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

Neuromolecular Med. 2021 Jun;23(2):267-284. doi: 10.1007/s12017-020-08611-5. Epub 2020 Aug 31.

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.

Keywords: Gal-9; ICH; Microglia; Neuroinflammation; Neuronal restoration; TLR-4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Astrocytes / metabolism
  • Basal Ganglia / physiopathology
  • Cerebral Hemorrhage / physiopathology*
  • Disease Models, Animal
  • Male
  • Microglia / metabolism
  • Morris Water Maze Test
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurons / metabolism*
  • Neurons / pathology
  • Organic Anion Transporters / biosynthesis
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / physiology*
  • Protein Binding
  • Protein Interaction Mapping
  • Psychomotor Performance
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / metabolism
  • Recovery of Function
  • Rotarod Performance Test
  • Signal Transduction
  • Single-Blind Method
  • Time Factors
  • Toll-Like Receptor 4 / physiology*

Substances

  • Lgals9 protein, rat
  • Nerve Tissue Proteins
  • Organic Anion Transporters
  • RNA, Small Interfering
  • Recombinant Proteins
  • Tlr4 protein, rat
  • Toll-Like Receptor 4