title: Overexpressing neuroglobin improves functional recovery by inhibiting neuronal apoptosis after spinal cord injury.
abstract: The current study was performed to evaluate the mechanisms and therapeutic effects of overexpressing neuroglobin (Ngb) on spinal cord injury (SCI). Adeno-associated virus (AAV) was injected in the T12 section 7 days before SCI. Animals were randomly divided into four groups: a sham group, a vehicle group, an AAV-EGFP group and an AAV-Ngb group. Recovery of hind limb locomotor function was determined during the 3-week post operation period by the Basso, Beattie and Bresnahan locomotor rating scale. At 24 h after SCI and at the end of the study, the segments of spinal cord, centered with the lesion site were harvested for histopathological analysis. Immunofluorescence was performed using antibodies to recognize neuN in the lesion sections. At 24 h after SCI, the spinal cord tissue samples were removed to analyze tissue concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA). Apoptotic cells were assessed using a terminal deoxynucleotidyl transferase, dUTP nick end labeling (TUNEL) kit. The expression of bcl-2, bax, cytochrome c, and cleaved caspase-3, were determined by Western blot assay and immunostaining analysis. The results showed that animals overexpressing Ngb had significantly greater recovery of locomotor function, less neuronal loss and fewer apoptotic cells. In addition, overexpressing Ngb significantly increased bcl-2 expression and SOD level, decreased bax expression, attenuated the release of cytochrome c from mitochondria to the cytosol fraction, and reduced the activity of caspase-3 and MDA level after SCI. These findings suggest, that overexpressing Ngb can significantly improve the recovery of locomotor function. This neuroprotective effect may be associated with the inhibition of neural apoptosis via the mitochondrial pathway.
authors.affiliation: The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Lan
authors.affiliation: The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China. Electronic address: linjianhua0591@gmail.com.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Lin
authors.affiliation: The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Xuan-Wei
authors.initials: XW
authors.lastname: Chen
authors.affiliation: The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Chao-Yang
authors.initials: CY
authors.lastname: Wu
authors.affiliation: The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhong
authors.affiliation: The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, the 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Lin
authors.affiliation: Department of Orthopedics, the Affiliated People׳s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
authors.forename: Wei-Nan
authors.initials: WN
authors.lastname: Liu
authors.affiliation: The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Jin-Luan
authors.initials: JL
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D000229:Dependovirus; D015316:Genetic Therapy; D005822:Genetic Vectors; D005914:Globins / Q000235:genetics* / Q000378:metabolism*; D006614:Hindlimb; D008297:Male; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D000078787:Neuroglobin; D009474:Neurons / Q000502:physiology*; D010084:Oxidation-Reduction; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D013904:Thoracic Vertebrae
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins
keywords: Apoptosis; Mitochondrial pathway; Neuroglobin; Spinal cord injury