Isoflurane induces learning impairment that is mediated by interleukin 1β in rodents
Lin Cao, Liaoliao Li, Daowei Lin, Zhiyi Zuo, Lin Cao, Liaoliao Li, Daowei Lin, Zhiyi Zuo
Abstract
Postoperative cognitive decline is a clinical syndrome. Volatile anesthetics are commonly used during surgery. It is conceivable that volatile anesthetics may contribute to postoperative cognitive decline. Isoflurane can impair cognitive functions of animals under certain conditions. However, the mechanisms for this impairment are not clear. Here, male 18-month old Fisher 344 rats or 10-week old mice were exposed to 1.2 or 1.4% isoflurane for 2 h. Our studies showed that isoflurane impaired the cognitive functions of the rats in Barnes maze. Isoflurane-exposed rats had reduced freezing behavior during the training sessions in the fear conditioning test. This isoflurane effect was attenuated by lidocaine, a local anesthetic with anti-inflammatory property. Rats that had training sessions and were exposed to isoflurane 30 min later had freezing behavior similar to that of control animals. Isoflurane increased the expression of interleukin 1β (IL-1β), interleukin-6 and activated caspase 3 in the hippocampus of the 18-month old rats. IL-1β positive staining was co-localized with that of NeuN, a neuronal marker. The increase of IL-1β and activated caspase 3 but not interleukin-6 was attenuated by lidocaine. Isoflurane also impaired the cognitive functions of 10-week old C57BL/6J mice and increased IL-1β in their hippocampi. However, isoflurane did not affect the cognitive functions of IL-1β deficient mice. Our results suggest that isoflurane impairs the learning but may not affect the recall of the aged rats. IL-1β may play an important role in this isoflurane effect.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
![Figure 1. Isoflurane-induced cognitive impairment measured by…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3520904/bin/pone.0051431.g001.jpg)
Figure 2. Isoflurane-induced learning impairment measured by…
Figure 2. Isoflurane-induced learning impairment measured by fear conditioning test.
A: freezing behavior during training…
Figure 3. Isoflurane effects on interleukin 1β…
Figure 3. Isoflurane effects on interleukin 1β (IL-1β) and tumor necrosis factor α (TNFα) contents…
Figure 4. Isoflurane effects on the expression…
Figure 4. Isoflurane effects on the expression of interleukin 6 (IL-6), activated/cleaved caspase 3 and…
Figure 5. Isoflurane effects on the expression…
Figure 5. Isoflurane effects on the expression of interleukin 6 (IL-6), activated/cleaved caspase 3 and…
Figure 6. Expression of interleukin 1β (IL-1β),…
Figure 6. Expression of interleukin 1β (IL-1β), IL-6 and activated/cleaved caspase 3 in rat brain…
Figure 7. Isoflurane effects on the expression…
Figure 7. Isoflurane effects on the expression of NeuN, drebrin and synaptophysin in rat brain…
Figure 8. Isoflurane effects on cognitive functions…
Figure 8. Isoflurane effects on cognitive functions assessed by fear conditioning.
Ten-week old male C57BL/6J…
- Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats.Lin D, Zuo Z. Lin D, et al. Neuropharmacology. 2011 Dec;61(8):1354-9. doi: 10.1016/j.neuropharm.2011.08.011. Epub 2011 Aug 16. Neuropharmacology. 2011. PMID: 21864548 Free PMC article.
- Lidocaine attenuates cognitive impairment after isoflurane anesthesia in old rats.Lin D, Cao L, Wang Z, Li J, Washington JM, Zuo Z. Lin D, et al. Behav Brain Res. 2012 Mar 17;228(2):319-27. doi: 10.1016/j.bbr.2011.12.010. Epub 2011 Dec 16. Behav Brain Res. 2012. PMID: 22192381 Free PMC article.
- The choice of general anesthetics may not affect neuroinflammation and impairment of learning and memory after surgery in elderly rats.Zhang J, Tan H, Jiang W, Zuo Z. Zhang J, et al. J Neuroimmune Pharmacol. 2015 Mar;10(1):179-89. doi: 10.1007/s11481-014-9580-y. Epub 2015 Feb 4. J Neuroimmune Pharmacol. 2015. PMID: 25649847
- Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery.Zheng B, Lai R, Li J, Zuo Z. Zheng B, et al. Brain Behav Immun. 2017 Mar;61:365-374. doi: 10.1016/j.bbi.2017.01.005. Epub 2017 Jan 10. Brain Behav Immun. 2017. PMID: 28089560 Free PMC article.
