PGD(2) DP1 receptor protects brain from ischemia-reperfusion injury

The European Journal of Neuroscience
Sofiyan SaleemSylvain Doré

Abstract

Prostaglandin D(2) is the most abundant prostaglandin in the brain. It has long been described as a modulator of the neuroinflammatory process, but little is known regarding the role of its Galpha(s)-coupled receptor, DP1. Therefore, in this study, the effect of the DP1 receptor on the outcome of cerebral ischemia in wildtype (WT) and DP1 knockout (DP1(-/-)) C57Bl/6 mice was investigated. Ischemia-reperfusion injury was produced by a 90-min occlusion of the right middle cerebral artery followed by a 4-day reperfusion. Infarct size was 49.0 +/- 11.0% larger in DP1(-/-) mice (n = 11; P < 0.01) than in WT mice (n = 9 per group). However, no differences were detected in the relative cerebral blood flow (CBF) or any of the physiological parameters measured (n = 5 per group) or in the large blood vessel anatomy (n = 3 per group). To further address whether the DP1 protective role in the brain could be extended to neurons, mouse primary corticostriatal neuronal cultures were exposed to the DP1-selective agonist, BW245C, which provided dose-dependent protection against excitotoxicity induced by glutamate. Protection was significant at a dose as low as 0.05 microm. The results indicate that the DP1 receptor is neuroprotective in both in...Continue Reading

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Citations

Oct 27, 2010·Translational Stroke Research·Muzamil Ahmad, Steven H Graham
Jul 7, 2009·Experimental Neurology·Min ThuraKazuo Umemura
Feb 11, 2009·Journal of Neuroimmunology·Sofiyan SaleemSylvain Doré
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