Document Type
Article
Publication Date
8-8-2014
Abstract
PURPOSE: The first genomewide association study indicated that variations in the phosphodiesterase 4D (PDE4D) gene confer risk for ischemic stroke. However, inconsistencies among the studies designed to replicate the findings indicated the need for further investigation to elucidate the role of the PDE4 pathway in stroke pathogenesis. Hence, we studied the effect of global inhibition of the PDE4 pathway in two rat experimental stroke models, using the PDE4 inhibitor rolipram. Further, the specific role of the PDE4D isoform in ischemic stroke pathogenesis was studied using PDE4D knockout rats in experimental stroke. METHODS: Rats were subjected to either the ligation or embolic stroke model and treated with rolipram (3mg/kg; i.p.) prior to the ischemic insult. Similarly, the PDE4D knockout rats were subjected to experimental stroke using the embolic model. RESULTS: Global inhibition of the PDE4 pathway using rolipram produced infarcts that were 225% (pCONCLUSIONS: Despite increase in infarct size after global inhibition of the PDE4 pathway with rolipram, specific inhibition of the PDE4D isoform had no effect on experimental stroke. These findings support a role for the PDE4 pathway, independent of the PDE4D isoform, in ischemic stroke pathogenesis.
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Recommended Citation
Yang F, Sumbria RK, Xue D, et al. Effects of PDE4 pathway inhibition in rat experimental stroke. J Pharm Pharm Sci. 2014;17(3):362-70. https://doi.org/10.18433/J3S02V
Copyright
The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution-Share Alike 4.0 License.
Included in
Animal Experimentation and Research Commons, Medical Neurobiology Commons, Nervous System Diseases Commons, Other Chemicals and Drugs Commons, Other Pharmacy and Pharmaceutical Sciences Commons, Pharmaceutical Preparations Commons, Therapeutics Commons
Comments
This article was originally published in Journal of Pharmacy and Pharmaceutical Sciences, volume 17, issue 3, in 2014. https://doi.org/10.18433/J3S02V