Idazoxan attenuates spinal cord injury by enhanced astrocytic activation and reduced microglial activation in rat experimental autoimmune encephalomyelitis.

Abstract

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.

• Authors: Xin-Shi Wang, Yan-Yan Chen, Xiao-Feng Shang, Zhen-Guo Zhu, Guo-Qian Chen, Zhao Han, Bei Shao, Hui-Min Yang, Hui-Qin Xu, Jiang-Fan Chen, Rong-Yuan Zheng
• Journal: Brain research (Brain Res) Vol. 1253 Pg. 198-209 (Feb 09 2009) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 19083996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cytokines
• Imidazoline Receptors
• Neuroprotective Agents
• RNA, Messenger
• imidazoline receptor 2
• Idazoxan

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Astrocytes (drug effects, physiology)
• Cerebral Cortex (drug effects, metabolism)
• Cytokines (genetics, metabolism)
• Demyelinating Diseases (drug therapy)
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (drug therapy, physiopathology)
• Gene Expression Regulation
• Idazoxan (therapeutic use)
• Imidazoline Receptors (agonists, metabolism)
• Microglia (drug effects, physiology)
• Multiple Sclerosis (drug therapy, pathology, physiopathology)
• Neuroprotective Agents (therapeutic use)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Spinal Cord (pathology, physiopathology)