Detection of local and remote cellular damage caused by spinal cord and peripheral nerve injury using a heat shock signaling reporter system
Kazue Hashimoto-Torii,
Masanori Sasaki,
Yu-Wen Chang,
Hye Hwang,
Stephen G. Waxman,
Jeffery D. Kocsis,
Pasko Rakic,
Masaaki Torii
Affiliations
Kazue Hashimoto-Torii
Center for Neuroscience Research, Children’s Research Institute, Children’s National Medical Center, Washington, DC 20010, USA; Department of Pediatrics, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA; Department of Neurobiology and Kavli Institute for Neuroscience, School of Medicine, Yale University, New Haven, CT 06510, USA
Masanori Sasaki
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, 06510, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut, 06516, USA; Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, Japan
Yu-Wen Chang
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, 06510, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut, 06516, USA
Hye Hwang
Center for Neuroscience Research, Children’s Research Institute, Children’s National Medical Center, Washington, DC 20010, USA; Institute of Biomedical Sciences, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA
Stephen G. Waxman
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, 06510, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut, 06516, USA
Jeffery D. Kocsis
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, 06510, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut, 06516, USA
Pasko Rakic
Department of Neurobiology and Kavli Institute for Neuroscience, School of Medicine, Yale University, New Haven, CT 06510, USA
Masaaki Torii
Center for Neuroscience Research, Children’s Research Institute, Children’s National Medical Center, Washington, DC 20010, USA; Department of Pediatrics, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA; Department of Neurobiology and Kavli Institute for Neuroscience, School of Medicine, Yale University, New Haven, CT 06510, USA; Corresponding author at: 111 Michigan Avenue, N.W., M7631, Washington DC, 20010-2970, USA.
Spinal cord and peripheral nerve injury results in extensive damage to the locally injured cells as well as distant cells that are functionally connected to them. Both primary and secondary damage can cause a broad range of clinical abnormalities, including neuropathic pain and cognitive and memory dysfunction. However, the mechanisms underlying these abnormalities remain unclear, awaiting new methods to identify affected cells to enable examination of their molecular, cellular and physiological characteristics. Here, we report that both primary and secondary damage to cells in mouse models of spinal cord and peripheral nerve injury can be detected in vivo using a novel fluorescent reporter system based on the immediate stress response via activation of Heat Shock Factor 1. We also provide evidence for altered electrophysiological properties of reporter-positive secondarily-injured neurons. The comprehensive identification of injured, but surviving cells located both close and at distant locations from the injury site in vivo will provide a way to study their pathophysiology and possibly prevention of their further deterioration. Keywords: Heat shock signaling, Cellular damage, Spinal cord injury, Sciatic nerve injury, Reporter mouse
