Neuroprotection by the α2-Adrenoreceptor Agonist Dexmedetomidine in a Focal Model of Cerebral Ischemia

Maier, Carolina M.; Steinberg, Gary K.; Sun, Guo Hua; Zhi, Guo; Maze, Mervyn

doi:10.1097/00000542-199308000-00016

Cited by 218 publications

(118 citation statements)

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“…DEX attenuates the ischemia-induced excessive NA release by activating presynaptic α 2 -ARs (38,39), which may lead to the formation of free radicals (40). In addition, the protective action of α 2 -AR agonists may be due to a postsynaptic reduction in neuronal excitability and/or a possible presynaptic decrease in glutamate release (41)(42)(43)(44), which is linked to the suppression of voltage-dependent Ca 2+ channels and mitogen-activated protein kinase activity (42).…”

Section: Transmitter Releasementioning

confidence: 99%

Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury (Review)

Cai

Jia

et al. 2014

Molecular Medicine Reports

117

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Abstract. Dexmedetomidine (DEX), a highly specific α 2 -adrenergic agonist, which exhibits anaesthetic-sparing, analgesia and sympatholytic properties. DEX modulates gene expression, channel activation, transmitter release, inflammatory processes and apoptotic and necrotic cell death. It has also been demonstrated to have protective effects in a variety of animal models of ischemia/reperfusion (I/R) injury, including the intestine, myocardial, renal, lung, cerebral and liver. The broad spectrum of biological activities associated with DEX continues to expand, and its diverse effects suggest that it may offer a novel therapeutic approach for the treatment of human diseases with I/R involvement.

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Section: Transmitter Releasementioning

confidence: 99%

Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury (Review)

Cai

Jia

et al. 2014

Molecular Medicine Reports

117

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“…Dexmedetomidine was another agent searched in our study which has an alpha-2 adrenoceptor agonist effect and its effect on preventing I/R injury on several brain and heart I/R models were via decreasing the cathecolamine release during the ischemia period [5,6,30]. Hoffman et al have produced cerebral ischemia on rat brain model and observed that the neurological and histopathological results on the dexmedetomidine group was better than the control group and this effect was returned by using alpha-2 adrenoceptor antagonists [31].…”

Section: Discussionmentioning

confidence: 99%

“…Its proven that each molecule of propofol can scavange two free radicals and prevent the lipid peroxidation inducted by oxidative stress [3,4]. The alfa 2 adrenoreceptor agonist dexmedetomidin used as an anxiolytic and sedative agent in intensive care units decreases the cathecolamine decharge inducted by ischemia and decreases the damage caused by reperfusion [5,6].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Dexmedetomidine and Propofol on Oxidative Stress and Antioxidizing System Studied on Liver Ischemia-reperfusion Model on Rats

Urfalıoğlu¹,

Cantürk²,

Akçaboy³

et al. 2013

J Anesthe Clinic Res

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Surgical procedureAnesthesia was induced with Ketamine to rats, (Ketalar flk, Eczacıbaşı) with a dose of 90 mg/kg. Under sterile cover, laporatomy was performed via midline incision. Hepatoduodenal ligament was Materials and methods: 24 rats were randomly divided into four groups. Following anesthesia laparotomy was done and hepatoduodenal ligament was explorated. Tissue samples were taken for both biochemical (MDA, SOD, GPx) and histological study.Results: MDA level was hisghest in Group II and was significantly lower in Group III and Group IV. GPx level was lowest in Group II, the level of GPx was higher in Group III and Group IV with respect to Group II. SOD level was lowest in Group II and was highest in Group IV. SOD levels in Group II and Group III did not show statistical significance. In the histopathological study, in Group I the liver parenchyme and membrane integrity was protected; in Group II the hepatocyte cellular membrane integrity was distorted, microvesicule number increased and the liver sinusoids were shrunken; in Group III the hepatocyte membrane and nucleus was near normal and well protected; and in Group IV the cellular component structures were protected, hepatocyte cell membrane was protected in normal thickness. Discussion:The results show that dexmedetomidine and propofol decrease the level of MDA in similarly; the effect of dexmedetomidine on GPx level was slightly lower than propofol and its effect on SOD level was lower than propofol. As a result, we believe that either propofol or dexmedetomidine can be effective in protecting hepatocytes from I/R injury especially in log term procedures but the former drug having dominance in this protective role.

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“…Dexmedetomidine and clonidine have a neuroprotective effect in animal models of focal cerebral ischemia [368][369][480][481], transient global ischemia [482], and hypoxicischemic brain injury in neonates [483]. Since dexmedetomidine is effective as a neuroprotectant even when the extracellular concentrations of glutamate and noradrenaline are not reduced [368], and since it appears to cause transactivation in astrocytes [119], its neuroprotective effect might be due to a paracrine action of released growth factor on adjacent neurons [117] as suggested in (Fig.…”

Section: Brain Ischemiamentioning

confidence: 99%

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders?

Hertz¹,

Chen²,

Gibbs³

et al. 2004

CDTCNSND

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Considerable attention has recently been paid to astrocyte functions, which are briefly summarized. A large amount of data is available about adrenoceptor expression and function in astrocytes, some of it dating back to the 1970's and some of it very recent. This material is reviewed in the present paper. The brain is innervated by noradrenergic fibers extending from locus coeruleus in the brain stem, which in turn is connected to a network of adrenergic and noradrenergic nuclei in the medulla and pons, contributing to the control of (nor)adrenergic, serotonergic, dopaminergic and cholinergic function, both in the central nervous system (CNS) and in the periphery. In the CNS astrocytes constitute a major target for noradrenergic innervation, which regulates morphological plasticity, energy metabolism, membrane transport, gap junction permeability and immunological responses in these cells. Noradrenergic effects on astrocytes are essential during consolidation of episodal, long-term memory, which is reinforced by β-adrenergic activation. Glycogenolysis and synthesis of glutamate and glutamine from glucose, both of which are metabolic processes restricted to astrocytes, occurs at several time-specific stages during the consolidation. Astrocytic abnormalities are almost certainly important in the pathogenesis of multiple sclerosis and in all probability contribute essentially to inflammation and malfunction in Alzheimer's disease and to mood disturbances in affective disorders. Noradrenergic function in astrocytes is severely disturbed by chronic exposure to cocaine, which also changes astrocyte morphology. Development of drugs modifying noradrenergic receptor activity and/or down-stream signaling is advocated for treatment of several neurological/psychiatric disorders and for neuroprotection. Astrocytic preparations are suggested for study of mechanism(s) of action of antidepressant drugs and pathophysiology of mood disorders.

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Neuroprotection by the α2-Adrenoreceptor Agonist Dexmedetomidine in a Focal Model of Cerebral Ischemia

Cited by 218 publications

References 0 publications

Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury (Review)

Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury (Review)

The Effect of Dexmedetomidine and Propofol on Oxidative Stress and Antioxidizing System Studied on Liver Ischemia-reperfusion Model on Rats

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders?

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