Armin Blesch, Ph.D.
Professor of Neurological Surgery
M.S., University of Würzburg, Germany (1992)
Ph.D., University of Würzburg, Germany (1995)
Postdoctoral Training, University of California, San Diego (1995-1998)
Regeneration and Plasticity in the Injured Spinal Cord.
The overall goal of our research is to identify mechanisms that influence neuronal plasticity and regeneration in the injured mammalian nervous system to identify new targets and techniques for therapeutic intervention. Current studies investigate the potential role of neural stem cells, biomaterials and neuronal activity as a means for spinal cord regeneration, and the structural changes underlying the development of pain after spinal cord injury. The latter together with evaluation of bladder dysfunction and autonomic responses after injury represent clinically relevant outcome measures complementing a strong focus on cellular and molecular mechanisms. Ongoing studies include:
Neural stem cell transplantation: Advancements in the generation and differentiation of neural stem cells from adult sources by cellular reprogramming has opened fascinating new opportunities to investigate questions that were impossible to address just a few years ago. In particular, we are interested in means to manipulate the differentiation of neural stem cells into phenotypes appropriate for neuronal relays in the spinal cord and means to augment the integration of transplanted cells in the spinal cord circuitry. To address these questions, we take advantage of new methods to manipulate the activity of grafted cells and to introduce specific mutations into stem cells. The main hypothesis underlying these experiments is that new transplanted neurons will only be able to have a functional influence if they are appropriately integrated into the injured circuitry.
Biomaterials: Regeneration of axons for long distances and across a lesion site remains a major challenge especially in lesions of the human spinal cord. Achieving linear axonal growth across a lesion in the spinal cord is likely necessary for axons to reach the distal host spinal cord. In collaboration with Dr. Müller (Univ. of Regensburg, Germany) and Dr. Weidner, Heidelberg University Hospital, we are using anisotropic alginate capillary gels to physically guide axons across the lesion site. Modification of channel diameters, cellular seeding into the channels and surface modification with peptides are variables that we continue to investigate.
Pain in spinal cord injury: In mouse models of spinal cord injury, we aim to address mechanisms of neuropathic pain and activity-dependent approaches to modulate spinal cord plasticity underlying pain. Mouse models will allow us to silence or ablate specific subpopulations of sensory neurons to determine their influence on pain responses.
Electrical stimulation: There is considerable evidence that electrical stimulation can enhance axonal regeneration in the PNS. In the CNS, some studies suggest that sprouting of spared fibers can be enhanced by electrical stimulation. We aim to determine whether electrical stimulation can also enhance regeneration in the CNS and to define the mechanisms underlying these responses. Studies conducted in collaboration with Karim Fouad, Univ. of Alberta focus on corticospinal and dorsal column sensory axons.
I. Peer-reviewed Original Publications:
Nees TA, Tappe-Theodor A, Sliwinski C, Motsch M, Rupp R, Kuner R, Weidner N, Blesch A (2015). Early-onset treadmill training reduces mechanical allodynia and modulates CGRP fiber density in lamina III/IV in a mouse model of spinal cord contusion injury. Pain: in press.
Günther MI, Weidner N, Müller R, Blesch A (2015). Cell-seeded alginate hydrogel scaffolds promote directed linear axonal regeneration in the injured rat spinal cord. Acta Biomat: 27:140-50. doi: 10.1016/j.actbio.2015.09.001. PMID: 26348141
Günther MI, Günther M, Schneiders M, Rupp R, Blesch A (2015). AngleJ, a new tool for the automated measurement of neurite growth orientation in tissue sections. J Neurosci Methods: 251:143-150. doi: 10.1016/j.jneumeth.2015.05.021. PMID: 26051555
Ruschel J, Hellal F, Flynn KC Sebastian Dupraz S, Bates M, Sliwinski C, Blesch A, Weidner N, Bunge MB, Bixby JL, Frank Bradke F (2015). Systemic administration of Epothilone B promotes axon regeneration and functional recovery after spinal cord injury. Science: 48(6232):347-352. doi: 10.1126/science.aaa2958. PMID: 25765066.
Sandner B, Ciatipis M, Motsch M, Soljanik I, Weidner N, Blesch A (2015). Limited functional effects of subacute syngeneic bone marrow stromal cell transplantation after contusion spinal cord injury. Cell Transplant: [Epub ahead of print]. PMID: 25812176
Fouad K, Bennett D, Vavrek R, Blesch A (2013). Long-term viral brain-derived neurotrophic factor delivery promotes spasticity in rats with a cervical spinal cord hemisection. Front Neurol: 4:187. doi: 10.3389/fneur.2013.00187.
Hou S, Tom V, Graham L, Lu P, Blesch A (2013). Partial restoration of cardiovascular function by embryonic neural stem cell grafts after complete spinal cord transection. J Neurosci: 33:17138-17149.
Hou S, Nicholson L, van Niekerk E, Motsch M, Blesch A (2012). Dependence of regenerated sensory axons on continuous neurotrophin-3 delivery. J Neurosci: 32:13206 –13220.
