Improved outcome of EAN, an animal model of GBS, through amelioration of peripheral and central inflammation by minocycline.
Experimental autoimmune neuritis (EAN) is a widely used animal model of the human acute inflammatory demyelinating polyradiculoneuropathy, which is the most common subtype of Guillain-Barré Syndrome. EAN is pathologically characterized by breakdown of the blood-nerve barrier, infiltration of reactive immune cells, local inflammation, demyelination in the peripheral nervous system and mechanical allodynia. Minocycline is known to have neuroprotective and anti-inflammatory effects. Furthermore, relieve of neuropathic pain following minocycline administration was observed in a variety of animal models. Here, we investigated the effects of minocycline on rat EAN. Suppressive treatment with minocycline (50 mg/kg body weight daily immediately after immunization) significantly attenuated the severity and duration of EAN. Macrophage and T-cell infiltration and demyelination in sciatic nerves of EAN rats treated with minocycline were significantly reduced compared to phosphate-buffered saline (PBS)-treated EAN rats. mRNA expressions of matrix metallopeptidase-9, inducible nitric oxide synthase and pro-inflammatory cytokines interleukin-1 beta and tumour necrosis factor-alpha in EAN sciatic nerves were greatly decreased by administration of minocycline as well. Furthermore, minocycline attenuated mechanical allodynia in EAN rats and greatly suppressed spinal microglial activation. All together, our data showed that minocycline could effectively suppress the peripheral and spinal inflammation (immune activation) to improve outcome in EAN rats, which suggests that minocycline may be considered as a potential candidate of pharmacological treatment for autoimmune-mediated neuropathies.
Zhang
Zhi-Yuan
ZY
Institute of Brain Research, University of Tuebingen, Germany.
Zhang
Zhiren
Z
Fauser
Uwe
U
Schluesener
Hermann J
HJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001835:Body Weight; D004195:Disease Models, Animal; D020275:Guillain-Barre Syndrome / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008911:Minocycline / Q000627:therapeutic use*; D009000:Monocytes / Q000378:metabolism; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy / Q000473:pathology; D010146:Pain / Q000378:metabolism; D051381:Rats; D012584:Sciatic Nerve / Q000201:enzymology / Q000473:pathology
D000900:Anti-Bacterial Agents; D020780:Matrix Metalloproteinase 9; D008911:Minocycline