Isoflurane postconditioning reduces ischemia-induced nuclear factor-κB activation and interleukin 1β production to provide neuroprotection in rats and mice
Hong Li, Jinbo Yin, Liaoliao Li, Jiao Deng, Chenzhuo Feng, Zhiyi Zuo, Hong Li, Jinbo Yin, Liaoliao Li, Jiao Deng, Chenzhuo Feng, Zhiyi Zuo
Abstract
Application of isoflurane, a volatile anesthetic, after brain ischemia can reduce ischemic brain injury in rodents (isoflurane postconditioning). This study is designed to determine whether isoflurane postconditioning improves long-term neurological outcome after focal brain ischemia and whether this protection is mediated by attenuating neuroinflammation. Adult male Sprague-Dawley rats were subjected to a 90-min middle cerebral arterial occlusion (MCAO). Isoflurane postconditioning was performed by exposing rats to 2% isoflurane for 60min immediately after the MCAO. Isoflurane postconditioning reduced brain infarct volumes, apoptotic cells in the ischemic penumbral brain tissues and neurological deficits of rats at 4weeks after the MCAO. Isoflurane postconditioning reduced brain ischemia/reperfusion-induced nuclear transcription factor (NF)-κB (NF-κB) activation as well as interleukin 1β (IL-1β) and interleukin-6 production in the ischemic penumbral brain tissues at 24h after the MCAO. IL-1β deficient mice had smaller brain infarct volumes and better neurological functions than wild-type mice at 24h after a 90-min focal brain ischemia. Isoflurane posttreatment failed to induce neuroprotection in the IL-1β deficient mice. Our results suggest that isoflurane postconditioning improved long-term neurological outcome after transient focal brain ischemia. This protection may be mediated by inhibiting NF-κB activation and the production of the proinflammatory cytokine IL-1β.
Conflict of interest statement
Conflict of interest: The authors declare no other financial supports for this study, except for those grants stated on the title page from funding agencies for nonprofit. The authors also declare no conflict of interest in the content of this study.
Copyright © 2013 Elsevier Inc. All rights reserved.
Figures
![Fig. 1. Diagrammatic presentation of the experimental…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3628970/bin/nihms440407f1.jpg)
![Fig. 2. Isoflurane postconditioning improved histological and…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3628970/bin/nihms440407f2.jpg)
![Fig. 3. Isoflurane postconditioning reduced dying cells…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3628970/bin/nihms440407f3.jpg)
Fig. 4. Attenuation of ischemia-reperfusion-induced interleukin (IL)-1β…
Fig. 4. Attenuation of ischemia-reperfusion-induced interleukin (IL)-1β (panel A), IL-6 (panel B) and IL-10 (panel…
Fig. 5. Isoflurane postconditioning reduced translocation of…
Fig. 5. Isoflurane postconditioning reduced translocation of p65 to nuclei after the middle cerebral arterial…
Fig. 6. Isoflurane posttreatment reduced lipopolysaccharid (LPS)-induced…
Fig. 6. Isoflurane posttreatment reduced lipopolysaccharid (LPS)-induced interleukin (IL)-1β increase in mice
The frontal cerebral…
Fig. 7. Interleukin (IL)-1β deficient mice had…
Fig. 7. Interleukin (IL)-1β deficient mice had better histological and neurological function outcome than wild-type…
Fig. 8. Isoflurane post-treatment failed to induce…
Fig. 8. Isoflurane post-treatment failed to induce neuroprotection in interleukin (IL)-1β deficient mice after middle…
- Isoflurane preconditioning improves short-term and long-term neurological outcome after focal brain ischemia in adult rats.Li L, Zuo Z. Li L, et al. Neuroscience. 2009 Dec 1;164(2):497-506. doi: 10.1016/j.neuroscience.2009.08.011. Epub 2009 Aug 11. Neuroscience. 2009. PMID: 19679170 Free PMC article.
- Inhibition of brain ischemia-caused notch activation in microglia may contribute to isoflurane postconditioning-induced neuroprotection in male rats.Yin J, Li H, Feng C, Zuo Z. Yin J, et al. CNS Neurol Disord Drug Targets. 2014;13(4):718-32. doi: 10.2174/1871527313666140618110837. CNS Neurol Disord Drug Targets. 2014. PMID: 24938773
- Isoflurane postconditioning induces neuroprotection via Akt activation and attenuation of increased mitochondrial membrane permeability.Li L, Zuo Z. Li L, et al. Neuroscience. 2011 Dec 29;199:44-50. doi: 10.1016/j.neuroscience.2011.10.022. Epub 2011 Oct 20. Neuroscience. 2011. PMID: 22040798 Free PMC article.
