Hepatocyte growth factor promotes endogenous repair and functional recovery after spinal cord injury.

Abstract

Many therapeutic interventions using neurotrophic factors or pharmacological agents have focused on secondary degeneration after spinal cord injury (SCI) to reduce damaged areas and promote axonal regeneration and functional recovery. Hepatocyte growth factor (HGF), which was identified as a potent mitogen for mature hepatocytes and a mediator of inflammatory responses to tissue injury, has recently been highlighted as a potent neurotrophic and angiogenic factor in the central nervous system (CNS). In the present study, we revealed that the extent of endogenous HGF up-regulation was less than that of c-Met, an HGF receptor, during the acute phase of SCI and administered exogenous HGF into injured spinal cord using a replication-incompetent herpes simplex virous-1 (HSV-1) vector to determine whether HGF exerts beneficial effects and promotes functional recovery after SCI. This treatment resulted in the significant promotion of neuron and oligodendrocyte survival, angiogenesis, axonal regrowth, and functional recovery after SCI. These results suggest that HGF gene delivery to the injured spinal cord exerts multiple beneficial effects and enhances endogenous repair after SCI. This is the first study to demonstrate the efficacy of HGF for SCI.

• Authors: Kazuya Kitamura, Akio Iwanami, Masaya Nakamura, Junichi Yamane, Kota Watanabe, Yoshinori Suzuki, Daisuke Miyazawa, Shinsuke Shibata, Hiroshi Funakoshi, Shinichi Miyatake, Robert S Coffin, Toshikazu Nakamura, Yoshiaki Toyama, Hideyuki Okano
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 85 Issue 11 Pg. 2332-42 (Aug 15 2007) ISSN: 0360-4012 [Print] United States
• PMID: 17549731 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2007 Wiley-Liss, Inc.

Chemical References

• Nerve Growth Factors
• RNA, Messenger
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-met

Topics

• Animals
• Blotting, Western
• Enzyme-Linked Immunosorbent Assay
• Female
• Gene Expression
• Genetic Therapy
• Genetic Vectors
• Hepatocyte Growth Factor (administration & dosage, metabolism)
• Immunohistochemistry
• Injections, Spinal
• Neovascularization, Physiologic
• Nerve Growth Factors (administration & dosage, metabolism)
• Nerve Regeneration (physiology)
• Neurons (metabolism)
• Oligodendroglia (metabolism)
• Proto-Oncogene Proteins c-met (metabolism)
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Spinal Cord Injuries (metabolism, therapy)
• Up-Regulation