Back to Search
Start Over
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 (Cambridge, Mass.) [Mol Med] 2021 Apr 09; Vol. 27 (1), pp. 37. Date of Electronic Publication: 2021 Apr 09. - Publication Year :
- 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.<br />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.<br />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.<br />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 :
- Animals
Brain Injuries genetics
Brain Injuries metabolism
Cerebral Cortex metabolism
Cytokines metabolism
Endopeptidases metabolism
Infarction, Middle Cerebral Artery genetics
Infarction, Middle Cerebral Artery metabolism
Ischemic Stroke genetics
Ischemic Stroke metabolism
NF-KappaB Inhibitor alpha metabolism
Neuroglia metabolism
Neurons metabolism
Neuroprotection
Rats, Sprague-Dawley
Signal Transduction
Transcription Factor RelA metabolism
Rats
Brain Injuries therapy
Electroacupuncture
Endopeptidases genetics
Infarction, Middle Cerebral Artery therapy
Ischemic Stroke therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1528-3658
- Volume :
- 27
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular medicine (Cambridge, Mass.)
- Publication Type :
- Academic Journal
- Accession number :
- 33836646
- Full Text :
- https://doi.org/10.1186/s10020-021-00297-0