- Wnt/β-catenin signaling pathway contributes to isoflurane postconditioning against cerebral ischemia-reperfusion injury and is possibly related to the transforming growth factorβ1/Smad3 signaling pathway.Zhang G, Ge M, Han Z, Wang S, Yin J, Peng L, Xu F, Zhang Q, Dai Z, Xie L, Li Y, Si J, Ma K. Zhang G, et al. Biomed Pharmacother. 2019 Feb;110:420-430. doi: 10.1016/j.biopha.2018.11.143. Epub 2018 Dec 5. Biomed Pharmacother. 2019. PMID: 30530044
- [The effects of preconditioning and postconditioning with isoflurane on focal cerebral ischemi/reperfusion injury in rats].Li G, Jia J, Fu J, Wang H, Ji K, Zang B. Li G, et al. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014 Jun;26(6):431-5. doi: 10.3760/cma.j.issn.2095-4352.2014.06.013. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014. PMID: 24912644 Chinese.
- Novel derivatives of eugenol as potent anti-inflammatory agents via PPARγ agonism: rational design, synthesis, analysis, PPARγ protein binding assay and computational studies.Anjum NF, Shanmugarajan D, Shivaraju VK, Faizan S, Naishima NL, Prashantha Kumar BR, Javid S, Purohit MN. Anjum NF, et al. RSC Adv. 2022 Jun 7;12(26):16966-16978. doi: 10.1039/d2ra02116a. eCollection 2022 Jun 1. RSC Adv. 2022. PMID: 35754905 Free PMC article.
- Activation of the Lateral Habenula-Ventral Tegmental Area Neural Circuit Contributes to Postoperative Cognitive Dysfunction in Mice.Xin J, Shan W, Li J, Yu H, Zuo Z. Xin J, et al. Adv Sci (Weinh). 2022 Aug;9(22):e2202228. doi: 10.1002/advs.202202228. Epub 2022 May 26. Adv Sci (Weinh). 2022. PMID: 35616407 Free PMC article.
- Critical role of FPR1 in splenocyte migration into brain to worsen inflammation and ischemic brain injury in mice.Li J, Chordia MD, Zhang Y, Zong H, Pan D, Zuo Z. Li J, et al. Theranostics. 2022 Mar 21;12(7):3024-3044. doi: 10.7150/thno.57218. eCollection 2022. Theranostics. 2022. PMID: 35547761 Free PMC article.
- Dynamics of isoflurane-induced vasodilation and blood flow of cerebral vasculature revealed by multi-exposure speckle imaging.Sullender CT, Richards LM, He F, Luan L, Dunn AK. Sullender CT, et al. J Neurosci Methods. 2022 Jan 15;366:109434. doi: 10.1016/j.jneumeth.2021.109434. Epub 2021 Dec 1. J Neurosci Methods. 2022. PMID: 34863840 Free PMC article.
- Translational challenges of remote ischemic conditioning in ischemic stroke - a systematic review.Hansen LF, Nielsen NSK, Christoffersen LC, Kruuse C. Hansen LF, et al. Ann Clin Transl Neurol. 2021 Aug;8(8):1720-1729. doi: 10.1002/acn3.51405. Epub 2021 Jun 16. Ann Clin Transl Neurol. 2021. PMID: 34133841 Free PMC article.
