Inhibition of phosphodiesterase IV enzyme improves locomotor and sensory complications of spinal cord injury via altering microglial activity: Introduction of Roflumilast as an alternative therapy

• Published in: International immunopharmacology 2020-09, Vol.86, p.106743-106743, Article 106743
• Main Authors: Moradi, Kamyar, Golbakhsh, Mohammadreza, Haghighi, Farinaz, Afshari, Khashayar, Nikbakhsh, Rajan, Khavandi, Mohammad Mahdi, Faghani, Shahriar, Badripour, Abolfazl, Etemadi, Ali, Ashraf-Ganjouei, Amir, Bagheri, Sayna, Dehpour, Ahmad Reza
• Format: Article
• Language: English
• Subjects: Anti-inflammatory agents; Biomarkers; cAMP; Chemical compounds; Complications; Cyclic AMP; IL-1β; Inflammation; Injury prevention; Interleukin 10; Locomotion; Microglia; Neuroinflammation; Pharmacology; Phosphodiesterase; Phosphodiesterase IV; Reagents; Rodents; Roflumilast; Sensitivity; Spinal cord injuries; Spinal cord injury (SCI); Spine; Tumor necrosis factor-α; Vertebrae
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106743

[Display omitted] •There is ongoing effort to discover an efficient approach for management of spinal cord injury (SCI) complications.•Roflumilast is able to alleviate locomotor and sensory complications of SCI.•Roflumilast is a highly selective inhibitor of phosphodiesterase 4 and can enhance the intracellular cAMP level.•Roflumilast decreases the relative ratio of pro-inflammatory (M1) to anti-inflammatory (M2) microglia in the lesion site.•Roflumilast attenuates the secondary damage of SCI through reducing the neuroinflammation. Despite the great search for an effective approach to minimize secondary injury in spinal cord injury (SCI) setting, there have been limited advances. Roflumilast is a selective inhibitor of phosphodiesterase 4 with potent anti-inflammatory properties. Here, we sought to explore Roflumilast efficacy in the improvement of locomotor and sensory deficits of SCI. In an animal setting, 50 male rats were randomly assigned to five groups: an SCI group receiving Placebo, three SCI groups receiving Roflumilast at the doses of 0.25, 0.5, and 1 mg/kg prior to T9 vertebra laminectomy, and a sham-operated group. Locomotor, mechanical, and thermal activities were evaluated for 28 days. At the end of the study, spinal cord samples were taken to assess the relative ratio of microglial subtypes, including M1 and M2, histopathological changes, levels of pro-inflammatory (TNF-α and IL-1β) and anti-inflammatory (IL-10) biomarkers, and cAMP level. Repeated measure analysis revealed significant effect for time-treatment interaction on locomotion [F (24, 270) = 280.7, p