title: Acid fibroblast growth factor and peripheral nerve grafts regulate Th2 cytokine expression, macrophage activation, polyamine synthesis, and neurotrophin expression in transected rat spinal cords.
abstract: Spinal cord injury elicits an inflammatory response that recruits macrophages to the injured spinal cord. Quantitative real-time PCR results have shown that a repair strategy combining peripheral nerve grafts with acidic fibroblast growth factor (aFGF) induced higher interleukin-4 (IL-4), IL-10, and IL-13 levels in the graft areas of rat spinal cords compared with transected spinal cords at 10 and 14 d. This led to higher arginase I-positive alternatively activated macrophage (M2 macrophage) responses. The gene expression of several enzymes involved in polyamine biosynthesis pathways was also upregulated in the graft areas of repaired spinal cords. The treatment induced a twofold upregulation of polyamine levels at 14 d, as confirmed by HPLC. Polyamines are important for the repair process, as demonstrated by the observation that treatment with inhibitors of arginase I and ornithine decarboxylase attenuates the functional recoveries of repaired rats. After 14 d, the treatment also induced the expression of neurotrophin nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as M2 macrophages within grafted nerves expressing BDNF. IL-4 was upregulated in the injury sites of transected rats that received aFGF alone compared with those that received nerve grafts alone at 10 d. Conversely, nerve graft treatment induced NGF and BDNF expression at 14 d. Macrophages expressing polyamines and BDNF may benefit axonal regeneration at 14 d. These results indicate that aFGF and nerve grafts regulate different macrophage responses, and M2 macrophages may play an important role in axonal regeneration after spinal cord injury in rats.
authors.affiliation: Neural Regeneration Laboratory and Center for Neural Regeneration, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Huai-Sheng
authors.initials: HS
authors.lastname: Kuo
authors.forename: May-Jywan
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Ming-Chao
authors.initials: MC
authors.lastname: Huang
authors.forename: Chuan-Wen
authors.initials: CW
authors.lastname: Chiu
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Tsai
authors.forename: Meng-Jen
authors.initials: MJ
authors.lastname: Lee
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Huang
authors.forename: Yi-Lo
authors.initials: YL
authors.lastname: Lin
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Kuo
authors.forename: Henrich
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015718:Fibrin Tissue Adhesive; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D007150:Immunohistochemistry; D007378:Interleukins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D010525:Peripheral Nerves / Q000637:transplantation*; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000628:therapy*; D058630:Spinal Cord Regeneration; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015718:Fibrin Tissue Adhesive; D007378:Interleukins; D009414:Nerve Growth Factors; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D016220:Fibroblast Growth Factor 1; D001119:Arginase; C542908:arginase I, rat