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Sevoflurane and Isoflurane induce structural changes in brain vascular endothelial cells and increase blood-brain barrier permeability: Possible link to postoperative delirium and cognitive decline.
Brain Res 2015; 1620:29-41BR

Abstract

A large percentage of patients subjected to general anesthesia at 65 years and older exhibit postoperative delirium (POD). Here, we test the hypothesis that inhaled anesthetics (IAs), such as Sevoflurane and Isoflurane, act directly on brain vascular endothelial cells (BVECs) to increase blood-brain barrier (BBB) permeability, thereby contributing to POD. Rats of young (3-5 months), middle (10-12 months) and old (17-19 months) ages were anesthetized with Sevoflurane or Isoflurane for 3h. After exposure, some were euthanized immediately; others were allowed to recover for 24h before sacrifice. Immunohistochemistry was employed to monitor the extent of BBB breach, and scanning electron microscopy (SEM) was used to examine changes in the luminal surfaces of BVECs. Quantitative immunohistochemistry revealed increased BBB permeability in older animals treated with Sevoflurane, but not Isoflurane. Extravasated immunoglobulin G showed selective affinity for pyramidal neurons. SEM demonstrated marked flattening of the luminal surfaces of BVECs in anesthetic-treated rats. Results suggest an aging-linked BBB compromise resulting from exposure to Sevoflurane. Changes in the luminal surface topology of BVECs indicate a direct effect on the plasma membrane, which may weaken or disrupt their BBB-associated tight junctions. Disruption of brain homeostasis due to plasma influx into the brain parenchyma and binding of plasma components (e.g., immunoglobulins) to neurons may contribute to POD. We propose that, in the elderly, exposure to some IAs can cause BBB compromise that disrupts brain homeostasis, perturbs neuronal function and thereby contributes to POD. If unresolved, this may progress to postoperative cognitive decline and later dementia.

Authors+Show Affiliations

Biomarker Discovery Center, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA; Department of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA.Biomarker Discovery Center, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA; Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08084, USA.Department of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA.Biomarker Discovery Center, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA; Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08084, USA.Biomarker Discovery Center, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA; Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08084, USA.Biomarker Discovery Center, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA; Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08084, USA.Biomarker Discovery Center, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA; Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08084, USA.Biomarker Discovery Center, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA; Department of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA.Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08084, USA; Department of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA.Department of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA.Department of Psychiatry, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA.Philadelphia College of Osteopathic Medicine, , PA, USA, Philadelphia, PA 19131, USA.Biomarker Discovery Center, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA; Department of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA. Electronic address: nagelero@rowan.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25960348

Citation

Acharya, Nimish K., et al. "Sevoflurane and Isoflurane Induce Structural Changes in Brain Vascular Endothelial Cells and Increase Blood-brain Barrier Permeability: Possible Link to Postoperative Delirium and Cognitive Decline." Brain Research, vol. 1620, 2015, pp. 29-41.
Acharya NK, Goldwaser EL, Forsberg MM, et al. Sevoflurane and Isoflurane induce structural changes in brain vascular endothelial cells and increase blood-brain barrier permeability: Possible link to postoperative delirium and cognitive decline. Brain Res. 2015;1620:29-41.
Acharya, N. K., Goldwaser, E. L., Forsberg, M. M., Godsey, G. A., Johnson, C. A., Sarkar, A., ... Nagele, R. G. (2015). Sevoflurane and Isoflurane induce structural changes in brain vascular endothelial cells and increase blood-brain barrier permeability: Possible link to postoperative delirium and cognitive decline. Brain Research, 1620, pp. 29-41. doi:10.1016/j.brainres.2015.04.054.
Acharya NK, et al. Sevoflurane and Isoflurane Induce Structural Changes in Brain Vascular Endothelial Cells and Increase Blood-brain Barrier Permeability: Possible Link to Postoperative Delirium and Cognitive Decline. Brain Res. 2015 Sep 16;1620:29-41. PubMed PMID: 25960348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sevoflurane and Isoflurane induce structural changes in brain vascular endothelial cells and increase blood-brain barrier permeability: Possible link to postoperative delirium and cognitive decline. AU - Acharya,Nimish K, AU - Goldwaser,Eric L, AU - Forsberg,Martin M, AU - Godsey,George A, AU - Johnson,Cristina A, AU - Sarkar,Abhirup, AU - DeMarshall,Cassandra, AU - Kosciuk,Mary C, AU - Dash,Jacqueline M, AU - Hale,Caitlin P, AU - Leonard,Douglas M, AU - Appelt,Denah M, AU - Nagele,Robert G, Y1 - 2015/05/08/ PY - 2015/03/10/received PY - 2015/04/24/revised PY - 2015/04/28/accepted PY - 2015/5/12/entrez PY - 2015/5/12/pubmed PY - 2016/5/18/medline KW - Anesthesia KW - Blood−brain barrier KW - Delirium KW - Isoflurane KW - Postoperative delirium KW - Sevoflurane SP - 29 EP - 41 JF - Brain research JO - Brain Res. VL - 1620 N2 - A large percentage of patients subjected to general anesthesia at 65 years and older exhibit postoperative delirium (POD). Here, we test the hypothesis that inhaled anesthetics (IAs), such as Sevoflurane and Isoflurane, act directly on brain vascular endothelial cells (BVECs) to increase blood-brain barrier (BBB) permeability, thereby contributing to POD. Rats of young (3-5 months), middle (10-12 months) and old (17-19 months) ages were anesthetized with Sevoflurane or Isoflurane for 3h. After exposure, some were euthanized immediately; others were allowed to recover for 24h before sacrifice. Immunohistochemistry was employed to monitor the extent of BBB breach, and scanning electron microscopy (SEM) was used to examine changes in the luminal surfaces of BVECs. Quantitative immunohistochemistry revealed increased BBB permeability in older animals treated with Sevoflurane, but not Isoflurane. Extravasated immunoglobulin G showed selective affinity for pyramidal neurons. SEM demonstrated marked flattening of the luminal surfaces of BVECs in anesthetic-treated rats. Results suggest an aging-linked BBB compromise resulting from exposure to Sevoflurane. Changes in the luminal surface topology of BVECs indicate a direct effect on the plasma membrane, which may weaken or disrupt their BBB-associated tight junctions. Disruption of brain homeostasis due to plasma influx into the brain parenchyma and binding of plasma components (e.g., immunoglobulins) to neurons may contribute to POD. We propose that, in the elderly, exposure to some IAs can cause BBB compromise that disrupts brain homeostasis, perturbs neuronal function and thereby contributes to POD. If unresolved, this may progress to postoperative cognitive decline and later dementia. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/25960348/Sevoflurane_and_Isoflurane_induce_structural_changes_in_brain_vascular_endothelial_cells_and_increase_blood_brain_barrier_permeability:_Possible_link_to_postoperative_delirium_and_cognitive_decline_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(15)00368-6 DB - PRIME DP - Unbound Medicine ER -