Low-Intensity Pulsed Ultrasound Attenuates Neuroinflammation and Preserves Synaptic Integrity by Modulating...

Area of Science:

• Neuroscience
• Immunology
• Biomedical Engineering

Background:

• Traumatic brain injury (TBI) causes neuroinflammation, driven by microglia shifting to a proinflammatory M1 phenotype, worsening outcomes.
• Microglial dysfunction after TBI contributes to secondary damage and long-term neurological deficits.

Purpose of the Study:

• To investigate the therapeutic potential of low-intensity pulsed ultrasound (LIPUS) in modulating microglial activation and polarization post-TBI.
• To assess LIPUS effects on neuroinflammation, synaptic integrity, and functional recovery in a mouse model of TBI.

Main Methods:

• Utilized in vitro BV2 and primary microglia models to examine LIPUS effects on interferon-gamma (IFN-γ)-induced microglial activation.
• Employed a controlled cortical impact mouse model to evaluate LIPUS treatment's impact on neuroinflammation, microglial polarization (M1/M2 markers), synaptic integrity, and neurological/cognitive function.
• Investigated LIPUS effects on key inflammatory signaling pathways, including MAPK-NF-κB.

Main Results:

• LIPUS significantly reduced microglial activation and neuroinflammation in TBI mice.
• LIPUS treatment shifted microglial polarization from M1 (CD16) to M2 (CD206), suppressed proinflammatory cytokine release, and inhibited the MAPK-NF-κB pathway in vitro.
• Preserved hippocampal synaptic integrity and improved long-term neurological and cognitive outcomes in TBI mice, even when administered up to 6 hours post-injury.

Conclusions:

• LIPUS promotes a reparative microglial phenotype (M2), mitigating TBI-induced neuroinflammation.
• LIPUS treatment maintains synaptic and neuronal function, facilitating recovery after TBI.
• LIPUS represents a potential noninvasive therapeutic strategy for TBI with translational relevance.