Exp Neurobiol.  2017 Oct;26(5):278-286. 10.5607/en.2017.26.5.278.

Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats

Affiliations
  • 1Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Sungkyunkwan University (SKKU), Suwon 16419, Korea. jhkim74@skku.edu
  • 2Department of Biomedical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Korea.
  • 3Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Korea. jelee@yuhs.ac
  • 4BK21 PLUS Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea.
  • 5Division of Rheumatology, Department of Internal Medicine, Institute for Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul 03722, Korea.

Abstract

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206+ & ED1+ cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype.

Keyword

Agmatine; Spinal cord injury; Macrophage; M2 polarization; Neuroinflammation
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