- Critical role of inflammatory cytokines in impairing biochemical processes for learning and memory after surgery in rats.Tan H, Cao J, Zhang J, Zuo Z. Tan H, et al. J Neuroinflammation. 2014 May 22;11:93. doi: 10.1186/1742-2094-11-93. J Neuroinflammation. 2014. PMID: 24884762 Free PMC article.
- Protective effects of chlorogenic acid on isoflurane-induced cognitive impairment of aged mice.Chong H, Xi Y, Zhou Y, Wang G. Chong H, et al. Food Sci Nutr. 2022 Jun 20;10(10):3492-3500. doi: 10.1002/fsn3.2952. eCollection 2022 Oct. Food Sci Nutr. 2022. PMID: 36249964 Free PMC article.
- Do We Have Measures to Reduce Post-operative Cognitive Dysfunction?Valdelievre T, Zuo Z. Valdelievre T, et al. Front Neurosci. 2022 Jun 2;16:850012. doi: 10.3389/fnins.2022.850012. eCollection 2022. Front Neurosci. 2022. PMID: 35720718 Free PMC article. No abstract available.
- Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice.Peng L, Liu S, Xu J, Xie W, Fang X, Xia T, Gu X. Peng L, et al. Int Immunopharmacol. 2022 Aug;109:108903. doi: 10.1016/j.intimp.2022.108903. Epub 2022 Jun 13. Int Immunopharmacol. 2022. PMID: 35709590 Free PMC article.
- Cerebral Glutamate Regulation and Receptor Changes in Perioperative Neuroinflammation and Cognitive Dysfunction.Zhang Y, Chu JM, Wong GT. Zhang Y, et al. Biomolecules. 2022 Apr 18;12(4):597. doi: 10.3390/biom12040597. Biomolecules. 2022. PMID: 35454185 Free PMC article. Review.
- Gut-Brain Axis: Possible Role of Gut Microbiota in Perioperative Neurocognitive Disorders.Wang XQ, Li H, Li XN, Yuan CH, Zhao H. Wang XQ, et al. Front Aging Neurosci. 2021 Dec 22;13:745774. doi: 10.3389/fnagi.2021.745774. eCollection 2021. Front Aging Neurosci. 2021. PMID: 35002672 Free PMC article. Review.
-
- Silva AC, ORyan F, Poor DB (2006) Postoperative nausea and vomiting (PONV) after orthognathic surgery: a retrospective study and literature review. J Oral Maxillofac Surg 64: 1385–1397. - PubMed
-
- Zheng S, Zuo Z (2004) Isoflurane preconditioning induces neuroprotection against ischemia via activation of p38 mitogen-activated protein kinase. Mol Pharmacol 65: 1172–1180. - PubMed
-
- Culley DJ, Baxter M, Yukhananov R, Crosby G (2003) The memory effects of general anesthesia persist for weeks in young and aged rats. Anesth Analg 96: 1004–1009. - PubMed
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Animals
- Antigens, Nuclear / metabolism
- CD11b Antigen / metabolism
- Caspase 3 / metabolism
- Cognition / drug effects
- Conditioning, Psychological / drug effects
- Enzyme Activation / drug effects
- Fear / drug effects
- Hippocampus / drug effects
- Hippocampus / enzymology
- Hippocampus / pathology
- Hippocampus / physiopathology
- Inhalation Exposure
- Interleukin-1beta / metabolism*
- Interleukin-6 / metabolism
- Isoflurane / administration & dosage
- Isoflurane / pharmacology*
- Learning Disabilities / metabolism*
- Learning Disabilities / pathology*
- Learning Disabilities / physiopathology
- Male
- Maze Learning
- Mental Recall / drug effects
- Mice
- Mice, Inbred C57BL
- Nerve Tissue Proteins / metabolism
- Neuropeptides / metabolism
- Rats
- Rats, Inbred F344
- Synaptophysin / metabolism
- Tumor Necrosis Factor-alpha / metabolism
- Antigens, Nuclear
- CD11b Antigen
- Interleukin-1beta
- Interleukin-6
- Nerve Tissue Proteins
- Neuropeptides
- Rbfox3 protein, rat
- Synaptophysin
- Tumor Necrosis Factor-alpha
- drebrins
- Isoflurane
- Caspase 3
- Full Text Sources
- Medical
- Molecular Biology Databases
- Research Materials
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
![Figure 2. Isoflurane-induced learning impairment measured by…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3520904/bin/pone.0051431.g002.jpg)
Figure 3. Isoflurane effects on interleukin 1β…
Figure 3. Isoflurane effects on interleukin 1β (IL-1β) and tumor necrosis factor α (TNFα) contents…
Figure 4. Isoflurane effects on the expression…
Figure 4. Isoflurane effects on the expression of interleukin 6 (IL-6), activated/cleaved caspase 3 and…
Figure 5. Isoflurane effects on the expression…
Figure 5. Isoflurane effects on the expression of interleukin 6 (IL-6), activated/cleaved caspase 3 and…
Figure 6. Expression of interleukin 1β (IL-1β),…
Figure 6. Expression of interleukin 1β (IL-1β), IL-6 and activated/cleaved caspase 3 in rat brain…
Figure 7. Isoflurane effects on the expression…
Figure 7. Isoflurane effects on the expression of NeuN, drebrin and synaptophysin in rat brain…
Figure 8. Isoflurane effects on cognitive functions…
Figure 8. Isoflurane effects on cognitive functions assessed by fear conditioning.
