Endothelin B receptor agonist, IRL-1620, provides long-term neuroprotection in cerebral ischemia in rats

Brain Research
Mary G LeonardA Gulati

Abstract

We have earlier shown that stimulation of endothelin B receptors by IRL-1620 provides significant neuroprotection at 24h following cerebral ischemia. However, the effect of IRL-1620 is not known in the subacute phase of cerebral ischemia, where development of cerebral edema further contributes towards brain damage. This study was designed to determine the effect of IRL-1620 on neurological functions, infarct volume, oxidative stress, and endothelin receptors following permanent middle cerebral artery occlusion for 7 days. Rats received three intravenous injections of either vehicle or IRL-1620 [Suc-[Glu9,Ala11,15]-Endothelin-1(8-12)] at 2, 4, and 6h post occlusion. Treatment with IRL-1620 reduced infarct volume (54.06 ± 14.12 mm(3) vs. 177.06 ± 13.21 mm(3)), prevented cerebral edema and significantly improved all neurological and motor function parameters when compared to the vehicle-treated group. Vehicle-treated middle cerebral artery occluded rats demonstrated high levels of malondialdehyde and low levels of reduced glutathione and superoxide dismutase; these effects were reversed in IRL-1620 treated rats. No change in expression of endothelin A receptor was observed 7 days after induction of cerebral ischemia in vehicle or ...Continue Reading

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Citations

Mar 10, 2016·Pharmacological Reviews·Anthony P DavenportJanet J Maguire
Jan 6, 2016·Indian Journal of Pharmacology·Anil Gulati
Aug 19, 2014·British Journal of Pharmacology·J J Maguire, A P Davenport
Oct 8, 2014·Archivum Immunologiae Et Therapiae Experimentalis·Agata KowalczykAnna Goraca
May 13, 2014·Brain & Development·Bhagya PuppalaAnil Gulati
May 3, 2016·Progress in Neurobiology·Stéphanie HostenbachJacques De Keyser
Sep 11, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Marilyn J CipollaSiu-Lung Chan
Jun 24, 2020·Canadian Journal of Physiology and Pharmacology·Amaresh K RanjanAnil Gulati
May 1, 2021·International Journal of Molecular Sciences·Yutaka Koyama

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