The adenosine A 2A receptor antagonist SCH58261 reduces macrophage/microglia activation and protects against experimental autoimmune encephalomyelitis in mice

• Published in: Neurochemistry international Vol. 129; p. 104490
• Main Authors: Chen, Yu, Zhang, Zheng-Xue, Zheng, Liu-Pu, Wang, Li, Liu, Yin-Feng, Yin, Wei-Yong, Chen, Yan-Yan, Wang, Xin-Shi, Hou, Sheng-Tao, Chen, Jiang-Fan, Zheng, Rong-Yuan
• Format: Journal Article
• Language: English
• Published: England 01.10.2019
• Subjects: Adenosine A2 Receptor Antagonists - administration & dosage; Adenosine A2 Receptor Antagonists - pharmacology; Adenosine A2 Receptor Antagonists - therapeutic use; Animals; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Down-Regulation - drug effects; Drug Administration Schedule; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - etiology; Encephalomyelitis, Autoimmune, Experimental - pathology; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Female; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Macrophage Activation - drug effects; Mice; Mice, Inbred C57BL; Microglia - drug effects; Microglia - physiology; Myelin Sheath - pathology; Myelin-Oligodendrocyte Glycoprotein - immunology; Myelin-Oligodendrocyte Glycoprotein - toxicity; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Nitric Oxide Synthase Type II - biosynthesis; Nitric Oxide Synthase Type II - genetics; Peptide Fragments - immunology; Peptide Fragments - toxicity; Pyrimidines - administration & dosage; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Quadriplegia - etiology; Receptors, Adrenergic, alpha-2 - drug effects; Receptors, Adrenergic, alpha-2 - physiology; Spinal Cord - drug effects; Spinal Cord - pathology; Triazoles - administration & dosage; Triazoles - pharmacology; Triazoles - therapeutic use; Neurobehavioral deficit; Multiple sclerosis; Therapeutic time window; Experimental autoimmune encephalomyelitis; Macrophage/microglia; A(2A) adenosine receptor
• ISSN: 1872-9754

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS) affecting more than 2.5 million individuals worldwide. In the present study, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) mice were treated with adenosine receptor A antagonist SCH58261 at different periods of EAE development. The administration of SCH58261 at 11-28 days post-immunization (d.p.i.) with MOG improved the neurological deficits. This time window corresponds to the therapeutic time window for MS treatment. SCH58261 significantly reduced the CNS neuroinflammation including reduced local infiltration of inflammatory cells, demyelination, and the numbers of macrophage/microglia in the spinal cord. Importantly, SCH58261 ameliorated the EAE-induced neurobehavioral deficits. By contrast, the SCH58261 treatment was ineffective when administered at the beginning of the onset of EAE (i.e., 1-10 d.p.i). The identification of the effective therapeutic window of A receptor antagonist provide insight into the role of A receptor signaling in EAE, and support SCH58261 as a candidate for the treatment of MS in human.