Sub-dose anesthetics combined with chloride regulators protect the brain against chronic ischemia-hypoxia injury
© 2023 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd..
BACKGROUND: Cerebral ischemia-hypoxia leads to excitotoxicity-mediated neuronal damage and cognitive dysfunction, especially in the elderly. Excessive intracellular [Cl- ]i accumulation weakens γ-aminobutyric acid (GABA) compensatory effects. Sub-anesthetic dose of propofol protected the brain against ischemia-hypoxia, which was abolished by blocking Cl- efflux transporter K+ /Cl- cotransporter 2 (KCC2). We aimed to determine whether low-dose anesthetic combined with [Cl- ]i regulators could restore the compensatory GABAergic system and improve cognitive function.
METHODS: Chronic cerebral hypoxia (CCH) model was established by bilateral carotid artery ligation in aged rats. Sub-dose of anesthetics (propofol and sevoflurane) with or without KCC2 agonist N-ethylmaleimide (NEM) or Na+ /K+ /Cl- cotransporter 1 (NKCC1) antagonist bumetanide (BTN) was administered systemically 30 days post-surgery. Primary rat hippocampal neuronal cultures were subjected to hypoxic injury with or without drug treatment. Memory function, hippocampal neuronal survival, GABAergic system functioning, and brain-derived neurotrophic factor (BDNF) expressions were evaluated.
RESULTS: Sub-anesthetic dose of combined propofol (1.2 μg mL-1 ) and sevoflurane [0.7 MAC (minimum alveolar concentration)] did not aggravate the hypoxic brain injury in rats or cell damage in neuronal cultures. Adding either BTN or NEM protected against hypoxic injury, associated with improved cognitive function in vivo, less intracellular accumulation of [Cl- ]i , reduced cell death, restored GABAergic compensation, and increased BDNF expression both in vivo and in vitro.
CONCLUSION: Sub-anesthetic dose of propofol and sevoflurane is a recommended anesthesia regimen in at-risk patients. Restoration of [Cl- ]i homeostasis and GABAergic could further reduce the brain damage caused by ischemia-hypoxia.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
---|---|
Enthalten in: |
CNS neuroscience & therapeutics - 30(2024), 2 vom: 01. Feb., Seite e14379 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Yang, Chenyi [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 01.03.2024 Date Revised 18.04.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1111/cns.14379 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM360446884 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM360446884 | ||
003 | DE-627 | ||
005 | 20240418232250.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1111/cns.14379 |2 doi | |
028 | 5 | 2 | |a pubmed24n1379.xml |
035 | |a (DE-627)NLM360446884 | ||
035 | |a (NLM)37545014 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Yang, Chenyi |e verfasserin |4 aut | |
245 | 1 | 0 | |a Sub-dose anesthetics combined with chloride regulators protect the brain against chronic ischemia-hypoxia injury |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 01.03.2024 | ||
500 | |a Date Revised 18.04.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2023 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd. | ||
520 | |a BACKGROUND: Cerebral ischemia-hypoxia leads to excitotoxicity-mediated neuronal damage and cognitive dysfunction, especially in the elderly. Excessive intracellular [Cl- ]i accumulation weakens γ-aminobutyric acid (GABA) compensatory effects. Sub-anesthetic dose of propofol protected the brain against ischemia-hypoxia, which was abolished by blocking Cl- efflux transporter K+ /Cl- cotransporter 2 (KCC2). We aimed to determine whether low-dose anesthetic combined with [Cl- ]i regulators could restore the compensatory GABAergic system and improve cognitive function | ||
520 | |a METHODS: Chronic cerebral hypoxia (CCH) model was established by bilateral carotid artery ligation in aged rats. Sub-dose of anesthetics (propofol and sevoflurane) with or without KCC2 agonist N-ethylmaleimide (NEM) or Na+ /K+ /Cl- cotransporter 1 (NKCC1) antagonist bumetanide (BTN) was administered systemically 30 days post-surgery. Primary rat hippocampal neuronal cultures were subjected to hypoxic injury with or without drug treatment. Memory function, hippocampal neuronal survival, GABAergic system functioning, and brain-derived neurotrophic factor (BDNF) expressions were evaluated | ||
520 | |a RESULTS: Sub-anesthetic dose of combined propofol (1.2 μg mL-1 ) and sevoflurane [0.7 MAC (minimum alveolar concentration)] did not aggravate the hypoxic brain injury in rats or cell damage in neuronal cultures. Adding either BTN or NEM protected against hypoxic injury, associated with improved cognitive function in vivo, less intracellular accumulation of [Cl- ]i , reduced cell death, restored GABAergic compensation, and increased BDNF expression both in vivo and in vitro | ||
520 | |a CONCLUSION: Sub-anesthetic dose of propofol and sevoflurane is a recommended anesthesia regimen in at-risk patients. Restoration of [Cl- ]i homeostasis and GABAergic could further reduce the brain damage caused by ischemia-hypoxia | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a chloride ion | |
650 | 4 | |a cognitive function | |
650 | 4 | |a hypoxia | |
650 | 4 | |a ischemia | |
650 | 4 | |a propofol | |
650 | 4 | |a sevoflurane | |
650 | 4 | |a γ-Aminobutyric acid | |
650 | 7 | |a Propofol |2 NLM | |
650 | 7 | |a YI7VU623SF |2 NLM | |
650 | 7 | |a Chlorides |2 NLM | |
650 | 7 | |a Brain-Derived Neurotrophic Factor |2 NLM | |
650 | 7 | |a Sevoflurane |2 NLM | |
650 | 7 | |a 38LVP0K73A |2 NLM | |
650 | 7 | |a Anesthetics |2 NLM | |
650 | 7 | |a Bumetanide |2 NLM | |
650 | 7 | |a 0Y2S3XUQ5H |2 NLM | |
650 | 7 | |a K Cl- Cotransporters |2 NLM | |
700 | 1 | |a Wang, Ye |e verfasserin |4 aut | |
700 | 1 | |a Li, Yun |e verfasserin |4 aut | |
700 | 1 | |a Wang, Xinyi |e verfasserin |4 aut | |
700 | 1 | |a Hua, Wei |e verfasserin |4 aut | |
700 | 1 | |a Yang, Zhuo |e verfasserin |4 aut | |
700 | 1 | |a Wang, Haiyun |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t CNS neuroscience & therapeutics |d 2008 |g 30(2024), 2 vom: 01. Feb., Seite e14379 |w (DE-627)NLM17958930X |x 1755-5949 |7 nnns |
773 | 1 | 8 | |g volume:30 |g year:2024 |g number:2 |g day:01 |g month:02 |g pages:e14379 |
856 | 4 | 0 | |u http://dx.doi.org/10.1111/cns.14379 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 30 |j 2024 |e 2 |b 01 |c 02 |h e14379 |