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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Journal

Journal ID (nlm-journal-id): 7600105

Journal ID (pubmed-jr-id): 4229

Journal ID (nlm-ta): Inflammation

Journal ID (iso-abbrev): Inflammation

Title: Inflammation

ISSN (Print): 0360-3997

ISSN (Electronic): 1573-2576

Publication date Nihms-submitted: 10 October 2018

Publication date (Print): August 2017

Publication date PMC-release: 18 October 2018

Volume: 40

Issue: 4

Pages: 1245-1253

Affiliations

[1 ]Department of Neurology, Shandong University School of Medicine, Jinan, Shandong 250012, China

[2 ]Department of Neurology, Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000, China

[3 ]Department of Emergency, Jining NO.1 People’s Hospital, Jining, Shandong 272011, China

[4 ]Department of Neurology, Liaocheng People’s Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, 252000, China

[5 ]Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA

[6 ]Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB R3E 0J9, Canada

Author notes

[7 ]To whom correspondence should be addressed to Zongyong Zhang at Department of Neurology, Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000, China. zongyongzhanghust@ 123456163.com ; and to Jiming Kong at Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB R3E 0J9, Canada. Jiming.Kong@ 123456umanitoba.ca ; and Baoliang Sun at Department of Neurology, Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000, China. blsun88@ 123456163.com

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.

Article

Accession ID: PMC6193485 Pmcid ID: PMC6193485 Pmc-uid ID: 6193485 Manuscript ID: nihpa991741

DOI: 10.1007/s10753-017-0567-8

PMC ID: 6193485

PubMed ID: 28451841

SO-VID: 5c60af8a-1dec-4956-bc4f-78c3360d4bd0

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