Effects of delta-opioid receptor stimulation and inhibition on hippocampal survival in a rat model of forebrain ischaemia

Iwata, Makoto; Inoue, Satoki; Kawaguchi, Maiko; Nakamura, Mitsutoshi; Konishi, Noboru; Furuya, Hitoshi

doi:10.1093/bja/aem220

Cited by 43 publications

(34 citation statements)

References 36 publications

(18 reference statements)

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“…rat model. 27 Studies have also shown that d-opioid receptor activation attenuates oxidative injuries in the brain exposed to ischemia/reperfusion by enhancing antioxidant ability and inhibition of caspase activity. 28 Moreover, d-opioid receptors have been involved in neuroprotective mechanisms of Alzheimer 29 and Parkinson's 30 diseases.…”

Section: Discussionmentioning

confidence: 99%

Delta-Opioid Agonist SNC-121 Protects Retinal Ganglion Cell Function in a Chronic Ocular Hypertensive Rat Model

Abdul

Akhter²,

Husain³

2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. This study examined if the delta-opioid (d-opioid) receptor agonist, SNC-121, can improve retinal function and retinal ganglion cell (RGC) survival during glaucomatous injury in a chronic ocular hypertensive rat model. METHODS.IOP was raised in brown Norway rats by injecting hypertonic saline into the limbal venous system. Rats were treated with 1 mg/kg SNC-121 (intraperitoneally [IP]) once daily for 7 days. Pattern-electroretinograms (PERGs) were obtained in response to contrast reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde labeling. Expression of TNF-a and p38 mitogen-activated protein (MAP) kinase was measured by immunohistochemistry and Western blotting.RESULTS. PERG amplitudes in ocular hypertensive eyes were significantly reduced (14.3 6 0.60 lvolts) when compared with healthy eyes (18.0 6 0.62 lvolts). PERG loss in hypertensive eyes was inhibited by SNC-121 treatment (17.20 6 0.1.3 lvolts; P < 0.05). There was a 29% loss of RGCs in the ocular hypertensive eye, which was inhibited in the presence of SNC-121. TNF-a production and activation of p38 MAP kinase in retinal sections and optic nerve samples were upregulated in ocular hypertensive eyes and inhibited in the presence of SNC-121. Furthermore, TNF-a induced increase in p38 MAP kinase activation in astrocytes was inhibited in the presence of SNC-121.CONCLUSIONS. These data provide evidence that activation of dopioid receptors inhibited the loss of PERG amplitudes and rate of RGC loss during glaucomatous injury. Mechanistic data provided clues that TNF-a is mainly produced from glial cells and activates p38 MAP kinase, which was significantly inhibited by SNC-121 treatment. Overall, data indicate that enhancement of d-opioidergic activity in the eye may provide retina neuroprotection against glaucoma. (Invest Ophthalmol Vis Sci.

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Section: Discussionmentioning

confidence: 99%

Delta-Opioid Agonist SNC-121 Protects Retinal Ganglion Cell Function in a Chronic Ocular Hypertensive Rat Model

Abdul

Akhter²,

Husain³

2013

Invest. Ophthalmol. Vis. Sci.

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“…DADLE induces hibernation in ground squirrels in situations were κ and μ agonists have failed [46]. It has also been reported that DADLE treatment protects the brain against focal [48] and global cerebral ischemia [49][50][51], making DADLE a promising neuroprotective candidate.…”

Section: Opioid Receptor Activatorsmentioning

confidence: 99%

“…Two features distinguish DADLE: hibernation induction [46,47] and neuroprotective effects [48][49][50]. DADLE induces hibernation in ground squirrels in situations were κ and μ agonists have failed [46].…”

Section: Opioid Receptor Activatorsmentioning

confidence: 99%

“…However, Iwata and colleagues reported that DADLE failed to protect rat brains against global ischemia when the temperature was maintained at 37.5 ± 0.5 °C by surface heating, suggesting that hypothermia is essential for the effect [54]. Iwata and colleagues also reported that DADLE only provided limited neuroprotection to relatively ischemiaresistant regions and not to selectively vulnerable regions [49].…”

Section: Opioid Receptor Activatorsmentioning

confidence: 99%

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Drug-Induced Hypothermia in Stroke Models: Does it Always Protect?

