Browsing by Author "Cheng, Xiaoxin"

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    Differential expression of sPLA2 following spinal cord injury and a functional role for sPLA2-IIA in mediating oligodendrocyte death
    (Wiley, 2009-11) Titsworth, W. Lee; Cheng, Xiaoxin; Ke, Yan; Deng, Lingxiao; Burckardt, Kenneth A.; Pendleton, Chris; Liu, Nai-Kui; Shao, Hui; Cao, Qi-Lin; Xu, Xiao-Ming; Department of Medicine, IU School of Medicine
    After the initial mechanical insult of spinal cord injury (SCI), secondary mediators propagate a massive loss of oligodendrocytes. We previously showed that following SCI both the total phospholipase activity and cytosolic PLA(2)-IV alpha protein expression increased. However, the expression of secreted isoforms of PLA(2) (sPLA(2)) and their possible roles in oligodendrocyte death following SCI remained unclear. Here we report that mRNAs extracted 15 min, 4 h, 1 day, or 1 month after cervical SCI show marked upregulation of sPLA(2)-IIA and IIE at 4 h after injury. In contrast, SCI induced down regulation of sPLA(2)-X, and no change in sPLA(2)-IB, IIC, V, and XIIA expression. At the lesion site, sPLA(2)-IIA and IIE expression were localized to oligodendrocytes. Recombinant human sPLA(2)-IIA (0.01, 0.1, or 2 microM) induced a dose-dependent cytotoxicity in differentiated adult oligodendrocyte precursor cells but not primary astrocytes or Schwann cells in vitro. Most importantly, pretreatment with S3319, a sPLA(2)-IIA inhibitor, before a 30 min H(2)O(2) injury (1 or 10 mM) significantly reduced oligodendrocyte cell death at 48 h. Similarly, pretreatment with S3319 before injury with IL-1 beta and TNFalpha prevented cell death and loss of oligodendrocyte processes at 72 h. Collectively, these findings suggest that sPLA(2)-IIA and IIE are increased following SCI, that increased sPLA(2)-IIA can be cytotoxic to oligodendrocytes, and that in vitro blockade of sPLA(2) can create sparing of oligodendrocytes in two distinct injury models. Therefore, sPLA(2)-IIA may be an important mediator of oligodendrocyte death and a novel target for therapeutic intervention following SCI.
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    Transplantation of Ciliary Neurotrophic Factor-Expressing Adult Oligodendrocyte Precursor Cells Promotes Remyelination and Functional Recovery after SpinalCord Injury
    (Society for Neuroscience, 2010-02-24) Cao, Qilin; He, Qian; Wang, Yaping; Cheng, Xiaoxin; Howard, Russell M.; Zhang, Yiping; DeVries, William H.; Shields, Christopher B.; Magnuson, David S. K.; Xu, Xiao-Ming; Kim, Dong H.; Whittemore, Scott R.; Neurological Surgery, School of Medicine
    Demyelination contributes to the dysfunction after traumatic spinal cord injury (SCI). We explored whether the combination of neurotrophic factors and transplantation of adult rat spinal cord oligodendrocyte precursor cells (OPCs) could enhance remyelination and functional recovery after SCI. Ciliary neurotrophic factor (CNTF) was the most effective neurotrophic factor to promote oligodendrocyte (OL) differentiation and survival of OPCs in vitro. OPCs were infected with retroviruses expressing enhanced green fluorescent protein (EGFP) or CNTF and transplanted into the contused adult thoracic spinal cord 9 d after injury. Seven weeks after transplantation, the grafted OPCs survived and integrated into the injured spinal cord. The survival of grafted CNTF-OPCs increased fourfold compared with EGFP-OPCs. The grafted OPCs differentiated into adenomatus polyposis coli (APC+) OLs, and CNTF significantly increased the percentage of APC+ OLs from grafted OPCs. Immunofluorescent and immunoelectron microscopic analyses showed that the grafted OPCs formed central myelin sheaths around the axons in the injured spinal cord. The number of OL-remyelinated axons in ventrolateral funiculus (VLF) or lateral funiculus (LF) at the injured epicenter was significantly increased in animals that received CNTF-OPC grafts compared with all other groups. Importantly, 75% of rats receiving CNTF-OPC grafts recovered transcranial magnetic motor-evoked potential and magnetic interenlargement reflex responses, indicating that conduction through the demyelinated axons in VLF or LF, respectively, was partially restored. More importantly, recovery of hindlimb locomotor function was significantly enhanced in animals receiving grafts of CNTF-OPCs. Thus, combined treatment with OPC grafts expressing CNTF can enhance remyelination and facilitate functional recovery after traumatic SCI.