- Research Support, N.I.H., Extramural
- Animals
- Blotting, Western
- Brain Ischemia / metabolism*
- Brain Ischemia / pathology
- Enzyme-Linked Immunosorbent Assay
- In Situ Nick-End Labeling
- Interleukin-1beta / biosynthesis*
- Ischemic Postconditioning / methods*
- Isoflurane / pharmacology*
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- NF-kappa B / metabolism*
- Neuroprotective Agents / pharmacology*
- Rats
- Rats, Sprague-Dawley
- Recovery of Function / drug effects
- Interleukin-1beta
- NF-kappa B
- Neuroprotective Agents
- Isoflurane
- Full Text Sources
- Other Literature Sources
- Medical
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Fig. 4. Attenuation of ischemia-reperfusion-induced interleukin (IL)-1β…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3628970/bin/nihms440407f4.jpg)
Fig. 5. Isoflurane postconditioning reduced translocation of…
Fig. 5. Isoflurane postconditioning reduced translocation of p65 to nuclei after the middle cerebral arterial…
Fig. 6. Isoflurane posttreatment reduced lipopolysaccharid (LPS)-induced…
Fig. 6. Isoflurane posttreatment reduced lipopolysaccharid (LPS)-induced interleukin (IL)-1β increase in mice
The frontal cerebral…
Fig. 7. Interleukin (IL)-1β deficient mice had…
Fig. 7. Interleukin (IL)-1β deficient mice had better histological and neurological function outcome than wild-type…
Fig. 8. Isoflurane post-treatment failed to induce…
Fig. 8. Isoflurane post-treatment failed to induce neuroprotection in interleukin (IL)-1β deficient mice after middle…
- Isoflurane preconditioning improves short-term and long-term neurological outcome after focal brain ischemia in adult rats.Li L, Zuo Z. Li L, et al. Neuroscience. 2009 Dec 1;164(2):497-506. doi: 10.1016/j.neuroscience.2009.08.011. Epub 2009 Aug 11. Neuroscience. 2009. PMID: 19679170 Free PMC article.
- Inhibition of brain ischemia-caused notch activation in microglia may contribute to isoflurane postconditioning-induced neuroprotection in male rats.Yin J, Li H, Feng C, Zuo Z. Yin J, et al. CNS Neurol Disord Drug Targets. 2014;13(4):718-32. doi: 10.2174/1871527313666140618110837. CNS Neurol Disord Drug Targets. 2014. PMID: 24938773
- Isoflurane postconditioning induces neuroprotection via Akt activation and attenuation of increased mitochondrial membrane permeability.Li L, Zuo Z. Li L, et al. Neuroscience. 2011 Dec 29;199:44-50. doi: 10.1016/j.neuroscience.2011.10.022. Epub 2011 Oct 20. Neuroscience. 2011. PMID: 22040798 Free PMC article.
- Wnt/β-catenin signaling pathway contributes to isoflurane postconditioning against cerebral ischemia-reperfusion injury and is possibly related to the transforming growth factorβ1/Smad3 signaling pathway.Zhang G, Ge M, Han Z, Wang S, Yin J, Peng L, Xu F, Zhang Q, Dai Z, Xie L, Li Y, Si J, Ma K. Zhang G, et al. Biomed Pharmacother. 2019 Feb;110:420-430. doi: 10.1016/j.biopha.2018.11.143. Epub 2018 Dec 5. Biomed Pharmacother. 2019. PMID: 30530044
- [The effects of preconditioning and postconditioning with isoflurane on focal cerebral ischemi/reperfusion injury in rats].Li G, Jia J, Fu J, Wang H, Ji K, Zang B. Li G, et al. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014 Jun;26(6):431-5. doi: 10.3760/cma.j.issn.2095-4352.2014.06.013. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014. PMID: 24912644 Chinese.
- Novel derivatives of eugenol as potent anti-inflammatory agents via PPARγ agonism: rational design, synthesis, analysis, PPARγ protein binding assay and computational studies.Anjum NF, Shanmugarajan D, Shivaraju VK, Faizan S, Naishima NL, Prashantha Kumar BR, Javid S, Purohit MN. Anjum NF, et al. RSC Adv. 2022 Jun 7;12(26):16966-16978. doi: 10.1039/d2ra02116a. eCollection 2022 Jun 1. RSC Adv. 2022. PMID: 35754905 Free PMC article.
- Activation of the Lateral Habenula-Ventral Tegmental Area Neural Circuit Contributes to Postoperative Cognitive Dysfunction in Mice.Xin J, Shan W, Li J, Yu H, Zuo Z. Xin J, et al. Adv Sci (Weinh). 2022 Aug;9(22):e2202228. doi: 10.1002/advs.202202228. Epub 2022 May 26. Adv Sci (Weinh). 2022. PMID: 35616407 Free PMC article.
