Much of my research is part of the California Spinal Cord Injury Consortium, a group composed of researchers from UCSD, UCLA, UCSF, UC Irvine, UC Davis, Colorado State University, and Switzerland’s Ecole Polytechnique Federale de Lausanne. Drawing only the most promising candidate treatments from research in rodent models of SCI, we examine the neuroanatomical, electrophysiological, and functional efficacies of those treatments in animal models that better reproduce the conditions of human SCI. My main current focus is on the formation of long-distance neuronal relays using neural stem cells transplanted into SCI lesions. Additional studies are underway to evaluate the efficacy of enzymatic degradation of inhibitory chondroitin sulfate proteoglycans (CSPGs).
Successful grafting of GFP+ human NSCs to sites of non-human primate C7 lateral hemisection
(A,B) Grafts of human NSCs (H9-NSC and 566RSC, respectively) survive and integrate into lesion/host cord. (B) Tens of thousands of graft-derived axons, 6 mm caudal to the graft. D) Graft-derived axons surrounding host motor neurons (NeuN, red) 7 mm caudal to the graft. (E) Co-labeling with synaptophysin (Syn, red) suggests the formation of synapses on host motor neurons by graft-derived axons. (F) EM confirmation of synapse formation in host gray matter 7mm caudal to lesion. Graft-derived axon (Arrow) in close apposition to host dendrite, with synapse (Arrowheads). The asymmetric synaptic density and circular, dense-core vesicles suggest an excitatory synapse.
1. Rosenzweig ES, Brock JH, Lu P, Kumamaru H, Salegio EA, Kadoya K, Weber JL, Liang JJ, Moseanko R, Hawbecker S, Huie JR, Havton LA, Nout-Lomas YS, Ferguson AR, Beattie MS, Bresnahan JC, Tuszynski MH. Restorative effects of human neural stem cell grafts on the primate spinal cord. Nat Med. 2018 Feb 26; PMID: 29480894
2. Brock JH, Rosenzweig ES, Yang H, Tuszynski MH. Enhanced axonal transport: A novel form of “plasticity” after primate and rodent spinal cord injury. Exp Neurol. 2018 Mar;301(Pt A):59–69. PMID: 29277625
3. Salegio EA, Bresnahan JC, Sparrey CJ, Camisa W, Fischer J, Leasure J, Buckley J, Nout-Lomas YS, Rosenzweig ES, Moseanko R, Strand S, Hawbecker S, Lemoy M-J, Haefeli J, Ma X, Nielson JL, Edgerton VR, Ferguson AR, Tuszynski MH, Beattie MS. A Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates (Macaca mulatta). J Neurotrauma. 2016 Mar 1;33(5):439-459. PMCID: PMC4799702
4. Friedli L, Rosenzweig ES, Barraud Q, Schubert M, Dominici N, Awai L, Nielson JL, Musienko P, Nout-Lomas Y, Zhong H, Zdunowski S, Roy RR, Strand SC, van den Brand R, Havton LA, Beattie MS, Bresnahan JC, Bézard E, Bloch J, Edgerton VR, Ferguson AR, Curt A, Tuszynski MH, Courtine G. Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates. Sci Transl Med. 2015 Aug 26;7(302):302ra134.
5. Koffler J, Samara RF, Rosenzweig ES. Using templated agarose scaffolds to promote axon regeneration through sites of spinal cord injury. Methods Mol Biol. 2014;1162:157–65.
6. Nout YS, Rosenzweig ES, Brock JH, Strand SC, Moseanko R, Hawbecker S, Zdunowski S, Nielson JL, Roy RR, Courtine G, Ferguson AR, Edgerton VR, Beattie MS, Bresnahan JC, Tuszynski MH. Animal models of neurologic disorders: a nonhuman primate model of spinal cord injury. Neurotherapeutics. 2012 Apr;9(2):380–92.
7. Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, Brock J, Blesch A, Rosenzweig ES, Havton LA, Zheng B, Conner JM, Marsala M, Tuszynski MH. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell. 2012 Sep 14;150(6):1264–73.
8. Rosenzweig ES, Courtine G, Jindrich DL, Brock JH, Ferguson AR, Strand SC, Nout YS, Roy RR, Miller DM, Beattie MS, Havton LA, Bresnahan JC, Edgerton VR, Tuszynski MH. Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury. Nat Neurosci. 2010 Dec;13(12):1505–10.
9. Brock JH, Rosenzweig ES, Blesch A, Moseanko R, Havton LA, Edgerton VR, Tuszynski MH. Local and remote growth factor effects after primate spinal cord injury. J Neurosci. 2010 Jul 21;30(29):9728–37.
10. Rosenzweig ES, Brock JH, Culbertson MD, Lu P, Moseanko R, Edgerton VR, Havton LA, Tuszynski MH. Extensive spinal decussation and bilateral termination of cervical corticospinal projections in rhesus monkeys. J Comp Neurol. 2009 Mar 10;513(2):151–63.
11. Rosenzweig ES, Redish AD, McNaughton BL, Barnes CA. Hippocampal map realignment and spatial learning. Nat Neurosci. 2003 Jun;6(6):609–15.
12. Rosenzweig ES, Barnes CA. Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Prog Neurobiol. 2003 Feb;69(3):143–79.