Blesch A, Lu P, Tsukada S, Taylor L, Roet K, Coppola G, Geschwind D, Tuszynski MH (2012). Conditioning lesions before or after spinal cord injury recruit broad genetic mechanisms that sustain axonal regeneration: superiority to cAMP-mediated effects. Exp Neurol: 235:162-173.
Kadoya K, Tsukada S, Lu P, Coppola G, Geschwind D, Filbin M, Blesch A, Tuszynski MH (2009). Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury. Neuron: 64(2):165-172.
Taylor-Alto L, Havton LA, Conner JM, Ma L, Blesch A*, Tuszynski MH* (2009) Chemotrophic guidance facilitates axonal regeneration into brainstem targets and synapse formation after spinal cord injury. Nat Neurosci: 12:1106-1113 (*corresponding authors)
Alfa R, Tuszynski MH, Blesch A (2009). A novel inducible tyrosine kinase receptor for regulated signal transduction and neurite outgrowth. J Neurosci Res: 87:2624-2631.
Nagahara A, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shakked, GM, Wang L, Blesch A, Kim A, Conner JM, Rockenstein E, Chao MV, Koo E, Geschwind D, Masliah E, Chiba AA, Tuszynski MH (2009). Neuroprotective effects of BDNF in rodent and primate models of Alzheimer’s disease. Nat Med: 15(3):331-337.
Hollis ER, Jamshidi P, Löw K, Blesch A, Tuszynski MH (2009). Induction of corticospinal regeneration by lentiviral trkB-induced erk activation. Proc Natl Acad Sci, U S A: 106:7215-7220.
Blesch A, Tuszynski MH (2007). Transient growth factor delivery retains regenerated axons after spinal cord injury. J Neurosci: 27:10535-10545.
Taylor L, Jones L, Tuszynski MH, Blesch A (2006). NT-3 gradients established by lentiviral gene transfer promote short-distance axonal bridging into and beyond cellular grafts in the injured spinal cord. J Neurosci: 26: 9713-9721.
Blesch A, Conner J, Pfeiffer A, Gasmi M, Britton W, Alfa R, Verma I, Tuszynski MH (2005). Regulated lentiviral NGF gene transfer controls rescue of medial septal cholinergic neurons. Mol Ther: 11: 916-925.
Tuszynski MH, Thal L, Pay M, Salmon D, U H-S, Bakay R, Blesch A, Vahlsing L, Ho G, Tong G, Potkin S, Fallon J, Mufson E, Kordower J, Gall C, Conner J (2005). A phase I clinical trial of nerve growth factor gene therapy for Alzheimer’s disease. Nature Med: 11:551-555.
Vroemen M, Weidner N and Blesch A (2005). Loss of gene expression in lentivirus- and retrovirus- transduced neural progenitor cells is correlated to migration and differentiation in the adult spinal cord: Exp Neurol: 195:127-139.
Blesch A, Yang H, Weidner N, Hoang A, Otero D (2004). Axonal responses to cellularly delivered NT-4/5 after spinal cord injury. Mol Cell Neurosci: 27: 190-201.
II. Reviews und Book Chapters:
Franz S, Weidner N, Blesch A (2012). Gene therapy approaches to enhancing plasticity and regeneration after spinal cord injury. Exp Neurol: 235:62-69
McCall J, Weidner N, Blesch A (2012). Neurotrophic factors in combinatorial approaches for spinal cord regeneration. Cell Tissue Res: 349:27-37.
Blesch A, Tuszynski MH (2008) Neurotrophic Factors in Alzheimer’s disease. In: Tuszynski MH, Kordower JH (eds.). CNS Regeneration: Basic Science and Clinical Advamces (2nd ed). Academic Press, Oxford, pp 201-223.
Blesch A, Tuszynski MH (2008). Neural repair: axonal regeneration and functional recovery: Neurotrophic factor therapy: NGF, BDNF and NT3. In: Larry R. Squire (Editor-in-Chief) . Encyclopedia of Neuroscience: Vol. 6, pp.1093-1100, Academic Press, Oxford.
Blesch A, Tuszynski MH (2008). Spinal cord injury: plasticity, regeneration and the challenge of translational drug development. Trends Neurosci: 32(1):41-47.
Alfa RW and Blesch A (2006). Murine and HIV-based retroviral vectors for in vitro and in vivo gene transfer. In: Wang Q (ed.): Methods in Molecular Medicine: Cardiovascular Disease: Methods and Protocols: 129:241-254.
Blesch A (2006). Neurotrophin gene therapy for Alzheimer’s disease. Future Neurol: 1: 179-187.
Blesch A (2006). Neurotrophic factors in neurodegeneration. Brain Pathol: 16:295-303.
Tuszynski MH, Blesch A (2004). Nerve growth factor: from animal models of cholinergic neuronal degeneration to gene therapy in Alzheimer’s disease. Prog Brain Res: 146:441-449.
Blesch A (2004). MLV based retroviral and lentiviral vectors for in vitro and in vivo gene transfer. Methods: 33:164-172.
Blesch A, Tuszynski MH (2004). Nucleus hears axon’s pain. Nat Med: 10: 236-237.