In:
Frontiers in Neuroscience, Frontiers Media SA, Vol. 15 ( 2021-2-9)
Abstract:
Inflammatory response contributes to brain injury after ischemia and reperfusion (I/R). Our previous literature has shown isoquercetin plays an important role in protecting against cerebral I/R injury. The present study was conducted to further investigate the effect of isoquercetin on inflammation-induced neuronal injury in I/R rats with the involvement of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and inhibitor of NF-κB (I-κB)/nuclear factor-kappa B (NF-κB) signaling pathway mediated by Toll-like receptor 4 (TLR4) and C5a receptor 1 (C5aR1). In vivo middle cerebral artery occlusion and reperfusion (MCAO/R) rat model and in vitro oxygen-glucose deprivation and reperfusion (OGD/R) neuron model were used. MCAO/R induced neurological deficits, cell apoptosis, and release of cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in ischemic brain in rats. Simultaneously, the expression of TLR4 and C5aR1 was significantly up-regulated in both MCAO/R rats and OGD/R neurons, accompanied with the inhibition of cAMP/PKA signaling and activation of I-κB/NF-κB signaling in the cortex of MCAO/R rats. Over-expression of C5aR1 in neurons induced decrease of cell viability, exerting similar effects with OGD/R injury. Isoquercetin acted as a neuroprotective agent against I/R brain injury to suppress inflammatory response and improve cell recovery by inhibiting TLR4 and C5aR1 expression, promoting cAMP/PKA activation, and inhibiting I-κB/NF-κB activation and Caspase 3 expression. TLR4 and C5aR1 contributed to inflammation and apoptosis via activating cAMP/PKA/I-κB/NF-κB signaling during cerebral I/R, suggesting that this signaling pathway may be a potent therapeutic target in ischemic stroke. Isoquercetin was identified as a neuroprotective agent, which maybe a promising therapeutic agent used for the treatment of ischemic stroke and related diseases.
Type of Medium:
Online Resource
ISSN:
1662-453X
DOI:
10.3389/fnins.2021.555543
DOI:
10.3389/fnins.2021.555543.s001
DOI:
10.3389/fnins.2021.555543.s002
DOI:
10.3389/fnins.2021.555543.s003
DOI:
10.3389/fnins.2021.555543.s004
DOI:
10.3389/fnins.2021.555543.s005
DOI:
10.3389/fnins.2021.555543.s006
DOI:
10.3389/fnins.2021.555543.s007
DOI:
10.3389/fnins.2021.555543.s008
DOI:
10.3389/fnins.2021.555543.s009
DOI:
10.3389/fnins.2021.555543.s010
DOI:
10.3389/fnins.2021.555543.s011
DOI:
10.3389/fnins.2021.555543.s012
DOI:
10.3389/fnins.2021.555543.s013
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2411902-7
Permalink