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Article: Postcooling But Not Precooling Benefits Motor Recovery by Suppressing Cell Death After Surgical Spinal Cord Injury in Rats

TitlePostcooling But Not Precooling Benefits Motor Recovery by Suppressing Cell Death After Surgical Spinal Cord Injury in Rats
Authors
KeywordsApoptosis
Neuroprotection
Pyroptosis
Regional hypothermia
Surgical spinal cord injury
Issue Date2022
Citation
World Neurosurgery, 2022, v. 159, p. e356-e364 How to Cite?
AbstractBackground: Surgical 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. Methods: An 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. Results: RH 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. Conclusions: Priming 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.
Persistent Identifierhttp://hdl.handle.net/10722/330752
ISSN
2023 Impact Factor: 1.9
2023 SCImago Journal Rankings: 0.654
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, Ning-
dc.contributor.authorChau, Charlene Y.C.-
dc.contributor.authorLiu, Jiaxin-
dc.contributor.authorYao, Min-
dc.contributor.authorKiang, Karrie M.Y.-
dc.contributor.authorZhu, Zhiyuan-
dc.contributor.authorZhang, Pingde-
dc.contributor.authorCheng, Huilin-
dc.contributor.authorLeung, Gilberto K.K.-
dc.date.accessioned2023-09-05T12:13:53Z-
dc.date.available2023-09-05T12:13:53Z-
dc.date.issued2022-
dc.identifier.citationWorld Neurosurgery, 2022, v. 159, p. e356-e364-
dc.identifier.issn1878-8750-
dc.identifier.urihttp://hdl.handle.net/10722/330752-
dc.description.abstractBackground: Surgical 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. Methods: An 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. Results: RH 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. Conclusions: Priming 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.-
dc.languageeng-
dc.relation.ispartofWorld Neurosurgery-
dc.subjectApoptosis-
dc.subjectNeuroprotection-
dc.subjectPyroptosis-
dc.subjectRegional hypothermia-
dc.subjectSurgical spinal cord injury-
dc.titlePostcooling But Not Precooling Benefits Motor Recovery by Suppressing Cell Death After Surgical Spinal Cord Injury in Rats-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.wneu.2021.12.049-
dc.identifier.pmid34942389-
dc.identifier.scopuseid_2-s2.0-85122263297-
dc.identifier.hkuros334067-
dc.identifier.volume159-
dc.identifier.spagee356-
dc.identifier.epagee364-
dc.identifier.eissn1878-8769-
dc.identifier.isiWOS:000819845600018-

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