PEG mediated nervous system repair
Axonal damage is the key pathological change leading to nerve degeneration and functional loss. In particular, axonal membrane disruption resulting from mechanical insult plays pivotal roles in causing axonal degeneration and subsequent cell death. We have shown that polyethylene glycol (PEG, MW: 2,000), a hydrophilic polymer, can reconnect severed axons, repair membrane disruptions in crushed axons, and restore axonal conduction in isolated spinal cord strips. We have also shown that PEG can restore functions of injured mitochondria in both in vivo and in vitro conditions. PEG also improves behavioral outcome in rodent spinal cord and brain injury models. Ongoing investigation is aiming at revealing the mechanisms by which PEG repairs axonal membrane and mitochondria at the subcellular level. Such study is important in developing new therapeutic strategies for neural trauma based on the mechanism(s) of PEG-effect in both axolemmal and mitochondria.
Selected publications related to the topic:
Shi, R. and Borgens, R.B. Acute repair of crushed guinea pig spinal cord by polyethylene glycol. J. Neurophysiol. 81:2406-2414, 1999.
Shi, R., Blight, A.R. and Borgens, R.B. Functional reconnection of severed mammalian spinal cord axons by a molecular surfactant. J. Neurotrauma 16:727-738, 1999.
Borgens, R.B. and Shi, R. Immediate recovery from spinal cord injury through molecular repair of nerve membranes with polyethylene glycol. FASEB J. 14: 27-35, 2000.
Shi, R. and Borgens, R.B. Anatomical repair of nerve membranes in crushed mammalian spinal cord with polyethylene glycol. J. Neurocytol. 29:633-643 2000.
Borgens R.B., Shi, R. and Bohnert, D.M. Behavioral recovery from spinal cord injury following delayed application of polyethylene glycol. J. Exp. Bio. 205: 1-12, 2002.
Donaldson, J., Shi, R. and Borgens, R.B. Polyethylene glycol rapidly restores physiological functions in damaged sciatic nerves of the guinea pig. Neurosurgery 50: 147-157, 2002.
Luo, J., Borgens, R.B. and Shi, R. Polyethylene glycol immediately repairs neuronal membranes and inhibits free radical production after acute spinal cord injury. J. Neurochem. 83: 421-480, 2002.
Luo, J., Borgens, R.B. and Shi, R. Polyethylene glycol improves function and reduces oxidative stress in synaptosomes following spinal cord injury. J. Neurotrauma 21:994-1007, 2004.
Luo, J., and Shi, R. Polyethylene glycol inhibits apoptotic cell death following traumatic spinal cord injury. Brain Research. 1155: 10-16. 2007.
Liu-Snyder, P., Logan, M.P., Shi, R., Smith D.T., and Borgens, R. B. Neuroprotection from secondary injury by polyethylene glycol requires its intracellular presence. Journal Experimental Biology. 282: 13073-86. 2007
Cho, Y., Shi, R., Borgens, R and Ivanisevic, A. Repairing the damaged spinal cord and brain with nanomedicine. Small. 4: 1676-1681.2008.
Chen, H., Quick, E., Leung, G., Hamann, K., Fu, Y., Cheng, J and Shi, R. Polyethylene Glycol protects injured neuronal mitochondria. Pathobiology . 76: 117-128, 2009.
Shi, Y, Kim, S., Huff, T., Borgens, R., Park, K., Shi, R., and Cheng, J. Effective repair of traumatically injured spinal cord by block copolymer micelles: A pilot study. Nature Nanotechnology. 5: 80-87, 2010
Nehrt, A, Hammann, K., Ouyang, H., and Shi, R. Polyethylene glycol enhances axolemmal resealing following transetion in cultured cells and in ex vivo spinal cord. Journal of Neurotrauma. 27: 151-161, 2010.