Zhang¹,

Wang²,

Zhao³

et al. 2013

CNSNDDT

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Ischemic stroke is a common neurological disorder lacking a cure. Recent studies show that therapeutic hypothermia is a promising neuroprotective strategy against ischemic brain injury. Several methods to induce therapeutic hypothermia have been established; however, most of them are not clinically feasible for stroke patients. Therefore, pharmacological cooling is drawing increasing attention as a neuroprotective alternative worthy of further clinical development. We begin this review with a brief introduction to the commonly used methods for inducing hypothermia; we then focus on the hypothermic effects of eight classes of hypothermia-inducing drugs: the cannabinoids, opioid receptor activators, transient receptor potential vanilloid, neurotensins, thyroxine derivatives, dopamine receptor activators, hypothermia-inducing gases, adenosine, and adenine nucleotides. Their neuroprotective effects as well as the complications associated with their use are both considered. This article provides guidance for future clinical trials and animal studies on pharmacological cooling in the setting of acute stroke. KeywordsBrain ischemia; Hypothermic; Neuroprotection; Pharmacological cooling Send correspondence to: Dr. Feng Zhang, Department of Neurology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, PA, 15213, USA, Telephone: 412-383-7604, Fax: 412-648-1239, zhanfx2@upmc.edu NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 1. Hypothermia and strokes IntroductionTherapeutic hypothermia is defined as a 2-6°C reduction of core body temperature [1][2][3] and is a promising neuroprotective approach against brain injury induced by strokes. In hemorrhagic stroke, hypothermia reduces brain edema [4,5] and improves neurologic function [4][5][6][7]. In ischemic stroke, hypothermia is also protective, which has been proven in randomized clinical trials in human cardiac arrest and in animal studies of focal and global ischemia [8,9]. However, the impact of hypothermia on patients with acute ischemic stroke still needs to be explored [10]. During the past decades, studies on hypothermia and ischemic stroke have suggested that the required amplitude of protective hypothermia depends on its time of initiation relative to stroke onset, duration, and depth of hypothermia [1,9,11]. Optimal protection is typically gained when hypothermia is induced as early as possible after stroke onset, with a mild-to-moderate hypothermia of 32 to 35°C that lasts at least one to two hours [1, 2, 12-14]. Protective mechanism of hypothermia in ischemic strokeAlthough hypothermia is effective in protecting against experimental models of ischemic stroke, the precise protective mechanisms are not yet fully understood. It has been suggested that the protective mechanisms are multifold, including reductions in metabolic rate, cerebral blood flow, blood-brain barrier damage, as well as decreases in excitotoxicity, apoptosis, inflammation and free radical production [15]. On average, hypothermia red...

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“…Cet effet protecteur a été élargi au muscle et au coeur [5, 48,86]. De plus, le récepteur delta est associé à la survie et à la différenciation neuronale, à la neurogenèse et, plus particulièrement, à la survie des neurones de l'hippocampe et à la mémoire spatiale [24].…”

Section: Récepteur Deltaunclassified

The delta opioid receptor: a novel therapeutic target for pain and even more...

Gavériaux‐Ruff

2009

Douleur analg

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REVUE DE LA LITTÉRATURE / LITERATURE REVIEW DOSSIER Le récepteur opioïde delta : une nouvelle cible thérapeutique pour la douleur mais plus encore… The delta opioid receptor: a novel therapeutic target for pain and even more… C. Gaveriaux-Ruff Reçu le 31 août 2009 ; accepté le 4 septembre 2009 © Springer-Verlag France 2009 Résumé Le récepteur opioïde delta constitue une nouvelle cible pour le traitement de la douleur. Il est différent du récepteur opioïde mu, car il est peu efficace en nociception aiguë, mais devient plus actif dans les situations pathologiques. L'intérêt pour ce récepteur s'est accru récemment avec l'identification de nouveaux ligands et l'étude de son trafic intracellulaire. De plus, l'activation du récepteur delta diminue les manifestations d'anxiété et de dépression. Dans cette revue sont présentées les données récentes sur les propriétés analgésiques et les autres effets des agonistes opioïdes delta. Mots clés Récepteur opioïde · Delta · Douleur chronique · Anxiété dépressionAbstract The delta opioid receptor is a novel target for pain treatment. The delta receptor appears different from the mu receptor as it is poorly effective for acute nociception but becomes more active in pathological situations. The interest for this receptor has increased recently with the identification of novel ligands and the study of its intracellular traffic. In addition, delta receptor activation lowers anxiety and depression. This review presents the recent knowledge on delta opioid analgesia and on the other neurobiological effects of delta receptor activation.

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Effects of delta-opioid receptor stimulation and inhibition on hippocampal survival in a rat model of forebrain ischaemia

Cited by 43 publications

References 36 publications

Delta-Opioid Agonist SNC-121 Protects Retinal Ganglion Cell Function in a Chronic Ocular Hypertensive Rat Model

Delta-Opioid Agonist SNC-121 Protects Retinal Ganglion Cell Function in a Chronic Ocular Hypertensive Rat Model

Drug-Induced Hypothermia in Stroke Models: Does it Always Protect?

The delta opioid receptor: a novel therapeutic target for pain and even more...

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