title: Beneficial effects of thymosin β4 on spinal cord injury in the rat.
abstract: Thymosin β4 (Tβ4) has many physiological functions that are highly relevant to spinal cord injury (SCI), including neuronal survival, anti-inflammation, wound repair promotion, and angiogenesis. The present study investigated the therapeutic value of Tβ4 in SCI, with a focus on its neuroprotective, anti-inflammatory, and vasculoprotective properties. Tβ4 or a saline control was administered by intraperitoneal injection 30 min, 3 days, or 5 days after SCI with mild compression in rat. Locomotor recovery was tested with the Basso-Beattie-Bresnahan scale and a footprint analysis. All behavioral assessments were markedly improved with Tβ4 treatment. Histological examination at 7 days post injury showed that the numbers of surviving neurons and oligodendrocytes were significantly increased in Tβ4-treated animals compared to saline-treated controls. Levels of myelin basic protein, a marker of mature oligodendrocytes, in Tβ4-treated rats were 57.8% greater than those in saline-treated controls. The expression of ED1, a marker of activated microglia/macrophages, was reduced by 36.9% in the Tβ4-treated group compared to that of the saline-treated group. Tβ4 treatment after SCI was also associated with a significant decrease in pro-inflammatory cytokine gene expression and a significant increase in the mRNA levels of IL-10 compared to the control. Moreover, the size of lesion cavity delineated by astrocyte scar in the injured spinal cord was markedly reduced in Tβ4-treated animals compared to saline-treated controls. Given the known safety of Tβ4 in clinical trials and its beneficial effects on SCI recovery, the results of this study suggested that Tβ4 is a good candidate for SCI treatment in humans.
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Kuang
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China. Electronic address: jugong@fmmu.edu.cn.
authors.forename: Gong
authors.initials: G
authors.lastname: Ju
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China. Electronic address: jwangfm@fmmu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D004676:Myelin Basic Protein / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013947:Thymosin / Q000494:pharmacology*; D013997:Time Factors; D000099201:Thymosin beta(4)
chemical_list: D016207:Cytokines; D016753:Interleukin-10; D004676:Myelin Basic Protein; D018696:Neuroprotective Agents; D013947:Thymosin; D000099201:Thymosin beta(4); C436006:Mbp protein, rat
keywords: Neuroprotection; Rat; Spinal cord injury; Thymosin β4