Prostaglandin D2 DP1 receptor is beneficial in ischemic stroke and in acute exicitotoxicity in young and old mice.

Age
Abdullah Shafique AhmadSylvain Doré

Abstract

The cardiovascular complications reported to be associated with cyclooxygenase inhibitor use have shifted our focus toward prostaglandins and their respective receptors. Prostaglandin D(2) and its DP1 receptor have been implicated in various normal and pathologic conditions, but their role in stroke is still poorly defined. Here, we tested whether DP1 deletion aggravates N-methyl-D: -aspartic acid (NMDA)-induced acute toxicity and whether DP1 pharmacologic activation protects mice from acute excitotoxicity and transient cerebral ischemia. Moreover, since the elderly are more vulnerable to stroke-related damage than are younger patients, we tested the susceptibility of aged DP1 knockout (DP1(-/-)) mice to brain damage. We found that intrastriatal injection of 15 nmol NMDA caused significantly larger lesion volumes (27.2 +/- 6.4%) in young adult DP1(-/-) mice than in their wild-type counterparts. Additionally, intracerebroventricular pretreatment of wild-type mice with 10, 25, and 50 nmol of the DP1-selective agonist BW245C significantly attenuated the NMDA-induced lesion size by 19.5 +/- 5.0%, 39.6 +/- 7.7%, and 28.9 +/- 7.0%, respectively. The lowest tested dose of BW245C also was able to reduce middle cerebral artery occlusion...Continue Reading

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Citations

Oct 27, 2010·Translational Stroke Research·Muzamil Ahmad, Steven H Graham
Mar 3, 2012·Brain Research Bulletin·Reyna L VanGilderTaura L Barr
Jan 30, 2015·Frontiers in Molecular Neuroscience·Maria E Figueiredo-PereiraPeter Serrano
Mar 21, 2019·Sleep·Abdullah Shafique AhmadSylvain Doré
Jul 20, 2017·Npj Aging and Mechanisms of Disease·Antonio CurraisDavid Schubert
Jun 21, 2017·Proceedings of the National Academy of Sciences of the United States of America·Rahul VijayStanley Perlman
Aug 27, 2017·Scientific Reports·Abdullah Shafique AhmadSylvain Doré
Nov 10, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hiromichi Fujino
Jun 14, 2021·Molecular Neurobiology·Zeinab VahidiniaAbolfazl Azami Tameh

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