Detection of local and remote cellular damage caused by spinal cord and peripheral nerve injury using a heat shock signaling reporter system

Highlights • The HSE-RFP reporter detects primarily- and secondarily-damaged neural cells in spinal cord injury. • The HSE-RFP reporter detects primarily- and secondarily-damaged neural cells in sciatic nerve injury. • Reporter-positive secondarily-injured neurons show altered physiological properties.
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.