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Galectin-9 Promotes Neuronal Restoration via Binding TLR-4 in a Rat Intracerebral Hemorrhage Model

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Abstract

Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. Galactose lectin-9 (Gal-9) belongs to the family of β-galactoside-binding lectins, which has been shown to play a vital role in immune tolerance and inflammation. However, the function of Gal-9 in ICH has not been fully studied in details. Several experiments were carried out to explore the role of Gal-9 in the late period of ICH. Primarily, ICH models were established in male adult Sprague Dawley (SD) rats. Next, the relative protein levels of Gal-9 at different time points after ICH were examined and the result showed that the level of Gal-9 increased and peaked at the 7th day after ICH. Then we found that when the content of Gal-9 increased, both the number of M2-type microglia and the corresponding anti-inflammatory factors also increased. Through co-immunoprecipitation (CO-IP) analysis, it was found that Gal-9 combines with Toll-like receptor-4 (TLR-4) during the period of the recovery after ICH. TUNEL staining and Fluoro-Jade B staining (FJB) proved that the amount of cell death decreased with the increase of Gal-9 content. Additionally, several behavioral experiments also demonstrated that when the level of Gal-9 increased, the motor, sensory, learning, and memory abilities of the rats recovered better compared to the ICH group. In short, this study illustrated that Gal-9 takes a crucial role after ICH. Enhancing Gal-9 could alleviate brain injury and promote the recovery of ICH-induced injury, so that Gal-9 may exploit a new pathway for clinical treatment of ICH.

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Abbreviations

Gal-9:

Galactose lectin-9

ICH:

Intracerebral hemorrhage

TLR-4:

Toll-like receptor-4

TIM-3:

T-cell immunoglobulin and mucin domain 3

SD:

Sprague Dawley

CNS:

Central nervous system

IL-4:

Interleukin-4

IL-13:

Interleukin-13

WB:

Western Blotting

CO-IP:

Co-immunoprecipitation

FJB:

Fluoro-Jade B

CRD:

Carbohydrate recognition domain

DCs:

Dendritic cells

ELISA:

Enzyme-linked immunosorbent assay

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Funding

This work was supported by the National Key R&D Program of China (No. 2018YFC1312600 and 2018YFC1312601), National Natural Science Foundation of China (No. 81873741), Suzhou Science and Technology (No. SS2019056), Jiangsu Commission of Health (No. K2019001), Suzhou Key Medical Centre (No. Szzx201501), and Scientific Department of Jiangsu Province (No. BE2017656).

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    1. Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China

      Tianyu Liang, Cheng Ma, Tianyi Wang, Ruming Deng, Jiasheng Ding, Wenjie Wang, Zhongmou Xu, Xiang Li, Haiying Li, Qing Sun, Haitao Shen, Zhong Wang & Gang Chen

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    1. Tianyu Liang
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    2. Cheng Ma
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    3. Tianyi Wang
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    Liang, T., Ma, C., Wang, T. et al. Galectin-9 Promotes Neuronal Restoration via Binding TLR-4 in a Rat Intracerebral Hemorrhage Model. Neuromol Med 23, 267–284 (2021). https://doi.org/10.1007/s12017-020-08611-5

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