Xiao-Ming Xu, M.D., Ph.D.
Scientific Director, Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute
Professor and Mari Hulman George Chair of Neurological Surgery
Professor, Department of Anatomy and Cell Biology
Ph.D. The Ohio State University (1990)
Neuroprotection and Functional Regeneration following Spinal Cord Injury.
The goal of our laboratory is to study mechanisms underlying spinal cord injury (SCI) and develop novel repair strategies to improve anatomical reorganization and functional recovery in experimental models of SCI. Our long-term goal is to translate effective treatments from animal models to humans. To reach these goals, two lines of research are being conducted. First, we investigate novel molecules that may play a central role in mediating multiple injury insults such as inflammation, oxidative stress and glutamate toxicity during the course of secondary injury after an initial trauma. Our recent work suggests that phospholipase A2 (PLA2), a diverse family of phospholipid enzymes, may be such a molecule. We are currently studying mechanisms underlying PLA2-mediated secondary injury as well as testing agents that may block PLA2-mediated cytotoxicity and cell death and, therefore, enhance recovery of function in animal models of SCI. A second line of our research is to use cellular transplantation strategies to promote axonal regeneration through and beyond a lesion gap after SCI. SCI incurs disconnection of nerve fibers (called axons) and a successful repair strategy requires reconnection of these axons to their appropriate targets. Grafts of tissue engineered channels seeded with Schwann cells (SCs), a type of peripheral myelin-forming glial cells, can provide a necessary cellular alignment and environment to guide and support axonal growth in the bridge across the injury aftermath. Our lab has demonstrated that grafts of Schwann cell-seeded semi-permeable polymer channels created a permissive bridge between the stumps of the injured cord and promoted axonal regeneration and remyelination. Additionally, a complete therapy for functional regeneration after SCI should involve the use of combinatorial strategies including not only the cellular bridge but also other efficacious treatments such as boosting the intrinsic regenerative capacity of injured CNS neurons, overcoming the inhibitory environment associated with the glial scar and CNS myelin, providing growth-promoting pathways along the course of axonal regeneration, and enhancing synaptic reconnection between regenerating axons and their targets. Research along these lines is being conducted. It is our belief that the final repair of the injured spinal cord may be achieved by combining an early phase of neuroprotection and later phase of transplantation-mediated axonal regeneration.
Recent Publications (2009-2011; *: co-corresponding authors):
- Wang X, Smith GM, Xu X-M (2011) Preferential and bidirectional labeling of the rubrospinal tract with adenovirus-GFP for monitoring normal and injured axons. J Neurotrauma 28:635-647.
- Deng, L, Hu J, Liu N, Wang X, Smith GM, Wen X, Xu X-M (2011) GDNF modifies reactive astrogliosis allowing robust axonal regeneration through Schwann cell-seeded guidance channels after spinal cord injury Exp Neurol 229:238-250; with Cover Image
- Zhao Z, Liu N, Huang J, Lu P, Xu X-M (2011) Inhibition of cPLA2 activation by Ginkgo biloba extract protects spinal cord neurons from glutamate excitotoxicity and oxidative stress-induced cell death. J Neurochem 116:1057-1065 [NIHMS-260848; PMID-21182525; PMCID-PMC3059200]
- Brittain JM, Duarte DB, Wilson SM, Wang Y, Zhu W, Ballard C, Khanna M, Schmutzler BS, Xiong W, Brustovetsky T, Ripsch MS, Ashpole NM, Hingtgen CMd, Brustovetsky N, Hudmon A, Jin X, Vasko MR, Fehrenbacher JC, Liu N, Hurley JH, Xu X-M, White FA, and Khanna R (2011) Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca2+ channel complex. Nat Med 17:822-829.
- Yu P, Zhang Y-P, Shields LB, Zheng Y, Hu X, Hill R, Howard R, Gu Z, Burke DA, Whittemore SR, Xu X-M, Shields CB (2011) Inhibitor of DNA Binding 2 Promotes Sensory Axonal Growth after SCI. Exp Neurol 231:38-44.
- Shi, Y, Zhang, D, Huff TB, Wang X, Shi R, Xu X-M*, Cheng J-X* (2011) Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord. J Biomed Optics 16:106012-1˜106012-4.
- Byers JS, Huguenard AL, Kuruppu D, Liu NK, Xu X-M, Sengelaub DR (2012) Neuroprotective effects of testosterone on motoneuron and muscle morphology following spinal cord injury. J Comp Neurol 520:2683-2696. doi: 10.1002/cne.23066PMID: 22314886 [PMCID in process]
- Walker CL, Walker MJ, Liu N-K, Risberg EC, Gao X, Chen J, Xu X-M (2012) Systemic bisperoxovanadium activates Akt/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury. PLoS ONE 7-e30012 - doi 10.1371/journal.pone.0030012; PMCID: PMC3254642
- Liu Y-S, Feng Y-P, Xie J-X, Liu Y-S, Shen C-H, Niu F, Zou J, Tang S-F, Hao J, Xu J-X, Xiao L-P, Xu X-M*, Zhu H* (2012) A novel stretcher for immobilization and transportation of critically injured patients. PLoS ONE 7-e39544, doi:10.1371/journal.pone.0039544
- Hu J, Wang X, Deng L, Liu N, Gao X, Zhou F, Xu X-M (2012) Co-transplantation of oligodendrocyte progenitor cells and Schwann cells promotes functional recovery after spinal cord injury Cell Transplant (in press) DOI: 10.3727/096368912X661373
- Liu NK, Zhang Y-P, O’Connor J, Gianaris A, Oakes E, Lu Q-B, Verhovshek T, Walker C, Shields CB, Xu X-M (2013) A bilateral head injury that shows graded brain damage and behavior deficits in adult mice Brain Research (accepted) PMID:23276498
- Wu WJ, Wu W, Zou J, Shi F, Yang S, Liu Y, Lu P, Ma Z, Zhu H, Xu X-M (2013) Axonal and glial responses to a mid-thoracic spinal cord hemisection in the Macaca fascicularis monkey. J Neurotrauma (accepted) PMID:23421822
- Deng L, Deng P, Ruan Y, Xu ZC, Liu N, Wen X, Smith GM, Xu X-M (2013) A novel growth-promoting pathway formed by GDNF-overexpressing Schwann cells promotes propriospinal axonal regeneration, synapse formation, and partial recovery of function after spinal cord injury. J Neurosci 33:5655-5667
- Cai J, Zhang YP, Shields LBE, Zhang ZZ, Liu N, Xu X-M, Feng S-Q, Shields CB (2013) Correlation between electrophysiological properties, morphological maturation, and oligodendrocyte gene changes during postnatal motor tract development. Dev Neurobiol (Accepted)
- Kwon B, et al. (2013) Demonstrating efficacy in preclinical studies of cellular therapies for spinal cord injury – how much is enough? A functional group meeting on Oct. 18, 2012. J Neurotrauma (Accepted)
- Wang X, Hu J, She Y, Smith GM, Xu X-M (2013) Cortical PKC inhibition promotes axonal regeneration of the corticospinal tract and forelimb recovery after cervical dorsal spinal hemisection in adult rats Cerebral Cortex (Accepted)