4.3 Article

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

Journal

NEUROMOLECULAR MEDICINE
Volume 23, Issue 2, Pages 267-284

Publisher

HUMANA PRESS INC
DOI: 10.1007/s12017-020-08611-5

Keywords

Gal-9; TLR-4; ICH; Microglia; Neuroinflammation; Neuronal restoration

Categories

Funding

  1. National Key R&D Program of China [2018YFC1312600, 2018YFC1312601]
  2. National Natural Science Foundation of China [81873741]
  3. Suzhou Science and Technology [SS2019056]
  4. Jiangsu Commission of Health [K2019001]
  5. Suzhou Key Medical Centre [Szzx201501]
  6. Scientific Department of Jiangsu Province [BE2017656]

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Intracerebral hemorrhage is a devastating disease with high mortality rates. Galactose lectin-9 (Gal-9) plays a crucial role in immune tolerance and inflammation, and increasing its content in the brain after ICH can reduce cell death and improve motor, sensory, learning, and memory abilities in rats. This suggests that Gal-9 could be a potential target for clinical treatment of ICH.
Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. Galactose lectin-9 (Gal-9) belongs to the family of beta-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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