Effects of PDE4 Pathway Inhibition in Rat Experimental Stroke

Authors

  • Fan Yang Departments of Anatomy & Neurobiology, School of Pharmacy, Keck Graduate Institute, Claremont, California
  • Rachita K Sumbria Neurology, and Department of Biopharmaceutical Sciences, School of Pharmacy, Keck Graduate Institute, Claremont, California
  • Dong Xue Neurology, School of Pharmacy, Keck Graduate Institute, Claremont, California
  • Chuanhui Yu Neurology, School of Pharmacy, Keck Graduate Institute, Claremont, California
  • Dan He Neurology, School of Pharmacy, Keck Graduate Institute, Claremont, California
  • Shuo Liu Departments of Anatomy & Neurobiology, School of Pharmacy, Keck Graduate Institute, Claremont, California
  • Annlia Paganini-Hill Neurology, School of Pharmacy, Keck Graduate Institute, Claremont, California
  • Mark Fisher Departments of Anatomy & Neurobiology, Neurology, and Pathology & Laboratory Medicine, University of California, Irvine, California, School of Pharmacy, Keck Graduate Institute, Claremont, California

DOI:

https://doi.org/10.18433/J3S02V

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% (p<0.01) and 138% (p<0.05) of control in the ligation and embolic models, respectively. PDE4D knockout rats subjected to embolic stroke showed no change in infarct size compared to wild-type control. CONCLUSIONS: 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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Author Biography

Mark Fisher, Departments of Anatomy & Neurobiology, Neurology, and Pathology & Laboratory Medicine, University of California, Irvine, California, School of Pharmacy, Keck Graduate Institute, Claremont, California

Professor of Neurology, Anatomy & Neurobiology, and Pathology & Laboratory Medicine, UC Irvine School of Medicine

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Published

2014-08-08

How to Cite

Yang, F., Sumbria, R. K., Xue, D., Yu, C., He, D., Liu, S., … Fisher, M. (2014). Effects of PDE4 Pathway Inhibition in Rat Experimental Stroke. Journal of Pharmacy & Pharmaceutical Sciences, 17(3), 362–370. https://doi.org/10.18433/J3S02V

Issue

Section

Pharmaceutical Sciences; Review Articles