title: Biphasic bisperoxovanadium administration and Schwann cell transplantation for repair after cervical contusive spinal cord injury.
abstract: Schwann cells (SCs) hold promise for spinal cord injury (SCI) repair; however, there are limitations for its use as a lone treatment. We showed that acute inhibition of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) by bisperoxovanadium (bpV) was neuroprotective and enhanced function following cervical hemicontusion SCI. We hypothesized that combining acute bpV therapy and delayed SC engraftment would further improve neuroprotection and recovery after cervical SCI. Adult female Sprague-Dawley (SD) rats were randomly sorted into 5 groups: sham, vehicle, bpV, SC transplantation, and bpV+SC transplantation. SCs were isolated from adult green fluorescent protein (GFP)-expressing SD rats (GFP-SCs). 200 μg/kg bpV(pic) was administered intraperitoneally (IP) twice daily for 7 days post-SCI in bpV-treated groups. GFP-SCs (1×10(6) in 5 μl medium) were transplanted into the lesion epicenter at the 8th day post-SCI. Forelimb function was tested for 10 weeks and histology was assessed. bpV alone significantly reduced lesion (by 40%, p<0.05) and cavitation (by 65%, p<0.05) and improved functional recovery (p<0.05) compared to injury alone. The combination promoted similar neuroprotection (p<0.01 vs. injury); however, GFP-SCs alone did not. Both SC-transplanted groups exhibited remarkable long-term SC survival, SMI-31(+) axon ingrowth and RECA-1(+) vasculature presence in the SC graft; however, bpV+SCs promoted an 89% greater axon-to-lesion ratio than SCs only. We concluded that bpV likely contributed largely to the neuroprotective and functional benefits while SCs facilitated considerable host-tissue interaction and modification. The combination of the two shows promise as an attractive strategy to enhance recovery after SCI.
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Chandler L
authors.initials: CL
authors.lastname: Walker
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Carli
authors.initials: C
authors.lastname: Bullis
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Nai-Kui
authors.initials: NK
authors.lastname: Liu
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Fry
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Deng
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: xu26@iupui.edu.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005552:Forelimb / Q000503:physiopathology; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000628:therapy; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012583:Schwann Cells / Q000502:physiology* / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000601:surgery*; D013997:Time Factors; D017968:Vanadium Compounds / Q000627:therapeutic use*
chemical_list: D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; C568780:Esam protein, rat; D005904:Glial Fibrillary Acidic Protein; D017968:Vanadium Compounds; C472777:bisperoxovanadium; D049452:Green Fluorescent Proteins
keywords: Neuroprotection; PTEN; Schwann cell transplantation; Spinal cord injury; bpV