Ten-week old male C57BL/6J…
- Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats.Lin D, Zuo Z. Lin D, et al. Neuropharmacology. 2011 Dec;61(8):1354-9. doi: 10.1016/j.neuropharm.2011.08.011. Epub 2011 Aug 16. Neuropharmacology. 2011. PMID: 21864548 Free PMC article.
- Lidocaine attenuates cognitive impairment after isoflurane anesthesia in old rats.Lin D, Cao L, Wang Z, Li J, Washington JM, Zuo Z. Lin D, et al. Behav Brain Res. 2012 Mar 17;228(2):319-27. doi: 10.1016/j.bbr.2011.12.010. Epub 2011 Dec 16. Behav Brain Res. 2012. PMID: 22192381 Free PMC article.
- The choice of general anesthetics may not affect neuroinflammation and impairment of learning and memory after surgery in elderly rats.Zhang J, Tan H, Jiang W, Zuo Z. Zhang J, et al. J Neuroimmune Pharmacol. 2015 Mar;10(1):179-89. doi: 10.1007/s11481-014-9580-y. Epub 2015 Feb 4. J Neuroimmune Pharmacol. 2015. PMID: 25649847
- Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery.Zheng B, Lai R, Li J, Zuo Z. Zheng B, et al. Brain Behav Immun. 2017 Mar;61:365-374. doi: 10.1016/j.bbi.2017.01.005. Epub 2017 Jan 10. Brain Behav Immun. 2017. PMID: 28089560 Free PMC article.
- Critical role of inflammatory cytokines in impairing biochemical processes for learning and memory after surgery in rats.Tan H, Cao J, Zhang J, Zuo Z. Tan H, et al. J Neuroinflammation. 2014 May 22;11:93. doi: 10.1186/1742-2094-11-93. J Neuroinflammation. 2014. PMID: 24884762 Free PMC article.
- Protective effects of chlorogenic acid on isoflurane-induced cognitive impairment of aged mice.Chong H, Xi Y, Zhou Y, Wang G. Chong H, et al. Food Sci Nutr. 2022 Jun 20;10(10):3492-3500. doi: 10.1002/fsn3.2952. eCollection 2022 Oct. Food Sci Nutr. 2022. PMID: 36249964 Free PMC article.
- Do We Have Measures to Reduce Post-operative Cognitive Dysfunction?Valdelievre T, Zuo Z. Valdelievre T, et al. Front Neurosci. 2022 Jun 2;16:850012. doi: 10.3389/fnins.2022.850012. eCollection 2022. Front Neurosci. 2022. PMID: 35720718 Free PMC article. No abstract available.
- Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice.Peng L, Liu S, Xu J, Xie W, Fang X, Xia T, Gu X. Peng L, et al. Int Immunopharmacol. 2022 Aug;109:108903. doi: 10.1016/j.intimp.2022.108903. Epub 2022 Jun 13. Int Immunopharmacol. 2022. PMID: 35709590 Free PMC article.
- Cerebral Glutamate Regulation and Receptor Changes in Perioperative Neuroinflammation and Cognitive Dysfunction.Zhang Y, Chu JM, Wong GT. Zhang Y, et al. Biomolecules. 2022 Apr 18;12(4):597. doi: 10.3390/biom12040597. Biomolecules. 2022. PMID: 35454185 Free PMC article. Review.
- Gut-Brain Axis: Possible Role of Gut Microbiota in Perioperative Neurocognitive Disorders.Wang XQ, Li H, Li XN, Yuan CH, Zhao H. Wang XQ, et al. Front Aging Neurosci. 2021 Dec 22;13:745774. doi: 10.3389/fnagi.2021.745774. eCollection 2021. Front Aging Neurosci. 2021. PMID: 35002672 Free PMC article. Review.
