Isoflurane induces endothelial apoptosis of the post-hypoxic blood-brain barrier in a transdifferentiated human umbilical vein endothelial cell model.
Isoflurane is a popular volatile anesthetic agent used in humans as well as in experimental animal research. In previous animal studies of the blood-brain barrier (BBB), observations towards an increased permeability after exposure to isoflurane are reported. In this study we investigated the effect...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3377664?pdf=render |
| _version_ | 1819265128130936832 |
|---|---|
| author | Michael S Dittmar Walter Petermichl Felix Schlachetzki Bernhard M Graf Michael Gruber |
| author_facet | Michael S Dittmar Walter Petermichl Felix Schlachetzki Bernhard M Graf Michael Gruber |
| author_sort | Michael S Dittmar |
| collection | DOAJ |
| description | Isoflurane is a popular volatile anesthetic agent used in humans as well as in experimental animal research. In previous animal studies of the blood-brain barrier (BBB), observations towards an increased permeability after exposure to isoflurane are reported. In this study we investigated the effect of a 2-hour isoflurane exposure on apoptosis of the cerebral endothelium following 24 hours of hypoxia in an in vitro BBB model using astrocyte-conditioned human umbilical vein endothelial cells (AC-HUVECs). Apoptosis of AC-HUVECs was investigated using light microscopy of the native culture for morphological changes, Western blot (WB) analysis of Bax and Bcl-2, and a TUNEL assay. Treatment of AC-HUVECs with isoflurane resulted in severe cellular morphological changes and a significant dose-dependent increase in DNA fragmentation, which was observed during the TUNEL assay analysis. WB analysis confirmed increases in pro-apoptotic Bax levels at 4 hours and 24 hours and decreases in anti-apoptotic Bcl-2 in a dose-dependent manner compared with the control group. These negative effects of isoflurane on the BBB after a hypoxic challenge need to be taken into account not only in experimental stroke research, but possibly also in clinical practice. |
| first_indexed | 2024-12-23T20:40:27Z |
| format | Article |
| id | doaj.art-b2e692d2f52b46aca23792f2fc1ac628 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T20:40:27Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b2e692d2f52b46aca23792f2fc1ac6282022-12-21T17:31:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3826010.1371/journal.pone.0038260Isoflurane induces endothelial apoptosis of the post-hypoxic blood-brain barrier in a transdifferentiated human umbilical vein endothelial cell model.Michael S DittmarWalter PetermichlFelix SchlachetzkiBernhard M GrafMichael GruberIsoflurane is a popular volatile anesthetic agent used in humans as well as in experimental animal research. In previous animal studies of the blood-brain barrier (BBB), observations towards an increased permeability after exposure to isoflurane are reported. In this study we investigated the effect of a 2-hour isoflurane exposure on apoptosis of the cerebral endothelium following 24 hours of hypoxia in an in vitro BBB model using astrocyte-conditioned human umbilical vein endothelial cells (AC-HUVECs). Apoptosis of AC-HUVECs was investigated using light microscopy of the native culture for morphological changes, Western blot (WB) analysis of Bax and Bcl-2, and a TUNEL assay. Treatment of AC-HUVECs with isoflurane resulted in severe cellular morphological changes and a significant dose-dependent increase in DNA fragmentation, which was observed during the TUNEL assay analysis. WB analysis confirmed increases in pro-apoptotic Bax levels at 4 hours and 24 hours and decreases in anti-apoptotic Bcl-2 in a dose-dependent manner compared with the control group. These negative effects of isoflurane on the BBB after a hypoxic challenge need to be taken into account not only in experimental stroke research, but possibly also in clinical practice.http://europepmc.org/articles/PMC3377664?pdf=render |
| spellingShingle | Michael S Dittmar Walter Petermichl Felix Schlachetzki Bernhard M Graf Michael Gruber Isoflurane induces endothelial apoptosis of the post-hypoxic blood-brain barrier in a transdifferentiated human umbilical vein endothelial cell model. PLoS ONE |
| title | Isoflurane induces endothelial apoptosis of the post-hypoxic blood-brain barrier in a transdifferentiated human umbilical vein endothelial cell model. |
| title_full | Isoflurane induces endothelial apoptosis of the post-hypoxic blood-brain barrier in a transdifferentiated human umbilical vein endothelial cell model. |
| title_fullStr | Isoflurane induces endothelial apoptosis of the post-hypoxic blood-brain barrier in a transdifferentiated human umbilical vein endothelial cell model. |
| title_full_unstemmed | Isoflurane induces endothelial apoptosis of the post-hypoxic blood-brain barrier in a transdifferentiated human umbilical vein endothelial cell model. |
| title_short | Isoflurane induces endothelial apoptosis of the post-hypoxic blood-brain barrier in a transdifferentiated human umbilical vein endothelial cell model. |
| title_sort | isoflurane induces endothelial apoptosis of the post hypoxic blood brain barrier in a transdifferentiated human umbilical vein endothelial cell model |
| url | http://europepmc.org/articles/PMC3377664?pdf=render |
| work_keys_str_mv | AT michaelsdittmar isofluraneinducesendothelialapoptosisoftheposthypoxicbloodbrainbarrierinatransdifferentiatedhumanumbilicalveinendothelialcellmodel AT walterpetermichl isofluraneinducesendothelialapoptosisoftheposthypoxicbloodbrainbarrierinatransdifferentiatedhumanumbilicalveinendothelialcellmodel AT felixschlachetzki isofluraneinducesendothelialapoptosisoftheposthypoxicbloodbrainbarrierinatransdifferentiatedhumanumbilicalveinendothelialcellmodel AT bernhardmgraf isofluraneinducesendothelialapoptosisoftheposthypoxicbloodbrainbarrierinatransdifferentiatedhumanumbilicalveinendothelialcellmodel AT michaelgruber isofluraneinducesendothelialapoptosisoftheposthypoxicbloodbrainbarrierinatransdifferentiatedhumanumbilicalveinendothelialcellmodel |