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Cell Physiol Biochem. 2018;51(3):1448-1460. doi: 10.1159/000495593. Epub 2018 Nov 28.

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.

Author information

1
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang, China.
2
Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, China.
3
Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
4
Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, Chinayu8220182@163.com.
5
Jiangxi Province key of Laboratory of Anesthesiology, Nanchang, China.

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.

KEYWORDS:

Alpha-lipoic acid preconditioning; Cerebral ischaemia/reperfusion injury; Inflammation; Ischaemic postconditioning; TLR4

PMID:
30485844
DOI:
10.1159/000495593
[Indexed for MEDLINE]
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