-
- Silva AC, ORyan F, Poor DB (2006) Postoperative nausea and vomiting (PONV) after orthognathic surgery: a retrospective study and literature review. J Oral Maxillofac Surg 64: 1385–1397. - PubMed
-
- Zheng S, Zuo Z (2004) Isoflurane preconditioning induces neuroprotection against ischemia via activation of p38 mitogen-activated protein kinase. Mol Pharmacol 65: 1172–1180. - PubMed
-
- Culley DJ, Baxter M, Yukhananov R, Crosby G (2003) The memory effects of general anesthesia persist for weeks in young and aged rats. Anesth Analg 96: 1004–1009. - PubMed
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Animals
- Antigens, Nuclear / metabolism
- CD11b Antigen / metabolism
- Caspase 3 / metabolism
- Cognition / drug effects
- Conditioning, Psychological / drug effects
- Enzyme Activation / drug effects
- Fear / drug effects
- Hippocampus / drug effects
- Hippocampus / enzymology
- Hippocampus / pathology
- Hippocampus / physiopathology
- Inhalation Exposure
- Interleukin-1beta / metabolism*
- Interleukin-6 / metabolism
- Isoflurane / administration & dosage
- Isoflurane / pharmacology*
- Learning Disabilities / metabolism*
- Learning Disabilities / pathology*
- Learning Disabilities / physiopathology
- Male
- Maze Learning
- Mental Recall / drug effects
- Mice
- Mice, Inbred C57BL
- Nerve Tissue Proteins / metabolism
- Neuropeptides / metabolism
- Rats
- Rats, Inbred F344
- Synaptophysin / metabolism
- Tumor Necrosis Factor-alpha / metabolism
- Antigens, Nuclear
- CD11b Antigen
- Interleukin-1beta
- Interleukin-6
- Nerve Tissue Proteins
- Neuropeptides
- Rbfox3 protein, rat
- Synaptophysin
- Tumor Necrosis Factor-alpha
- drebrins
- Isoflurane
- Caspase 3
- Full Text Sources
- Medical
- Molecular Biology Databases
- Research Materials
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
![Figure 3. Isoflurane effects on interleukin 1β…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3520904/bin/pone.0051431.g003.jpg)
Figure 4. Isoflurane effects on the expression…
Figure 4. Isoflurane effects on the expression of interleukin 6 (IL-6), activated/cleaved caspase 3 and…
Figure 5. Isoflurane effects on the expression…
Figure 5. Isoflurane effects on the expression of interleukin 6 (IL-6), activated/cleaved caspase 3 and…
Figure 6. Expression of interleukin 1β (IL-1β),…
Figure 6. Expression of interleukin 1β (IL-1β), IL-6 and activated/cleaved caspase 3 in rat brain…
Figure 7. Isoflurane effects on the expression…
Figure 7. Isoflurane effects on the expression of NeuN, drebrin and synaptophysin in rat brain…
Figure 8. Isoflurane effects on cognitive functions…
Figure 8. Isoflurane effects on cognitive functions assessed by fear conditioning.
Ten-week old male C57BL/6J…
- Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats.Lin D, Zuo Z. Lin D, et al. Neuropharmacology. 2011 Dec;61(8):1354-9. doi: 10.1016/j.neuropharm.2011.08.011. Epub 2011 Aug 16. Neuropharmacology. 2011. PMID: 21864548 Free PMC article.
- Lidocaine attenuates cognitive impairment after isoflurane anesthesia in old rats.Lin D, Cao L, Wang Z, Li J, Washington JM, Zuo Z. Lin D, et al. Behav Brain Res. 2012 Mar 17;228(2):319-27. doi: 10.1016/j.bbr.2011.12.010. Epub 2011 Dec 16. Behav Brain Res. 2012. PMID: 22192381 Free PMC article.
- The choice of general anesthetics may not affect neuroinflammation and impairment of learning and memory after surgery in elderly rats.Zhang J, Tan H, Jiang W, Zuo Z. Zhang J, et al. J Neuroimmune Pharmacol. 2015 Mar;10(1):179-89. doi: 10.1007/s11481-014-9580-y. Epub 2015 Feb 4. J Neuroimmune Pharmacol. 2015. PMID: 25649847
- Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery.Zheng B, Lai R, Li J, Zuo Z. Zheng B, et al. Brain Behav Immun. 2017 Mar;61:365-374. doi: 10.1016/j.bbi.2017.01.005. Epub 2017 Jan 10. Brain Behav Immun. 2017. PMID: 28089560 Free PMC article.
