Cargando…

Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest

Hypothermia enhances outcomes of patients after resuscitation after cardiac arrest (CA). However, the underlying mechanism is not fully understood. In this study, we investigated effects of hypothermic therapy on neuronal damage/death, microglial activation, and changes of endogenous antioxidants in...

Descripción completa

Detalles Bibliográficos
Autores principales: Ahn, Ji Hyeon, Lee, Tae-Kyeong, Kim, Bora, Lee, Jae-Chul, Tae, Hyun-Jin, Cho, Jeong Hwi, Park, Yoonsoo, Shin, Myoung Cheol, Ohk, Taek Geun, Park, Chan Woo, Cho, Jun Hwi, Hong, Seongkweon, Park, Joon Ha, Choi, Soo Young, Won, Moo-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023071/
https://www.ncbi.nlm.nih.gov/pubmed/31906329
http://dx.doi.org/10.3390/antiox9010038
_version_ 1783498164319289344
author Ahn, Ji Hyeon
Lee, Tae-Kyeong
Kim, Bora
Lee, Jae-Chul
Tae, Hyun-Jin
Cho, Jeong Hwi
Park, Yoonsoo
Shin, Myoung Cheol
Ohk, Taek Geun
Park, Chan Woo
Cho, Jun Hwi
Hong, Seongkweon
Park, Joon Ha
Choi, Soo Young
Won, Moo-Ho
author_facet Ahn, Ji Hyeon
Lee, Tae-Kyeong
Kim, Bora
Lee, Jae-Chul
Tae, Hyun-Jin
Cho, Jeong Hwi
Park, Yoonsoo
Shin, Myoung Cheol
Ohk, Taek Geun
Park, Chan Woo
Cho, Jun Hwi
Hong, Seongkweon
Park, Joon Ha
Choi, Soo Young
Won, Moo-Ho
author_sort Ahn, Ji Hyeon
collection PubMed
description Hypothermia enhances outcomes of patients after resuscitation after cardiac arrest (CA). However, the underlying mechanism is not fully understood. In this study, we investigated effects of hypothermic therapy on neuronal damage/death, microglial activation, and changes of endogenous antioxidants in the anterior horn in the lumbar spinal cord in a rat model of asphyxial CA (ACA). A total of 77 adult male Sprague–Dawley rats were randomized into five groups: normal, sham ACA plus (+) normothermia, ACA + normothermia, sham ACA + hypothermia, and ACA + hypothermia. ACA was induced for 5 min by injecting vecuronium bromide. Therapeutic hypothermia was applied after return of spontaneous circulation (ROSC) via rapid cooling with isopropyl alcohol wipes, which was maintained at 33 ± 0.5 °C for 4 h. Normothermia groups were maintained at 37 ± 0.2 °C for 4 h. Neuronal protection, microgliosis, oxidative stress, and changes of endogenous antioxidants were evaluated at 12 h, 1 day, and 2 days after ROSC following ACA. ACA resulted in neuronal damage from 12 h after ROSC and evoked obvious degeneration/loss of spinal neurons in the ventral horn at 1 day after ACA, showing motor deficit of the hind limb. In addition, ACA resulted in a gradual increase in microgliosis with time after ACA. Therapeutic hypothermia significantly reduced neuronal loss and attenuated hind limb dysfunction, showing that hypothermia significantly attenuated microgliosis. Furthermore, hypothermia significantly suppressed ACA-induced increases of superoxide anion production and 8-hydroxyguanine expression, and significantly increased superoxide dismutase 1 (SOD1), SOD2, catalase, and glutathione peroxidase. Taken together, hypothermic therapy was found to have a substantial impact on changes in ACA-induced microglia activation, oxidative stress factors, and antioxidant enzymes in the ventral horn of the lumbar spinal cord, which closely correlate with neuronal protection and neurological performance after ACA.
format Online
Article
Text
id pubmed-7023071
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70230712020-03-12 Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest Ahn, Ji Hyeon Lee, Tae-Kyeong Kim, Bora Lee, Jae-Chul Tae, Hyun-Jin Cho, Jeong Hwi Park, Yoonsoo Shin, Myoung Cheol Ohk, Taek Geun Park, Chan Woo Cho, Jun Hwi Hong, Seongkweon Park, Joon Ha Choi, Soo Young Won, Moo-Ho Antioxidants (Basel) Article Hypothermia enhances outcomes of patients after resuscitation after cardiac arrest (CA). However, the underlying mechanism is not fully understood. In this study, we investigated effects of hypothermic therapy on neuronal damage/death, microglial