexmedetomidine attenuates repeated propofol exposure-induced hippocampal apoptosis, PI3K/Akt/Gsk-3β signaling disruption, and juvenile cognitive deficits in neonatal rats

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