- Critical role of inflammatory cytokines in impairing biochemical processes for learning and memory after surgery in rats.Tan H, Cao J, Zhang J, Zuo Z. Tan H, et al. J Neuroinflammation. 2014 May 22;11:93. doi: 10.1186/1742-2094-11-93. J Neuroinflammation. 2014. PMID: 24884762 Free PMC article.
- Protective effects of chlorogenic acid on isoflurane-induced cognitive impairment of aged mice.Chong H, Xi Y, Zhou Y, Wang G. Chong H, et al. Food Sci Nutr. 2022 Jun 20;10(10):3492-3500. doi: 10.1002/fsn3.2952. eCollection 2022 Oct. Food Sci Nutr. 2022. PMID: 36249964 Free PMC article.
- Do We Have Measures to Reduce Post-operative Cognitive Dysfunction?Valdelievre T, Zuo Z. Valdelievre T, et al. Front Neurosci. 2022 Jun 2;16:850012. doi: 10.3389/fnins.2022.850012. eCollection 2022. Front Neurosci. 2022. PMID: 35720718 Free PMC article. No abstract available.
- Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice.Peng L, Liu S, Xu J, Xie W, Fang X, Xia T, Gu X. Peng L, et al. Int Immunopharmacol. 2022 Aug;109:108903. doi: 10.1016/j.intimp.2022.108903. Epub 2022 Jun 13. Int Immunopharmacol. 2022. PMID: 35709590 Free PMC article.
- Cerebral Glutamate Regulation and Receptor Changes in Perioperative Neuroinflammation and Cognitive Dysfunction.Zhang Y, Chu JM, Wong GT. Zhang Y, et al. Biomolecules. 2022 Apr 18;12(4):597. doi: 10.3390/biom12040597. Biomolecules. 2022. PMID: 35454185 Free PMC article. Review.
- Gut-Brain Axis: Possible Role of Gut Microbiota in Perioperative Neurocognitive Disorders.Wang XQ, Li H, Li XN, Yuan CH, Zhao H. Wang XQ, et al. Front Aging Neurosci. 2021 Dec 22;13:745774. doi: 10.3389/fnagi.2021.745774. eCollection 2021. Front Aging Neurosci. 2021. PMID: 35002672 Free PMC article. Review.
-
- Silva AC, ORyan F, Poor DB (2006) Postoperative nausea and vomiting (PONV) after orthognathic surgery: a retrospective study and literature review. J Oral Maxillofac Surg 64: 1385–1397. - PubMed
-
- Zheng S, Zuo Z (2004) Isoflurane preconditioning induces neuroprotection against ischemia via activation of p38 mitogen-activated protein kinase. Mol Pharmacol 65: 1172–1180. - PubMed
-
- Culley DJ, Baxter M, Yukhananov R, Crosby G (2003) The memory effects of general anesthesia persist for weeks in young and aged rats. Anesth Analg 96: 1004–1009. - PubMed
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Animals
- Antigens, Nuclear / metabolism
- CD11b Antigen / metabolism
- Caspase 3 / metabolism
- Cognition / drug effects
- Conditioning, Psychological / drug effects
- Enzyme Activation / drug effects
- Fear / drug effects
- Hippocampus / drug effects
- Hippocampus / enzymology
- Hippocampus / pathology
- Hippocampus / physiopathology
- Inhalation Exposure
- Interleukin-1beta / metabolism*
- Interleukin-6 / metabolism
- Isoflurane / administration & dosage
- Isoflurane / pharmacology*
- Learning Disabilities / metabolism*
- Learning Disabilities / pathology*
- Learning Disabilities / physiopathology
- Male
- Maze Learning
- Mental Recall / drug effects
- Mice
- Mice, Inbred C57BL
- Nerve Tissue Proteins / metabolism
- Neuropeptides / metabolism
- Rats
- Rats, Inbred F344
- Synaptophysin / metabolism
- Tumor Necrosis Factor-alpha / metabolism
- Antigens, Nuclear
- CD11b Antigen
- Interleukin-1beta
- Interleukin-6
- Nerve Tissue Proteins
- Neuropeptides
- Rbfox3 protein, rat
- Synaptophysin
- Tumor Necrosis Factor-alpha
- drebrins
- Isoflurane
- Caspase 3
- Full Text Sources
- Medical
- Molecular Biology Databases
- Research Materials
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
![Figure 4. Isoflurane effects on the expression…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3520904/bin/pone.0051431.g004.jpg)
Figure 5. Isoflurane effects on the expression…
Figure 5. Isoflurane effects on the expression of interleukin 6 (IL-6), activated/cleaved caspase 3 and…
Figure 6. Expression of interleukin 1β (IL-1β),…
Figure 6. Expression of interleukin 1β (IL-1β), IL-6 and activated/cleaved caspase 3 in rat brain…
Figure 7. Isoflurane effects on the expression…
Figure 7. Isoflurane effects on the expression of NeuN, drebrin and synaptophysin in rat brain…
Figure 8. Isoflurane effects on cognitive functions…
Figure 8. Isoflurane effects on cognitive functions assessed by fear conditioning.
