• Ning Li, Charlene Y C Chau, Jiaxin Liu, Min Yao, Karrie M Y Kiang, Zhiyuan Zhu, Pingde Zhang, Huilin Cheng, and LeungGilberto K KGKKDepartment of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR. Electronic address: gilberto@hku.hk..
• Department of Neurosurgery, Zhongda Hospital, Southeast University, Nanjing, China; Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.
• World Neurosurg. 2022 Mar 1; 159: e356e364e356-e364.

BackgroundSurgical spinal cord injury (SSCI) is often inevitable in patients with intramedullary lesions. Although regional hypothermia (RH) has been demonstrated neuroprotective, the value of priming RH in SSCI has never been studied. Herein, the authors investigated the impact of pre- and post-RH on neurologic recovery in a clinically relevant model.MethodsAn SSCI model was established at T10. RH was conducted by focal 4oC saline perfusion; room temperature (RT) saline was used as controls. Animals were randomized into 6 groups: SHAM-RT/RH, Pre-RT/RH, and Post-RT/RH. Motor and sensory functions were evaluated using the Basso, Beattie, and Bresnahan rating scale and Plantar test 2 weeks after surgery. TUNEL assay and Fluoro-Jade C staining were conducted to examine the cell death, and the alterations of apoptotic markers including total and cleaved casepase 3, Bcl-2, and Bax, as well as the pyroptotic proteins including NLRP3, ASC, and caspase 1, were determined.ResultsRH perfusion successfully created an intramedullary hypothermia approximately at 24oC, while RT controls remained above 30oC. Animals receiving postinjury RH had the least cell death and the best motor performance, while pre-RH showed the most dead cells and worst hind limb movements. Immunoblotting depicted that post-RH suppressed both apoptotic and pyroptotic death as the cleaved/total caspase 3, Bcl-2/Bax ratio, and NLRP3/ASC/caspase 1 signaling were inhibited. Priming cooling, on the contrary, elevated pyroptosis and did not affect apoptosis significantly.ConclusionsPriming RH before surgical incision could not be supported as it caused excessive cell death. In contrast, instant introduction of RH is beneficial in rescuing neurologic function.Copyright © 2021 Elsevier Inc. All rights reserved.

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