Protective effect of Toll-like receptor-4 inhibitor TAK-242 on hippocampal inflammatory injury in rats with post-stroke depression

  • XIE Yuxin ,
  • ZHANG Kefan ,
  • LI Yufei ,
  • CHANG Xin ,
  • XI Fuqiang
Expand
  • 1. The First Affiliated Hospital of Baotou Medical College, Baotou 014010,China;
    2. Baotou Medical College

Received date: 2024-04-10

  Online published: 2024-12-24

Abstract

Objective: To investigate the protective mechanism of TAK-242 on hippocampal inflammatory injury in rats with post-stroke depression. Methods: A total of 54 male 3-month-old SD rats were divided into sham operation group (n=18), post-stroke depression (PSD) model group (n=18) and TAK group (n=18). The middle cerebral artery occlusion (MCAO) model was established by suture method, and then chronic unpredictable mild stress (CUMS) stimulation was performed for 3 weeks to establish the PSD model. After the PSD model was successfully established, the TAK group was intraperitoneally injected with diluted TAK-242 0.3 mg/kg, which was performed on the 5th, 10th, 15th and 20th day of CUMS, respectively. The level of IL-1β in peripheral blood was detected by enzyme-linked immunosorbent assay. Results: Compared with the sham operation group, the body weight, sucrose preference index and movement (LA) of the PSD group and the TAK group were lower than those of the sham operation group, and the level of IL-1β was significantly increased (P<0.05). Compared with PSD group, the body weight, sucrose preference index and LA of rats in TAK group were increased, and the expression level of IL-1β was decreased (P<0.05). Conclusion: TAK-242 can reduce the expression of IL-1β in peripheral blood by inhibiting TLR4 signaling pathway, thus exerting a neuroprotective effect on hippocampal inflammatory injury in rats with post-stroke depression, and providing new ideas for clinical prevention and treatment of post-stroke depression.

Cite this article

XIE Yuxin , ZHANG Kefan , LI Yufei , CHANG Xin , XI Fuqiang . Protective effect of Toll-like receptor-4 inhibitor TAK-242 on hippocampal inflammatory injury in rats with post-stroke depression[J]. Journal of Baotou Medical College, 2024 , 40(12) : 24 -27 . DOI: 10.16833/j.cnki.jbmc.2024.12.005

References

[1] Blochl M, Meissner S, Nestler S. Does depression after stroke negatively influence physical disability A systematic review and meta-analysis of longitudinal studies[J]. J Affect Disord, 2019,247:45-56.
[2] 王岩,彭颜晖. 卒中后抑郁的发病机制和治疗研究进展[J]. 浙江医学,2023,45(2):220-224.
[3] Luo L, Li C, Du X, et al. Effect of aerobic exercise on BDNF/proBDNF expression in the ischemic hippocampus and depression recovery of rats after stroke[J]. Behav Brain Res,2019,362:323-331.
[4] Amani M, Shokouhi G, Salari A. Minocycline prevents the development of depression-like behavior and hippocampal inflammation in a rat model of Alzheimer's disease[J]. Psychopharmacology, 2019,236(4):1281-1292.
[5] Korostynski M, Holnkis D, Piechota M, et al. Toll-like receptor 4-mediated cytokine synthesis and post-stroke depressive symptoms[J]. Transl Psychiatry, 2021,11(1):246.
[6] Feng Y, Gao JL, Cui Y, et al. Neuroprotective effects of resatorvid against traumatic brain injury in rat: involvement of neuronal autophagy and TLR4 signaling pathway[J]. Cell Mol Neurobiol, 2017,37(1):155-168.
[7] Sheikh AM, Yano S, Mitaki S, et al. A Mesenchymal stem cell line (B10) increases angiogenesis in a rat MCAO model[J]. Exp Neurol, 2019,311:182-193.
[8] Zhang ZB, Tan YX, Zhao Q, et al. miRNA-7a-2-3p inhibits neuronal apoptosis in oxygen-glucose deprivation (OGD) model[J]. Front Neurosci, 2019,13:16.
[9] Willner P, Towell A, Sampson D, et al. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant[J]. Psychopharmacology, 1987,93(3):358-364.
[10] 刘文嵚,陈静,张萌萌,等. NMDA受体3A亚基基因敲除对小鼠焦虑和抑郁样行为的影响[J]. 神经解剖学杂志,2022,38(4):403-410.
[11] Kang HJ, Bae KY, Kim SW, et al. Effects of interleukin-6, interleukin-18, and statin use, evaluated at acute stroke, on post-stroke depression during 1-year follow-up[J]. Psychoneuroendocrinology, 2016,72:156-160.
[12] Pascoe MC, Crewther SG, Carey LM, et al. Homocysteine as a potential biochemical marker for depression in elderly stroke survivors[J]. Food Nutr Res, 2012,56(1):14973
[13] Su Y, Yuki M, Hirayama K. Abstract P294:short-term outcome of post-stroke fatigue during the transition from hospital to home[J]. Stroke, 2021,52:AP294-AP294.
[14] 刘元月,胡丹,丁彩霞,等. 柴胡加龙骨牡蛎汤对卒中后抑郁大鼠小胶质细胞极化及突触可塑性的影响[J]. 南京中医药大学学报,2023,39(8):746-752.
[15] Ghaemi A, Sajadian A, Khodaie B, et al. Immunomodulatory effect of toll-like receptor-3 ligand poly I: C on cortical spreading depression[J]. Mol Neurobiol, 2016,53(1):143-154.
Outlines

/