A Single Injection of N-Oleoyldopamine, an Endogenous Agonist for Transient Receptor Potential Vanilloid-1, Induced Brain Hypothermia, but No Neuroprotective Effects in Experimentally Induced Cerebral Ischemia in Rats

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Details zur Publikation

Autorinnen und Autoren: De Rink MMT, Naumann U, Kollmar R, Schwab S, Dietel B, Harada H, Tauchi M
Zeitschrift: Therapeutic Hypothermia and Temperature Management
Jahr der Veröffentlichung: 2019
ISSN: 2153-7658
eISSN: 2153-7933


Abstract

Targeted temperature management, or therapeutic hypothermia, is a potent neuroprotective approach after ischemic brain injury. Hypothermia should be induced as soon as possible after the onset of acute stroke to assure better outcomes. Accordingly, drugs with a fast-acting hypothermic effect sustainable through the period of emergency transportation to hospital would have clinical advantages. Activation of the transient receptor potential vanilloid-1 (TRPV1) can induce hypothermia. Our immunohistochemical investigations confirmed that TRPV1 was distributed to perivascular and periventricular regions of the rat brain, where TRPV1 can be easily detected by TRPV1 agonists. An endogenous TRPV1 selective agonist, N-oleoyldopamine (OLDA), and a synthetic antagonist, AMG 9810, were injected intraperitoneally into healthy adult male Wister rats, and brain and core temperatures and gross motor activities were monitored. Comparison with baseline temperatures showed that TRPV1 injection immediately induced mild hypothermia (p < 0.05 in brain and p < 0.01 in body), and AMG 9810 induced immediate mild hyperthermia (not significant). However, the OLDA-induced hypothermia did not decrease lesion volume after middle carotid artery occlusion in rats. Relative to vehicle, OLDA yielded poorer outcomes and AMG 9810 yielded better outcomes in neurological scores and lesion size. Our study showed that, as an agonist of TRPV1, OLDA has suitable hypothermia-inducing properties, but did not decrease lesion volume. Therefore, the search for novel TRPV1 agonists and/or antagonists providing hypothermia and neuroprotection should continue. Further investigations should also target OLDA-induced transient hypothermia combined with long-term hypothermia maintenance with surface cooling, which mimics the anticipated clinical use of this class of drug.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Dietel, Barbara
Graduiertenzentrum der FAU
Kollmar, Rainer Prof. Dr.
Medizinische Fakultät
Schwab, Stefan Prof. Dr.
Lehrstuhl für Neurologie


Einrichtungen weiterer Autorinnen und Autoren

Kurume University / 久留米大学


Zitierweisen

APA:
De Rink, M.M.T., Naumann, U., Kollmar, R., Schwab, S., Dietel, B., Harada, H., & Tauchi, M. (2019). A Single Injection of N-Oleoyldopamine, an Endogenous Agonist for Transient Receptor Potential Vanilloid-1, Induced Brain Hypothermia, but No Neuroprotective Effects in Experimentally Induced Cerebral Ischemia in Rats. Therapeutic Hypothermia and Temperature Management. https://dx.doi.org/10.1089/ther.2018.0036

MLA:
De Rink, Maria Mercedes Tejada, et al. "A Single Injection of N-Oleoyldopamine, an Endogenous Agonist for Transient Receptor Potential Vanilloid-1, Induced Brain Hypothermia, but No Neuroprotective Effects in Experimentally Induced Cerebral Ischemia in Rats." Therapeutic Hypothermia and Temperature Management (2019).

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Zuletzt aktualisiert 2019-19-06 um 08:23