4,4'-Dimethoxychalcone Mitigates Neuroinflammation Following Traumatic Brain Injury Through Modulation of the...

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Traumatic brain injury (TBI) lacks effective clinical treatments.
• Neuroinflammation and neuronal damage are key pathological features of TBI.
• 4,4'-dimethoxychalcone (DMC) is under investigation for TBI therapeutic potential.

Purpose of the Study:

• To investigate the mechanisms of DMC in alleviating neuroinflammation and neuronal damage post-TBI.
• To provide a theoretical basis for developing pharmacological therapies for TBI.
• To explore DMC's effects on neuromotor function, cerebral edema, and molecular pathways.

Main Methods:

• Established a moderate TBI model using fluid percussion injury (FPI).
• Assessed neuromotor function via modified neurological severity score (mNSS) and Morris water maze.
• Quantified gene/protein expression using qRT-PCR, Western blotting, ELISA, and imaging techniques.
• Employed network pharmacology, gene ontology (GO), and KEGG pathway analysis.

Main Results:

• DMC treatment significantly improved neuromotor deficits and reduced cerebral edema in TBI mice.
• DMC suppressed microglial activation and decreased inflammatory factor production in vitro and in vivo.
• DMC reduced neuronal lesions and decreased elevated TREM2 expression post-TBI.
• Network pharmacology predicted the PI3K/AKT signaling cascade as a key pathway.

Conclusions:

• DMC exhibits significant anti-inflammatory and neuroprotective properties for TBI.
• The therapeutic effects of DMC are likely mediated by the TREM2/PI3K/AKT/NF-κB signaling cascade.
• DMC represents a potential therapeutic agent for TBI treatment.