- Critical role of FPR1 in splenocyte migration into brain to worsen inflammation and ischemic brain injury in mice.Li J, Chordia MD, Zhang Y, Zong H, Pan D, Zuo Z. Li J, et al. Theranostics. 2022 Mar 21;12(7):3024-3044. doi: 10.7150/thno.57218. eCollection 2022. Theranostics. 2022. PMID: 35547761 Free PMC article.
- Dynamics of isoflurane-induced vasodilation and blood flow of cerebral vasculature revealed by multi-exposure speckle imaging.Sullender CT, Richards LM, He F, Luan L, Dunn AK. Sullender CT, et al. J Neurosci Methods. 2022 Jan 15;366:109434. doi: 10.1016/j.jneumeth.2021.109434. Epub 2021 Dec 1. J Neurosci Methods. 2022. PMID: 34863840 Free PMC article.
- Translational challenges of remote ischemic conditioning in ischemic stroke - a systematic review.Hansen LF, Nielsen NSK, Christoffersen LC, Kruuse C. Hansen LF, et al. Ann Clin Transl Neurol. 2021 Aug;8(8):1720-1729. doi: 10.1002/acn3.51405. Epub 2021 Jun 16. Ann Clin Transl Neurol. 2021. PMID: 34133841 Free PMC article.
- Research Support, N.I.H., Extramural
- Animals
- Blotting, Western
- Brain Ischemia / metabolism*
- Brain Ischemia / pathology
- Enzyme-Linked Immunosorbent Assay
- In Situ Nick-End Labeling
- Interleukin-1beta / biosynthesis*
- Ischemic Postconditioning / methods*
- Isoflurane / pharmacology*
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- NF-kappa B / metabolism*
- Neuroprotective Agents / pharmacology*
- Rats
- Rats, Sprague-Dawley
- Recovery of Function / drug effects
- Interleukin-1beta
- NF-kappa B
- Neuroprotective Agents
- Isoflurane
- Full Text Sources
- Other Literature Sources
- Medical
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Fig. 5. Isoflurane postconditioning reduced translocation of…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3628970/bin/nihms440407f5.jpg)
Fig. 6. Isoflurane posttreatment reduced lipopolysaccharid (LPS)-induced…
Fig. 6. Isoflurane posttreatment reduced lipopolysaccharid (LPS)-induced interleukin (IL)-1β increase in mice
The frontal cerebral…
Fig. 7. Interleukin (IL)-1β deficient mice had…
Fig. 7. Interleukin (IL)-1β deficient mice had better histological and neurological function outcome than wild-type…
Fig. 8. Isoflurane post-treatment failed to induce…
Fig. 8. Isoflurane post-treatment failed to induce neuroprotection in interleukin (IL)-1β deficient mice after middle…
- Isoflurane preconditioning improves short-term and long-term neurological outcome after focal brain ischemia in adult rats.Li L, Zuo Z. Li L, et al. Neuroscience. 2009 Dec 1;164(2):497-506. doi: 10.1016/j.neuroscience.2009.08.011. Epub 2009 Aug 11. Neuroscience. 2009. PMID: 19679170 Free PMC article.
- Inhibition of brain ischemia-caused notch activation in microglia may contribute to isoflurane postconditioning-induced neuroprotection in male rats.Yin J, Li H, Feng C, Zuo Z. Yin J, et al. CNS Neurol Disord Drug Targets. 2014;13(4):718-32. doi: 10.2174/1871527313666140618110837. CNS Neurol Disord Drug Targets. 2014. PMID: 24938773
- Isoflurane postconditioning induces neuroprotection via Akt activation and attenuation of increased mitochondrial membrane permeability.Li L, Zuo Z. Li L, et al. Neuroscience. 2011 Dec 29;199:44-50. doi: 10.1016/j.neuroscience.2011.10.022. Epub 2011 Oct 20. Neuroscience. 2011. PMID: 22040798 Free PMC article.