activation, and changes of endogenous antioxidants in the anterior horn in the lumbar spinal cord in a rat model of asphyxial CA (ACA). A total of 77 adult male Sprague–Dawley rats were randomized into five groups: normal, sham ACA plus (+) normothermia, ACA + normothermia, sham ACA + hypothermia, and ACA + hypothermia. ACA was induced for 5 min by injecting vecuronium bromide. Therapeutic hypothermia was applied after return of spontaneous circulation (ROSC) via rapid cooling with isopropyl alcohol wipes, which was maintained at 33 ± 0.5 °C for 4 h. Normothermia groups were maintained at 37 ± 0.2 °C for 4 h. Neuronal protection, microgliosis, oxidative stress, and changes of endogenous antioxidants were evaluated at 12 h, 1 day, and 2 days after ROSC following ACA. ACA resulted in neuronal damage from 12 h after ROSC and evoked obvious degeneration/loss of spinal neurons in the ventral horn at 1 day after ACA, showing motor deficit of the hind limb. In addition, ACA resulted in a gradual increase in microgliosis with time after ACA. Therapeutic hypothermia significantly reduced neuronal loss and attenuated hind limb dysfunction, showing that hypothermia significantly attenuated microgliosis. Furthermore, hypothermia significantly suppressed ACA-induced increases of superoxide anion production and 8-hydroxyguanine expression, and significantly increased superoxide dismutase 1 (SOD1), SOD2, catalase, and glutathione peroxidase. Taken together, hypothermic therapy was found to have a substantial impact on changes in ACA-induced microglia activation, oxidative stress factors, and antioxidant enzymes in the ventral horn of the lumbar spinal cord, which closely correlate with neuronal protection and neurological performance after ACA. MDPI 2020-01-01 /pmc/articles/PMC7023071/ /pubmed/31906329 http://dx.doi.org/10.3390/antiox9010038 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ahn, Ji Hyeon
Lee, Tae-Kyeong
Kim, Bora
Lee, Jae-Chul
Tae, Hyun-Jin
Cho, Jeong Hwi
Park, Yoonsoo
Shin, Myoung Cheol
Ohk, Taek Geun
Park, Chan Woo
Cho, Jun Hwi
Hong, Seongkweon
Park, Joon Ha
Choi, Soo Young
Won, Moo-Ho
Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest
title Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest
title_full Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest
title_fullStr Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest
title_full_unstemmed Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest
title_short Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest
title_sort therapeutic hypothermia improves hind limb motor outcome and attenuates oxidative stress and neuronal damage in the lumbar spinal cord following cardiac arrest
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023071/
https://www.ncbi.nlm.nih.gov/pubmed/31906329
http://dx.doi.org/10.3390/antiox9010038
work_keys_str_mv AT ahnjihyeon therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT leetaekyeong therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT kimbora therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT leejaechul therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT taehyunjin therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT chojeonghwi therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT parkyoonsoo therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT shinmyoungcheol therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT ohktaekgeun therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT parkchanwoo therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT chojunhwi therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT hongseongkweon therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT parkjoonha therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT choisooyoung therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest
AT wonmooho therapeutichypothermiaimproveshindlimbmotoroutcomeandattenuatesoxidativestressandneuronaldamageinthelumbarspinalcordfollowingcardiacarrest