Ten-week old male C57BL/6J…
- Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats.Lin D, Zuo Z. Lin D, et al. Neuropharmacology. 2011 Dec;61(8):1354-9. doi: 10.1016/j.neuropharm.2011.08.011. Epub 2011 Aug 16. Neuropharmacology. 2011. PMID: 21864548 Free PMC article.
- Lidocaine attenuates cognitive impairment after isoflurane anesthesia in old rats.Lin D, Cao L, Wang Z, Li J, Washington JM, Zuo Z. Lin D, et al. Behav Brain Res. 2012 Mar 17;228(2):319-27. doi: 10.1016/j.bbr.2011.12.010. Epub 2011 Dec 16. Behav Brain Res. 2012. PMID: 22192381 Free PMC article.
- The choice of general anesthetics may not affect neuroinflammation and impairment of learning and memory after surgery in elderly rats.Zhang J, Tan H, Jiang W, Zuo Z. Zhang J, et al. J Neuroimmune Pharmacol. 2015 Mar;10(1):179-89. doi: 10.1007/s11481-014-9580-y. Epub 2015 Feb 4. J Neuroimmune Pharmacol. 2015. PMID: 25649847
- Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery.Zheng B, Lai R, Li J, Zuo Z. Zheng B, et al. Brain Behav Immun. 2017 Mar;61:365-374. doi: 10.1016/j.bbi.2017.01.005. Epub 2017 Jan 10. Brain Behav Immun. 2017. PMID: 28089560 Free PMC article.
- Critical role of inflammatory cytokines in impairing biochemical processes for learning and memory after surgery in rats.Tan H, Cao J, Zhang J, Zuo Z. Tan H, et al. J Neuroinflammation. 2014 May 22;11:93. doi: 10.1186/1742-2094-11-93. J Neuroinflammation. 2014. PMID: 24884762 Free PMC article.
- Protective effects of chlorogenic acid on isoflurane-induced cognitive impairment of aged mice.Chong H, Xi Y, Zhou Y, Wang G. Chong H, et al. Food Sci Nutr. 2022 Jun 20;10(10):3492-3500. doi: 10.1002/fsn3.2952. eCollection 2022 Oct. Food Sci Nutr. 2022. PMID: 36249964 Free PMC article.
- Do We Have Measures to Reduce Post-operative Cognitive Dysfunction?Valdelievre T, Zuo Z. Valdelievre T, et al. Front Neurosci. 2022 Jun 2;16:850012. doi: 10.3389/fnins.2022.850012. eCollection 2022. Front Neurosci. 2022. PMID: 35720718 Free PMC article. No abstract available.
- Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice.Peng L, Liu S, Xu J, Xie W, Fang X, Xia T, Gu X. Peng L, et al. Int Immunopharmacol. 2022 Aug;109:108903. doi: 10.1016/j.intimp.2022.108903. Epub 2022 Jun 13. Int Immunopharmacol. 2022. PMID: 35709590 Free PMC article.
- Cerebral Glutamate Regulation and Receptor Changes in Perioperative Neuroinflammation and Cognitive Dysfunction.Zhang Y, Chu JM, Wong GT. Zhang Y, et al. Biomolecules. 2022 Apr 18;12(4):597. doi: 10.3390/biom12040597. Biomolecules. 2022. PMID: 35454185 Free PMC article. Review.
- Gut-Brain Axis: Possible Role of Gut Microbiota in Perioperative Neurocognitive Disorders.Wang XQ, Li H, Li XN, Yuan CH, Zhao H. Wang XQ, et al. Front Aging Neurosci. 2021 Dec 22;13:745774. doi: 10.3389/fnagi.2021.745774. eCollection 2021. Front Aging Neurosci. 2021. PMID: 35002672 Free PMC article. Review.
