Inflammation-induced GDNF improves locomotor function after spinal cord injury.
Activation of microglia/macrophages after injury occurs limitedly in the CNS, which finding may explain unsuccessful axonal regeneration. Therefore, the relationship between lipopolysaccharide (LPS)-induced inflammation and recovery of locomotor function of rats after spinal cord injury was examined. High-dose LPS improved locomotor function greater than low-dose LPS, being consistent with the expression of neurotrophic factor (GDNF) in microglia/macrophages. Experiments using GDNF gene mutant mice confirmed that the increase in the GDNF mRNA level, rather than the reduction in the mRNA level of inducible NO synthase, could be correlated with the restoration activity of locomotor function. These results suggest that a higher degree of inflammation leads to a higher degree of repair of CNS injuries through GDNF produced by activated microglia/macrophages.
Hashimoto
Manabu
M
Laboratory of Molecular Biology, Gifu Pharmaceutical University, 5-6-1, Mitahora-higashi, Gifu 502-8585, Japan.
Nitta
Atsumi
A
Fukumitsu
Hidefumi
H
Nomoto
Hiroshi
H
Shen
Liya
L
Furukawa
Shoei
S
D000818:Animals; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*
C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat