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

Zhang, Man‐He; Zhou, Xiumin; Wang, Kai‐Jie; Feng, Yan; Zhang, Hong‐Ao

doi:10.3892/mmr.2018.8898

Cited by 34 publications

(26 citation statements)

References 44 publications

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“…The Bcl‐2 family consists of antiapoptotic (Bcl‐2) and proapoptotic (Bax) factors. The pro‐apoptotic family members trigger cytokine release into the cytoplasm, leading to caspase activation . In present study, Bax and Bcl‐2 expression levels were detected using Western blotting.…”

Section: Discussionmentioning

confidence: 85%

“…Dexmedetomidine (DEX) is a central adrenoceptor α 2‐adrenergic receptor agonist with sedative, analgesic, and anti‐stress reaction effects . DEX affects neurons and exerts protective effects by decreasing catecholamine and glutamate levels and preventing neuronal apoptosis . Previous studies demonstrated that suppressing proinflammatory cytokine production in the brain played a crucial role in DEX–induced neuroprotection after cerebral ischemia/reperfusion injury .…”

Section: Introductionmentioning

confidence: 99%

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Dexmedetomidine Attenuates Neuroinflammatory–Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway

Xiao-dong

Zhang

et al. 2019

Ann Clin Transl Neurol

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Objective Dexmedetomidine (DEX) exhibits neuroprotective effects as a multifunctional neuroprotective agent in numerous neurological disorders. However, in traumatic brain injury (TBI), the molecular mechanisms of these neuroprotective effects remain unclear. The present study investigated whether DEX, which has been reported to exert protective effects against TBI, could attenuate neuroinflammatory‐induced apoptosis and clarified the underlying mechanisms. Methods A weight‐drop model was established, and DEX was intraperitoneally injected 30 min after inducing TBI in rats. The water content in the brain tissue was measured. Terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL) assays were performed on histopathological tissue sections to evaluate neuronal apoptosis. Enzyme‐linked immunosorbent assay and PCR were applied to detect the levels of the inflammatory factors, TNF‐α, IL‐1β, IL‐6, and NF‐κB. Results TBI–challenged rats exhibited significant neuronal apoptosis, which was characterized via the wet‐to‐dry weight ratio, neurobehavioral functions, TUNEL assay results and the levels of cleaved caspase‐3, Bax upregulation and Bcl‐2, which were attenuated by DEX. Western blot, immunohistochemistry, and PCR results revealed that DEX promoted Nrf2 expression and upregulated expression of the Nrf2 downstream factors, HO‐1 and NQO‐1. Furthermore, DEX treatment markedly prevented the downregulation of inflammatory response factors, TNF‐α, IL‐1β and NF‐κB, and IL‐6. Interpretation Administering DEX attenuated inflammation‐induced brain injury in a TBI model, potentially via the Nrf2 signaling pathway.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine Attenuates Neuroinflammatory–Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway

Xiao-dong

Zhang

et al. 2019

Ann Clin Transl Neurol

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“…Zhang et al (37) recently reported that HSP70 conferred cellular protection against ischemic insults and possessed potent anti-apoptotic properties in hippocampal neurons using a traumatic brain injury rat model. To further understand the role of apoptosis and autophagy in neurons after I/R, protein expression levels of Bax, Bcl-2, Caspase-3 and Beclin1 were analyzed in the present study.…”

Section: Discussionmentioning

confidence: 99%

Hypothermic properties of dexmedetomidine provide neuroprotection in rats following cerebral ischemia‑reperfusion injury

Liu

Zhu

et al. 2019

Exp Ther Med

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Dexmedetomidine (Dex) is a sedative and analgesic agent that is widely administered to patients admitted to the intensive care unit, and has been demonstrated to result in hypothermia. Many patients have been revealed to benefit from therapeutic hypothermia, which can mitigate cerebral ischemia/reperfusion (I/R) injury following successful cardiopulmonary resuscitation. However, studies investigating the efficacy of Dex in I/R treatment is lacking. The present study aimed to investigate the efficacy of Dex in mitigating neuronal damage, and to determine the possible mechanism of its effects in a rat model of cardiac arrest (CA). CA was induced in Sprague-Dawley rats by asphyxiation for 5 min. Following successful resuscitation, the surviving rats were randomly divided into two treatment groups; one group was intraperitoneally administered with Dex (D group), whereas the control group was treated with normal saline (N group). Critical parameters, including core temperature and blood pressure were monitored following return of spontaneous circulation (ROSC). Arterial blood samples were collected at 10 min after surgery (baseline) 30 and 120 min post-ROSC; and neurological deficit scores (NDS) of the rats were taken 12 or 24 h after ROSC prior to euthanasia. The hippocampal tissue was then removed for analysis by histology, electron microscopy and western blotting. Rats in the D group exhibited a lower core temperature and higher NDS scores compared with the N group (P<0.05). In addition, Dex injection resulted in reduced expression of apoptotic and autophagy-associated factors in the hippocampus (P<0.05). Dex treatment induced hypothermia and improved neurological function in rats after ROSC following resuscitation from CA by inhibiting neuronal apoptosis and reducing autophagy, which suggested that Dex may be a potential therapy option for patients with CA.

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“…A previous study has demonstrated that dexmedetomidine can serve as a neuroprotective agent against brain injury via the inhibition of neuronal apoptosis ( 34 ). Sun et al ( 35 ) identified that dexmedetomidine confers neuroprotection against spinal cord ischemia-reperfusion injury via the suppression of spinal cord inflammation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Effects of local dexmedetomidine administration on the neurotoxicity of ropivacaine for sciatic nerve block in rats

Xue

Fan

et al. 2020

Mol Med Rep

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dexmedetomidine, used as an adjuvant to local anesthetics (las), may prolong the duration of peripheral nerve block. However, the effect of dexmedetomidine on the neurotoxicity of las is not completely understood. The present study was designed to investigate the efficacy of two doses of dexmedetomidine as an adjuvant to ropivacaine and its protective effect against the neurotoxicity of las. Paw withdrawal thermal latency testing was used to detect the sensory blockade. extensor postural thrust testing was used to detect the motor blockade. The results demonstrated that the addition of dexmedetomidine to ropivacaine prolonged the duration of sensory and motor blockade in a dose-dependent manner compared with ropivacaine alone. Tunel staining was performed to examine apoptosis. Western blotting was used to detect the cleaved caspase-3 expression levels. The results showed that the addition of dexmedetomidine to ropivacaine decreased the rate of apoptosis and caspase-3 expression levels in a dose-dependent manner compared with ropivacaine alone (P<0.05). in addition, the rate of apoptosis and caspase-3 expression levels were significantly lower in the high-dose dexmedetomidine group compared with the low-dose dexmedetomidine group (P<0.05). The results suggested that the addition of dexmedetomidine to ropivacaine for sciatic nerve block in rats not only prolonged the duration of sensory and motor block of the sciatic nerve, but also markedly alleviated ropivacaine-induced neurotoxicity by decreasing caspase-3-dependent sciatic nerve cell apoptosis. Furthermore, the present study indicated that dexmedetomidine was more effective at a dose of 20 µg/kg compared with 6 µg/kg.

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

Cited by 34 publications

References 44 publications

Dexmedetomidine Attenuates Neuroinflammatory–Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway

Dexmedetomidine Attenuates Neuroinflammatory–Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway

Hypothermic properties of dexmedetomidine provide neuroprotection in rats following cerebral ischemia‑reperfusion injury

Effects of local dexmedetomidine administration on the neurotoxicity of ropivacaine for sciatic nerve block in rats

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