-
- Silva AC, ORyan F, Poor DB (2006) Postoperative nausea and vomiting (PONV) after orthognathic surgery: a retrospective study and literature review. J Oral Maxillofac Surg 64: 1385–1397. - PubMed
-
- Zheng S, Zuo Z (2004) Isoflurane preconditioning induces neuroprotection against ischemia via activation of p38 mitogen-activated protein kinase. Mol Pharmacol 65: 1172–1180. - PubMed
-
- Culley DJ, Baxter M, Yukhananov R, Crosby G (2003) The memory effects of general anesthesia persist for weeks in young and aged rats. Anesth Analg 96: 1004–1009. - PubMed
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Animals
- Antigens, Nuclear / metabolism
- CD11b Antigen / metabolism
- Caspase 3 / metabolism
- Cognition / drug effects
- Conditioning, Psychological / drug effects
- Enzyme Activation / drug effects
- Fear / drug effects
- Hippocampus / drug effects
- Hippocampus / enzymology
- Hippocampus / pathology
- Hippocampus / physiopathology
- Inhalation Exposure
- Interleukin-1beta / metabolism*
- Interleukin-6 / metabolism
- Isoflurane / administration & dosage
- Isoflurane / pharmacology*
- Learning Disabilities / metabolism*
- Learning Disabilities / pathology*
- Learning Disabilities / physiopathology
- Male
- Maze Learning
- Mental Recall / drug effects
- Mice
- Mice, Inbred C57BL
- Nerve Tissue Proteins / metabolism
- Neuropeptides / metabolism
- Rats
- Rats, Inbred F344
- Synaptophysin / metabolism
- Tumor Necrosis Factor-alpha / metabolism
- Antigens, Nuclear
- CD11b Antigen
- Interleukin-1beta
- Interleukin-6
- Nerve Tissue Proteins
- Neuropeptides
- Rbfox3 protein, rat
- Synaptophysin
- Tumor Necrosis Factor-alpha
- drebrins
- Isoflurane
- Caspase 3
- Full Text Sources
- Medical
- Molecular Biology Databases
- Research Materials
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
![Figure 5. Isoflurane effects on the expression…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3520904/bin/pone.0051431.g005.jpg)
Figure 6. Expression of interleukin 1β (IL-1β),…
Figure 6. Expression of interleukin 1β (IL-1β), IL-6 and activated/cleaved caspase 3 in rat brain…
Figure 7. Isoflurane effects on the expression…
Figure 7. Isoflurane effects on the expression of NeuN, drebrin and synaptophysin in rat brain…
Figure 8. Isoflurane effects on cognitive functions…
Figure 8. Isoflurane effects on cognitive functions assessed by fear conditioning.
Ten-week old male C57BL/6J…
- Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats.Lin D, Zuo Z. Lin D, et al. Neuropharmacology. 2011 Dec;61(8):1354-9. doi: 10.1016/j.neuropharm.2011.08.011. Epub 2011 Aug 16. Neuropharmacology. 2011. PMID: 21864548 Free PMC article.
- Lidocaine attenuates cognitive impairment after isoflurane anesthesia in old rats.Lin D, Cao L, Wang Z, Li J, Washington JM, Zuo Z. Lin D, et al. Behav Brain Res. 2012 Mar 17;228(2):319-27. doi: 10.1016/j.bbr.2011.12.010. Epub 2011 Dec 16. Behav Brain Res. 2012. PMID: 22192381 Free PMC article.
- The choice of general anesthetics may not affect neuroinflammation and impairment of learning and memory after surgery in elderly rats.Zhang J, Tan H, Jiang W, Zuo Z. Zhang J, et al. J Neuroimmune Pharmacol. 2015 Mar;10(1):179-89. doi: 10.1007/s11481-014-9580-y. Epub 2015 Feb 4. J Neuroimmune Pharmacol. 2015. PMID: 25649847
- Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery.Zheng B, Lai R, Li J, Zuo Z. Zheng B, et al. Brain Behav Immun. 2017 Mar;61:365-374. doi: 10.1016/j.bbi.2017.01.005. Epub 2017 Jan 10. Brain Behav Immun. 2017. PMID: 28089560 Free PMC article.
- Critical role of inflammatory cytokines in impairing biochemical processes for learning and memory after surgery in rats.Tan H, Cao J, Zhang J, Zuo Z. Tan H, et al. J Neuroinflammation. 2014 May 22;11:93. doi: 10.1186/1742-2094-11-93. J Neuroinflammation. 2014. PMID: 24884762 Free PMC article.
- Protective effects of chlorogenic acid on isoflurane-induced cognitive impairment of aged mice.Chong H, Xi Y, Zhou Y, Wang G. Chong H, et al. Food Sci Nutr. 2022 Jun 20;10(10):3492-3500. doi: 10.1002/fsn3.2952. eCollection 2022 Oct. Food Sci Nutr. 2022. PMID: 36249964 Free PMC article.
