Neuroprotective Effects of Dexmedetomidine in the Gerbil Hippocampus after Transient Global Ischemia

Kuhmonen, Johanna; Pokorný, J; Miettinen, Reijo; Haapalinna, Antti; Jolkkonen, Jukka; Riekkinen, Paavo; Sivenius, Juhani

doi:10.1097/00000542-199708000-00025

Cited by 137 publications

(91 citation statements)

References 18 publications

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“…DEX prevented delayed neuronal death in the CA3 area and the dentate hilus in the gerbil hippocampus when administered prior to and following the induction of ischemia. Low doses of DEX (3 µg/kg) provided potent neuroprotective effects against cerebral ischemia (86). Co-administration of lidocaine and DEX improved the neurological outcome without the alteration of glutamate and NA levels during forebrain ischemia in rats (87).…”

Section: Cerebral Injurymentioning

confidence: 97%

See 1 more Smart Citation

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

Cai

Jia

et al. 2014

Molecular Medicine Reports

110

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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: Cerebral Injurymentioning

confidence: 97%

“…An increasing number of in vitro and in vivo studies indicates that DEX also exerts a cell-protective effect on nervous tissue under ischemic conditions (16,35,(85)(86)(87)(88). The relative safety of DEX administered as a sedative agent to neonatal animals was associated with the development of hippocampal synaptic functions.…”

Section: Cerebral Injurymentioning

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

110

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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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“…They explained these regional differences by the relative distribution and terminal fields of noradrenergic fibers within the different subfields of the hippocampus (16). The noradrenergic afferents arising from the locus cerulous form a dense network within the hilus of the DG and in the stratum lucidum of the CA3 area (26).…”

Section: Kose Ea Et Al: Effects Of Intracisternal Dexmedetomidine Onmentioning

confidence: 99%

“…It has been reported that the addition of dexmedetomidine to local anesthetic solution in intravenous regional anesthesia improved the quality of anesthesia and decreased the analgesic requirements (5,20). There is evidence that systemic administration of dexmedetomidine may partially prevent neuronal damage in some models of brain ischemia and this neuroprotective effect is mediated by the activation of the α₂-adrenergic receptors (8,9,(15)(16)(17). On the other hand, it has been shown by Konakci et al.…”

Section: Introductionmentioning

confidence: 99%

Effects of intracisternal dexmedetomidine on cerebral neuronal cells in rat: a preliminary study

Kose¹,

Bakar²,

Kasımcan³

et al. 2012

Turkish Neurosurgery

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AIm:The aim was to investigate whether dexmedetomidine had a toxic effect on cerebral neurons when it was administered centrally into the cerebrospinal fluid by the intracisternal route. mAterIAl and methOds: Eighteen rats were anesthetized and the right femoral artery was cannulated. Mean arterial pressures, heart rates, arterial carbon dioxide tension, arterial oxygen tension, and blood pH were recorded. When the free cerebrospinal fluid flow was seen, 0.1 ml normal saline (Group SIC, n=6) or 9 µg/kg diluted dexmedetomidine in 0.1 ml volume (Group DIC, n=6) was administered into the cisterna magna of rats. After 24 hours, the whole body blood was collected for measurement of plasma lipid peroxidation (LPO) levels. The hippocampal formations used for histopathological examination and measurement of tissue LPO levels.results: There was a statistically significant difference between the DIC/SIC groups and DIC/CONTROL groups regarding the brain LPO levels (p=0.002, p<0.001, respectively). Plasma LPO levels were statistically different between the CONTROL/DIC groups, CONTROL/SIC groups, DIC/ SIC groups (p=0.002, p=0.047, p=0.025, respectively), The picnotic neuron counts were different between the CONTROL/SIC groups, CONTROL/ DIC groups, DIC/SIC groups (p<0.001, p=0.001, p=0.024, respectively). COnClusIOn:In conclusion, dexmedetomidine had a toxic effect on cerebral neurons when it was administered centrally into the cerebrospinal fluid by the intracisternal route.KeywOrds: Dexmedetomidine, Intracisternal, Intrathecal, Hippocampus, Brain, Cerebral neuron ÖZ AmAÇ: İntrasisternal olarak serebrospinal sıvı içine santral yolla verilen deksmedetomidinin serebral nöronlar üzerinde toksik etkisinin olup olmadığını araştırmak amaçlandı. yÖntem ve GereÇler: On sekiz sıçana anestezi verildikten sonra sağ femoral arterleri kanülize edildi. Ortalama arter basınçları, kalp hızları, arteriyal karbon dioksit basınçları, arteriyal oksijen basınçları, kan pH değerleri kaydedildi. Serbest serebrospinal sıvı akışı görüldükten sonra ratların sisterna magnaları içine 0,1 ml serum fizyolojik (Grup SIC, n=6) veya 0,1 ml volüm içinde 9 µg/kg sulandırılmış deksmedetomidin (Grup DIC, n=6) verildi. Yirmi dört saat sonra lipid peroksidasyon (LPO) seviyesi ölçümleri için tüm vücut kanı toplandı. Histopatolojik inceleme ve doku LPO seviyesi ölçümleri için hipokampüs kullanıldı.BulGulAr: Beyin dokusu LPO seviyeleri yönünden DIC/SIC ve DIC/CONTROL grupları arasında istatistiksel belirgin farklılık vardı (sırasıyla, p=0.002, p<0.001). Plazma LPO seviyeleri CONTROL/DIC, CONTROL/SIC, DIC/SIC grupları arasında istatistiksel olarak farklıydı (sırasıyla, p=0,002, p=0,047, p=0,025). Piknotik nöron sayıları CONTROL/SIC, CONTROL/ DIC, DIC/SIC grupları arasında istatiksel olarak farklıydı (sırasıyla, p<0,001, p=0,001, p=0,024). sOnuÇ: Sonuç olarak, intrasisternal olarak serebrospinal sıvı içine santral yolla verilen deksmedetomidinin serebral nöronlar üzerine toksik etkisi olduğu görüldü.

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Neuroprotective Effects of Dexmedetomidine in the Gerbil Hippocampus after Transient Global Ischemia

Cited by 137 publications

References 18 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)

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

Effects of intracisternal dexmedetomidine on cerebral neuronal cells in rat: a preliminary study

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