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Roflumilast Reduces Cerebral Inflammation in a Rat Model of Experimental Subarachnoid Hemorrhage

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Abstract

Roflumilast, a selective inhibitor for PDE4, is approved by FDA as an anti-inflammation drug for treatment of chronic obstructive pulmonary disease (COPD). This study investigates the effects of roflumilast on cerebral inflammation in the rat SAH model. Here, we show that subcutaneous administration of roflumilast (3 mg/kg) significantly improved the neurological deficits. Measurement of evans blue extravasation and brain water content revealed a significant reduction of blood-brain barrier permeability and brain edema. Importantly, roflumilast treatment remarkably decreased levels of IL-1β, IL-6, and TNF-α and the number of apoptotic neurons in the brain after SAH. These results indicate that roflumilast is effective in treating cerebral inflammation following SAH.

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Acknowledgments

This work was supported by funds from the National Natural Science Foundation of China (Grant No. 81471212, 81271275, 81070947 to Baoliang Sun; 81671141 to Zongyong Zhang) and the Natural Science Foundation of Shandong, China (Grant No. ZR2012HZ006 to Baoliang Sun).

Contributors

BS and JK conceived the project and designed experiments. QW, LQ, HL, LM, MY, RX, and XY performed the experiments; BS and JW analyzed the results, ZZ and BS wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zongyong Zhang, Jiming Kong or Baoliang Sun.

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The authors declare that they have no conflict of interest

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Qingjian Wu and Lifeng Qi are co-first authors.

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Wu, Q., Qi, L., Li, H. et al. Roflumilast Reduces Cerebral Inflammation in a Rat Model of Experimental Subarachnoid Hemorrhage. Inflammation 40, 1245–1253 (2017). https://doi.org/10.1007/s10753-017-0567-8

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  • DOI: https://doi.org/10.1007/s10753-017-0567-8

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