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Updated: Sep 9, 2025
Acute Brain Trauma in Mice Followed By Longitudinal Two-photon Imaging
Published on: April 6, 2014
Intraoperative application of an antioxidant nanoparticle-hydrogel targeting microglia regulates neuroinflammation in
Yuhan Han1,2, Jiacheng Gu1,2, Miaomiao Xu3
1Brain Injury Center, Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Microglia play a critical role in neuroinflammation, a key secondary injury mechanism following traumatic brain injury (TBI). The colony-stimulating factor 1 receptor (CSF-1R) inhibitor PLX5622 has shown promise in suppressing neuroinflammation by depleting microglia, but it lacks specificity in targeting microglia at the injury site. To overcome this limitation, we developed PLX5622 nanoparticles functionalized with the CAQK peptide for lesion-specific targeting and combined them with a hydrogel (GelMA-PPS) that possesses potent reactive oxygen species (ROS) scavenging capabilities. This nanoparticle-hydrogel drug delivery system (GelMA-PPS/P) significantly enhanced the delivery efficiency and therapeutic efficacy of PLX5622 in TBI treatment. Localized administration of this system effectively depleted microglia at the injury site, suppressed neuroinflammation, and reduced the release of inflammatory cytokines. Its ROS scavenging ability was also validated in vitro and in vivo. Together, these effects synergistically improved neurological function recovery in TBI mouse models. This innovative strategy offers a comprehensive and targeted approach to managing neuroinflammation after TBI, providing a promising avenue for advancing TBI therapies.
Insights
Targeted nanoparticles and hydrogels deliver PLX5622 to deplete microglia and reduce neuroinflammation after traumatic brain injury (TBI), significantly improving neurological recovery.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Drug Delivery Systems
Background:
- Microglia are key drivers of neuroinflammation following traumatic brain injury (TBI).
- Existing treatments like CSF-1R inhibitors lack specificity for targeting microglia at injury sites.
- Reactive oxygen species (ROS) exacerbate TBI-induced damage.
Purpose of the Study:
- To develop a targeted drug delivery system for enhanced TBI treatment.
- To improve the specificity and efficacy of microglia depletion therapy.
- To mitigate neuroinflammation and promote neurological recovery post-TBI.
Main Methods:
- PLX5622 nanoparticles functionalized with CAQK peptide for lesion-specific targeting.
- Combination with a reactive oxygen species (ROS) scavenging hydrogel (GelMA-PPS).
- Localized administration and in vitro/in vivo validation of the nanoparticle-hydrogel system (GelMA-PPS/P).
Main Results:
- The GelMA-PPS/P system demonstrated enhanced delivery and therapeutic efficacy of PLX5622.
- Effective depletion of microglia at the TBI lesion site.
- Suppression of neuroinflammation, reduced inflammatory cytokine release, and validated ROS scavenging.
- Significant improvement in neurological function recovery in TBI mouse models.
Conclusions:
- The developed nanoparticle-hydrogel system offers a targeted and comprehensive approach to TBI management.
- This strategy effectively reduces neuroinflammation and promotes functional recovery.
- This innovative approach holds promise for advancing TBI therapies.
