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OTULIN is a new target of EA treatment in the alleviation of brain injury and glial cell activation via suppression of the NF-κB signalling pathway in acute ischaemic stroke rats
- Source :
- Molecular Medicine, Vol 27, Iss 1, Pp 1-19 (2021), Molecular Medicine
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Objective Ovarian tumour domain deubiquitinase with linear linkage specificity (OTULIN) is a potent negative regulator of the nuclear factor-κB (NF-κB) signalling pathway, and it plays a strong neuroprotective role following acute ischemic stroke. Electroacupuncture (EA) is an effective adjuvant treatment for reducing brain injury and neuroinflammation via the inhibition of NF-κB p65 nuclear translocation, but the underlying mechanism is not clear. The present study investigated whether OTULIN was necessary for EA to mitigate brain injury and glial cell activation in a transient middle cerebral artery occlusion (tMCAO) model in rats. Methods An acute ischaemic stroke model was established via tMCAO surgery in Sprague–Dawley (SD) rats. EA was performed once daily at “Baihui (GV 20)”, “Hegu (LI 4)”, and “Taichong (LR 3)” acupoints. The effect of EA on the spatiotemporal expression of OTULIN in the ischaemic penumbra of the cerebral cortex was detected within 7 days after reperfusion. The effects of OTULIN gene silencing on EA neurological deficits, cerebral infarct volume, neuronal damage, the activation of microglia and astrocytes, the contents of tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6), and the expression of p-IκBa, IκBa and nucleus/cytoplasm NF-κB p65 protein were assessed. Results EA treatment increased endogenous OTULIN expression, which peaked at 48 h. Enhanced OTULIN was primarily located in neurons, but a small amount of OTULIN was detected in microglia. OTULIN silencing obviously reversed EA neuroprotection, which was demonstrated by worsened neurobehavioural performance, cerebral infarct volume and neuronal injury. The inhibitory effect of EA on the NF-κB pathway was also attenuated by enhanced IκBα phosphorylation and NF-κB p65 nuclear translocation. EA partially inhibited the transformation of microglia and astrocytes from resting states to activated states and reduced the secretion of TNF-α, IL-1β and IL-6. However, these preventive effects were reversed after the silencing of OTULIN expression. Conclusions OTULIN provides a new potential therapeutic target for EA to alleviate acute ischaemic stroke-induced brain injury and the activation of glial cells, which are related to suppression of the NF-κB signalling pathway.
- Subjects :
- OTULIN
Pharmacology
Neuroprotection
Rats, Sprague-Dawley
NF-κB signalling pathway
lcsh:Biochemistry
NF-KappaB Inhibitor alpha
Endopeptidases
Genetics
medicine
Gene silencing
Animals
lcsh:QD415-436
Brain injury
Glial activation
Molecular Biology
Genetics (clinical)
Neuroinflammation
Ischemic Stroke
Cerebral Cortex
Neurons
Microglia
business.industry
lcsh:RM1-950
Transcription Factor RelA
Infarction, Middle Cerebral Artery
Hedgehog signaling pathway
IκBα
medicine.anatomical_structure
Electroacupuncture
lcsh:Therapeutics. Pharmacology
Cerebral cortex
Brain Injuries
Acute ischaemic stroke
Molecular Medicine
Cytokines
Cell activation
business
Neuroglia
Signal Transduction
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 15283658 and 10761551
- Volume :
- 27
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine
- Accession number :
- edsair.doi.dedup.....331fdc6ef941b2a44590ffbe7f3524bf