Cold protection allows local cryotherapy in a clinical-relevant model of traumatic optic neuropathy

Yikui Zhang, Mengyun Li, Bo Yu, Shengjian Lu, Lujie Zhang, Senmiao Zhu, Zhonghao Yu, Tian Xia, Haoliang Huang, Wenhao Jiang, Si Zhang, Lanfang Sun, Qian Ye, Jiaying Sun, Hui Zhu, Pingping Huang, Huifeng Hong, Shuaishuai Yu, Wenjie Li, Danni AiJingfan Fan, Wentao Li, Hong Song, Lei Xu, Xiwen Chen, Tongke Chen, Meng Zhou, Jingxing Ou, Wei Li, Jian Yang, Yang Hu, Wencan Wu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Therapeutic hypothermia (TH) is potentially an important therapy for central nervous system (CNS) trauma. However, its clinical application remains controversial, hampered by two major factors: 1) Many of the CNS injury sites, such as the optic nerve (ON), are deeply buried, preventing access for local TH. The alternative is to apply TH systemically, which significantly limits the applicable temperature range. 2) Even with possible access for “local refrigeration”, cold-induced cellular damage offsets the benefit of TH. Here we present a clinically translatable model of traumatic optic neuropathy (TON) by applying clinical trans-nasal endoscopic surgery to goats and non-human primates. This model faithfully recapitulates clinical features of TON such as the injury site (pre-chiasmatic ON), the spatiotemporal pattern of neural degeneration, and the accessibility of local treatments with large operating space. We also developed a computer program to simplify the endoscopic procedure and expand this model to other large animal species. Moreover, applying a cold-protective treatment, inspired by our previous hibernation research, enables us to deliver deep hypothermia (4°C) locally to mitigate inflammation and metabolic stress (indicated by the transcriptomic changes after injury) without cold-induced cellular damage, and confers prominent neuroprotection both structurally and functionally. Intriguingly, neither treatment alone was effective, demonstrating that in situ deep hypothermia combined with hibernation-mimicking cold protection constitutes a breakthrough for TH as a therapy for TON and other CNS traumas.

Original languageEnglish
Article numbere75070
JournaleLife
Volume11
DOIs
Publication statusPublished - Mar 2022

Fingerprint

Dive into the research topics of 'Cold protection allows local cryotherapy in a clinical-relevant model of traumatic optic neuropathy'. Together they form a unique fingerprint.

Cite this