- Wnt/β-catenin signaling pathway contributes to isoflurane postconditioning against cerebral ischemia-reperfusion injury and is possibly related to the transforming growth factorβ1/Smad3 signaling pathway.Zhang G, Ge M, Han Z, Wang S, Yin J, Peng L, Xu F, Zhang Q, Dai Z, Xie L, Li Y, Si J, Ma K. Zhang G, et al. Biomed Pharmacother. 2019 Feb;110:420-430. doi: 10.1016/j.biopha.2018.11.143. Epub 2018 Dec 5. Biomed Pharmacother. 2019. PMID: 30530044
- [The effects of preconditioning and postconditioning with isoflurane on focal cerebral ischemi/reperfusion injury in rats].Li G, Jia J, Fu J, Wang H, Ji K, Zang B. Li G, et al. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014 Jun;26(6):431-5. doi: 10.3760/cma.j.issn.2095-4352.2014.06.013. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014. PMID: 24912644 Chinese.
- Novel derivatives of eugenol as potent anti-inflammatory agents via PPARγ agonism: rational design, synthesis, analysis, PPARγ protein binding assay and computational studies.Anjum NF, Shanmugarajan D, Shivaraju VK, Faizan S, Naishima NL, Prashantha Kumar BR, Javid S, Purohit MN. Anjum NF, et al. RSC Adv. 2022 Jun 7;12(26):16966-16978. doi: 10.1039/d2ra02116a. eCollection 2022 Jun 1. RSC Adv. 2022. PMID: 35754905 Free PMC article.
- Activation of the Lateral Habenula-Ventral Tegmental Area Neural Circuit Contributes to Postoperative Cognitive Dysfunction in Mice.Xin J, Shan W, Li J, Yu H, Zuo Z. Xin J, et al. Adv Sci (Weinh). 2022 Aug;9(22):e2202228. doi: 10.1002/advs.202202228. Epub 2022 May 26. Adv Sci (Weinh). 2022. PMID: 35616407 Free PMC article.
- Critical role of FPR1 in splenocyte migration into brain to worsen inflammation and ischemic brain injury in mice.Li J, Chordia MD, Zhang Y, Zong H, Pan D, Zuo Z. Li J, et al. Theranostics. 2022 Mar 21;12(7):3024-3044. doi: 10.7150/thno.57218. eCollection 2022. Theranostics. 2022. PMID: 35547761 Free PMC article.
- Dynamics of isoflurane-induced vasodilation and blood flow of cerebral vasculature revealed by multi-exposure speckle imaging.Sullender CT, Richards LM, He F, Luan L, Dunn AK. Sullender CT, et al. J Neurosci Methods. 2022 Jan 15;366:109434. doi: 10.1016/j.jneumeth.2021.109434. Epub 2021 Dec 1. J Neurosci Methods. 2022. PMID: 34863840 Free PMC article.
- Translational challenges of remote ischemic conditioning in ischemic stroke - a systematic review.Hansen LF, Nielsen NSK, Christoffersen LC, Kruuse C. Hansen LF, et al. Ann Clin Transl Neurol. 2021 Aug;8(8):1720-1729. doi: 10.1002/acn3.51405. Epub 2021 Jun 16. Ann Clin Transl Neurol. 2021. PMID: 34133841 Free PMC article.
- Research Support, N.I.H., Extramural
- Animals
- Blotting, Western
- Brain Ischemia / metabolism*
- Brain Ischemia / pathology
- Enzyme-Linked Immunosorbent Assay
- In Situ Nick-End Labeling
- Interleukin-1beta / biosynthesis*
- Ischemic Postconditioning / methods*
- Isoflurane / pharmacology*
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- NF-kappa B / metabolism*
- Neuroprotective Agents / pharmacology*
- Rats
- Rats, Sprague-Dawley
- Recovery of Function / drug effects
- Interleukin-1beta
- NF-kappa B
- Neuroprotective Agents
- Isoflurane
- Full Text Sources
- Other Literature Sources
- Medical
![Fig. 6. Isoflurane posttreatment reduced lipopolysaccharid (LPS)-induced…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3628970/bin/nihms440407f6.jpg)
Fig. 7. Interleukin (IL)-1β deficient mice had…
Fig. 7. Interleukin (IL)-1β deficient mice had better histological and neurological function outcome than wild-type…
Fig. 8. Isoflurane post-treatment failed to induce…
Fig. 8. Isoflurane post-treatment failed to induce neuroprotection in interleukin (IL)-1β deficient mice after middle…
![Fig. 7. Interleukin (IL)-1β deficient mice had…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3628970/bin/nihms440407f7.jpg)
![Fig. 8. Isoflurane post-treatment failed to induce…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3628970/bin/nihms440407f8.jpg)
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