Idazoxan attenuates spinal cord injury by enhanced astrocytic activation and reduced microglial activation in rat experimental autoimmune encephalomyelitis.
Idazoxan, an imidazoline 2 receptor (I(2)R) ligand, has been shown to protect against brain injury in several animal models of neurological disorders. In the present study we investigated the effect of idazoxan on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced by immunizing Wistar rats with guinea pig spinal cord homogenates emulsified in CFA, followed by daily treatment of idazoxan (0, 0.5 mg/kg, 1.5 mg/kg, 4.5 mg/kg, i.p, bid) for 10 days. The results showed that the treatment of idazoxan (1.5 mg/kg and 4.5 mg/kg) significantly decreased the incidence and alleviated inflammatory cell infiltration and demyelination in spinal cords and cerebral cortex. Furthermore, the protective effect of idazoxan on EAE was associated with the enhanced astrocytic activation and attenuated microglial activation and with the subsequent down-regulated expression of proinflammatory cytokines IL-12p40 and IFN-gamma and up-regulated expression of anti-inflammatory cytokines IL-10 and TGF-beta(1). Thus, the daily treatment of the I(2)R ligand idazoxan for 10 days attenuates EAE pathology by differential modulation of astrocytic and microglial activations, raising a possibility that the I(2)R ligand may be a novel strategy for treating EAE.
Wang
Xin-Shi
XS
Department of Neurology, the First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, Wenzhou City, Zhejiang, PR China.
Chen
Yan-Yan
YY
Shang
Xiao-Feng
XF
Zhu
Zhen-Guo
ZG
Chen
Guo-Qian
GQ
Han
Zhao
Z
Shao
Bei
B
Yang
Hui-Min
HM
Xu
Hui-Qin
HQ
Chen
Jiang-Fan
JF
Zheng
Rong-Yuan
RY
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003711:Demyelinating Diseases / Q000188:drug therapy; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D005786:Gene Expression Regulation; D019329:Idazoxan / Q000627:therapeutic use*; D054755:Imidazoline Receptors / Q000819:agonists / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D054755:Imidazoline Receptors; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C487767:imidazoline receptor 2; D019329:Idazoxan