Subanesthetic isoflurane abates ROS-activated MAPK/NF-κB signaling to repress ischemia-induced microglia inflammation and brain injury.

Abstract

Isoflurane (ISO) elicits protective effects on ischemia-induced brain injury. We investigated whether sub-anesthetic (0.7%) ISO post-conditioning attenuates the inflammation and apoptosis in oxygen-glucose deprivation (OGD)-insulted co-cultures (microglia and neurons) in vitro and the brain injury of the middle cerebral arterial occlusion (MCAO) rat. We demonstrated that ISO augmented the viability of OGD-treated microglia and neurons. ISO reduced the expression and activation of COX2 and iNOS in OGD-challenged microglia. ISO repressed the production of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, and monocyte chemoattractant protein-1 in OGD-exposed microglia. ISO also decreased nucleosomal fragmentation and caspase-3 activity but increased mitochondrial membrane potential in OGD-stimulated microglia and neurons. Mechanistically, ISO suppressed OGD-induced microglial inflammation by blocking ROS-regulated p38 MAPK/NF-κB signaling pathway and hampered OGD-triggered microglial apoptosis in a ROS- or NO-dependent fashion. In vivo results with MCAO rats were partly consistent with the in vitro observation. These findings indicate that sub-anesthetic ISO post-conditioning abates the inflammation and apoptosis in OGD-stimulated rat microglia and the apoptosis of OGD-exposed neurons and the brain injuries of MCAO rats, suggesting it as a potentially effective therapeutic approach for ischemic brain damages.

• Authors: Zhiqiang Yao, Ningning Liu, Xiaoshan Zhu, Ling Wang, Yali Zhao, Qinqin Liu, Chunfang Gao, Juntang Li
• Journal: Aging (Aging (Albany NY)) Vol. 12 Issue 24 Pg. 26121-26139 (12 28 2020) ISSN: 1945-4589 [Electronic] United States
• PMID: 33373319 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Inhalation
• Ccl2 protein, rat
• Chemokine CCL2
• IL1B protein, rat
• Il6 protein, rat
• Interleukin-1beta
• Interleukin-6
• Interleukin-8
• NF-kappa B
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• Isoflurane
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Cyclooxygenase 2
• Ptgs2 protein, rat
• p38 Mitogen-Activated Protein Kinases

Topics

• Anesthetics, Inhalation (pharmacology)
• Animals
• Apoptosis (drug effects)
• Brain Ischemia (metabolism)
• Chemokine CCL2 (drug effects, metabolism)
• Coculture Techniques
• Cyclooxygenase 2 (drug effects, metabolism)
• Disease Models, Animal
• Infarction, Middle Cerebral Artery
• Inflammation (metabolism)
• Interleukin-1beta (drug effects, metabolism)
• Interleukin-6 (metabolism)
• Interleukin-8 (drug effects, metabolism)
• Isoflurane (pharmacology)
• Microglia (drug effects, metabolism)
• NF-kappa B (drug effects, metabolism)
• Neurons (drug effects, metabolism)
• Nitric Oxide Synthase Type II
• Rats
• Reactive Oxygen Species (metabolism)
• Tumor Necrosis Factor-alpha (drug effects, metabolism)
• p38 Mitogen-Activated Protein Kinases (drug effects, metabolism)