- Do We Have Measures to Reduce Post-operative Cognitive Dysfunction?Valdelievre T, Zuo Z. Valdelievre T, et al. Front Neurosci. 2022 Jun 2;16:850012. doi: 10.3389/fnins.2022.850012. eCollection 2022. Front Neurosci. 2022. PMID: 35720718 Free PMC article. No abstract available.
- Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice.Peng L, Liu S, Xu J, Xie W, Fang X, Xia T, Gu X. Peng L, et al. Int Immunopharmacol. 2022 Aug;109:108903. doi: 10.1016/j.intimp.2022.108903. Epub 2022 Jun 13. Int Immunopharmacol. 2022. PMID: 35709590 Free PMC article.
- Cerebral Glutamate Regulation and Receptor Changes in Perioperative Neuroinflammation and Cognitive Dysfunction.Zhang Y, Chu JM, Wong GT. Zhang Y, et al. Biomolecules. 2022 Apr 18;12(4):597. doi: 10.3390/biom12040597. Biomolecules. 2022. PMID: 35454185 Free PMC article. Review.
- Gut-Brain Axis: Possible Role of Gut Microbiota in Perioperative Neurocognitive Disorders.Wang XQ, Li H, Li XN, Yuan CH, Zhao H. Wang XQ, et al. Front Aging Neurosci. 2021 Dec 22;13:745774. doi: 10.3389/fnagi.2021.745774. eCollection 2021. Front Aging Neurosci. 2021. PMID: 35002672 Free PMC article. Review.
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- Silva AC, ORyan F, Poor DB (2006) Postoperative nausea and vomiting (PONV) after orthognathic surgery: a retrospective study and literature review. J Oral Maxillofac Surg 64: 1385–1397. - PubMed
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- Zheng S, Zuo Z (2004) Isoflurane preconditioning induces neuroprotection against ischemia via activation of p38 mitogen-activated protein kinase. Mol Pharmacol 65: 1172–1180. - PubMed
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- Culley DJ, Baxter M, Yukhananov R, Crosby G (2003) The memory effects of general anesthesia persist for weeks in young and aged rats. Anesth Analg 96: 1004–1009. - PubMed
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Animals
- Antigens, Nuclear / metabolism
- CD11b Antigen / metabolism
- Caspase 3 / metabolism
- Cognition / drug effects
- Conditioning, Psychological / drug effects
- Enzyme Activation / drug effects
- Fear / drug effects
- Hippocampus / drug effects
- Hippocampus / enzymology
- Hippocampus / pathology
- Hippocampus / physiopathology
- Inhalation Exposure
- Interleukin-1beta / metabolism*
- Interleukin-6 / metabolism
- Isoflurane / administration & dosage
- Isoflurane / pharmacology*
- Learning Disabilities / metabolism*
- Learning Disabilities / pathology*
- Learning Disabilities / physiopathology
- Male
- Maze Learning
- Mental Recall / drug effects
- Mice
- Mice, Inbred C57BL
- Nerve Tissue Proteins / metabolism
- Neuropeptides / metabolism
- Rats
- Rats, Inbred F344
- Synaptophysin / metabolism
- Tumor Necrosis Factor-alpha / metabolism
- Antigens, Nuclear
- CD11b Antigen
- Interleukin-1beta
- Interleukin-6
- Nerve Tissue Proteins
- Neuropeptides
- Rbfox3 protein, rat
- Synaptophysin
- Tumor Necrosis Factor-alpha
- drebrins
- Isoflurane
- Caspase 3
- Full Text Sources
- Medical
- Molecular Biology Databases
- Research Materials
![Figure 6. Expression of interleukin 1β (IL-1β),…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3520904/bin/pone.0051431.g006.jpg)
![Figure 7. Isoflurane effects on the expression…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3520904/bin/pone.0051431.g007.jpg)
![Figure 8. Isoflurane effects on cognitive functions…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3520904/bin/pone.0051431.g008.jpg)
References
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- Zheng S, Zuo Z (2004) Isoflurane preconditioning induces neuroprotection against ischemia via activation of p38 mitogen-activated protein kinase. Mol Pharmacol 65: 1172–1180.
- Lin D, Zuo Z (2011) Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats. Neuropharmacology 61: 1354–1359.
- Culley DJ, Baxter M, Yukhananov R, Crosby G (2003) The memory effects of general anesthesia persist for weeks in young and aged rats. Anesth Analg 96: 1004–1009.
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Source: PubMed