使用热休克信号报告系统检测脊髓和周围神经损伤引起的局部和远程细胞损伤。
Detection of local and remote cellular damage caused by spinal cord and peripheral nerve injury using a heat shock signaling reporter system.
作者信息
Hashimoto-Torii Kazue, Sasaki Masanori, Chang Yu-Wen, Hwang Hye, Waxman Stephen G, Kocsis Jeffery D, Rakic Pasko, Torii Masaaki
机构信息
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.
出版信息
IBRO Rep. 2018 Nov 6;5:91-98. doi: 10.1016/j.ibror.2018.11.003. eCollection 2018 Dec.
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 using a novel fluorescent reporter system based on the immediate stress response 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 will provide a way to study their pathophysiology and possibly prevention of their further deterioration.
脊髓和周围神经损伤会对局部受损细胞以及与它们功能相连的远处细胞造成广泛损害。原发性和继发性损伤均可导致一系列临床异常,包括神经性疼痛以及认知和记忆功能障碍。然而,这些异常背后的机制仍不清楚,有待新方法来识别受影响的细胞,以便研究它们的分子、细胞和生理特征。在此,我们报告,使用基于热休克因子1即时应激反应激活的新型荧光报告系统,可以检测脊髓和周围神经损伤小鼠模型中细胞的原发性和继发性损伤。我们还提供了报告基因阳性的继发性损伤神经元电生理特性改变的证据。对损伤部位附近和远处受损但存活的细胞进行全面鉴定,将为研究它们的病理生理学以及可能预防其进一步恶化提供一种方法。
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