Alpha-Lipoic Acid Preconditioning and Ischaemic Postconditioning Synergistically Protect Rats from Cerebral Injury Induced by Ischemia and Reperfusion Partly via Inhibition TLR4/MyD88/ NF-κB Signaling Pathway

Abstract

Background/Aims: A combination of alpha-lipoic acid preconditioning (ALAP) and ischaemic preconditioning (IPC) has not been tested in an in vivo rat cerebral ischaemia/reperfusion injury (I/RI) model, and the potential protective mechanisms have not been well elucidated. The aim of this study was to investigate the role of the TLR4/ MyD88/ NF-κB signaling pathway in the synergistically neuroprotective and anti-inflammatory effects of ALAP and IPC. Methods: One hundred and fifty male Sprague-Dawley rats, weighing 180-230 g, were randomly divided into the following 5 groups: 1) sham-operated control; 2) I/R; 3) I/R+ALAP; 4) I/R+IPC; 5) I/R+IPC+ALAP. After 2 h of reperfusion, the infarct size, neurological deficit scores, brain oedema, oxidative stress, and inflammatory and apoptotic biomarkers were assessed. In addition, reactive oxygen species (ROS) and cell apoptosis were detected by DHE staining and TUNEL staining, respectively. Results: Both ALAP and IPC treatment attenuated the I/RI-induced neuronal injury, reflected by reductions in the infarct size, neurological deficit scores, brain oedema, lactate dehydrogenase (LDH) release and the inflammatory response, as well as decreased HMGB1, TLR4, MyD88, p65, C-Caspase 3 and Bax expression and increased IKB-α, HO-1, SOD-2 and Bcl-2 expression compared to that in the I/R group. Furthermore, the combination of the two strategies had synergistic anti-inflammatory effects and antioxidant benefits, ultimately limiting neuronal apoptosis. Conclusion: The ‘cocktail’ strategy exhibited a significant neuroprotection against I/RI by attenuating neuroinflammation via inhibition of the TLR4/MyD88/NF-κB signaling pathway.

Phenol glycosides extract of Fructus Ligustri Lucidi attenuated depressive‐like behaviors by suppressing neuroinflammation in hypothalamus of mice

“…A new theory supports that hypothalamic-pituitary-adrenal axis (HPA) is activated under psychological stress (Ramirez et al, 2018), and our previous study indicated that IL-1β-induced neuroinflammation in hypothalamus played crucial role in occurrence of depressive-like behaviors in mice after LPS challenge (He et al, 2019). Consistently, this study found that administration with LPS stimulated the increase in content of inflammatory cytokine mature IL-1β in serum and in hypo- (Zhang et al, 2018). This study clearly showed that the activation of TLR-4/MyD88 pathway in hypothalamus of mice with LPS-induced depression was effectively repressed by pre-administration of phenol glycoside extracts.…”

“…The elevated expression of toll‐like receptor‐4 (TLR‐4), a specific receptor to LPS, was associated with physiological stress and contributed to the development of neuropsychiatric diseases like depression (Balan, Beattie, O'Buckley, Aurelian, & Morrow, 2019). LPS‐induced activation of TLR4 signaling includes intracellular signals, like the myeloid differentiation primary response 88 (MyD88)‐dependent pathway that initiates a proinflammatory response stimulating the production of IL‐1β (Zhang et al, 2018). This study clearly showed that the activation of TLR‐4/MyD88 pathway in hypothalamus of mice with LPS‐induced depression was effectively repressed by pre‐administration of phenol glycoside extracts.…”

S100a8 silencing attenuates inflammation, oxidative stress and apoptosis in BV2 cells induced by oxygen‑glucose deprivation and reoxygenation by upregulating GAB1 expression

“…it arises from the temporary interruption of blood supply followed by the recovery of perfusion and concomitant reoxygenation, whereby reperfusion induces neuronal injury in the brain (25). Neuroinflammation and neuronal apoptosis have been reported to be notably increased in the processes of i/r, both of which have been confirmed to play crucial roles in i/r-induced neuronal damage (26) The results of the present study indicated that S100a8 was highly expressed in oGd/r-exposed BV2 cells. Furthermore, S100a8 silencing attenuated oGd/r-induced inflammation, oxidative stress and the apoptosis of BV2 cells by upregulating GaB1 expression.…”

MicroRNA-155 influences cell damage in ischemic stroke via TLR4/MYD88 signaling pathway

“…MyD88 medicating the production and release of inflammatory mediators as a downstream transfection factor of TLR4, is the key substance of inflammatory injury [28]. TLR4/ MyD88 has been verified to be involved in tumor diseases and be bound up with damage of cerebrovascular and brain tissues [29][30][31], and the above experiments also preliminarily confirmed it. Finally, we constructed injured cells with CIS by oxygen and sugar deprivation, and performed CCK-8 and flow cytometry assays.…”