Microenvironment-Responsive Hydrogel Reduces Seizures After Traumatic Brain Injury in Juvenile Rats by Reducing

Zhengzhong Han1,2, Zeqi Zhao2,3, Hao Yu4

  • 1Department of Neurosurgery, Xuzhou Children's Hospital, No. 18 Sudi North Road, Quanshan District, Xuzhou, 221002, P. R. China.

PubMed

Insights

A novel hydrogel delivers berberine (BBR) past the blood-brain barrier to treat traumatic brain injury (TBI). This approach mitigates oxidative stress and neuroinflammation, potentially reducing complications like post-traumatic epilepsy (PTE).

Area of Science:

  • Biomaterials Science
  • Neuroscience
  • Regenerative Medicine

Background:

  • Traumatic brain injury (TBI) is a leading cause of childhood mortality and disability.
  • TBI can lead to severe complications, including post-traumatic epilepsy (PTE), linked to oxidative stress and neuroinflammation.
  • The blood-brain barrier (BBB) limits systemic drug delivery for TBI treatment, hindering early intervention with agents like berberine (BBR).

Purpose of the Study:

  • To develop a microenvironment-responsive hydrogel system for targeted delivery of BBR and poly(propylene sulfide) nanoparticles (PPS60) to the TBI site.
  • To investigate the efficacy of this hydrogel system in mitigating TBI-induced oxidative stress and neuroinflammation.
  • To evaluate the potential of the hydrogel treatment in facilitating functional recovery and reducing seizures post-TBI.

Main Methods:

  • Fabrication of a gelatin methacrylate (GM) hydrogel loaded with BBR and PPS60 (GM/PB).
  • In situ injection of the GM/PB hydrogel directly onto brain tissue, bypassing the BBB.
  • Assessment of the hydrogel's effects on oxidative stress, neuroinflammation, functional recovery, and seizure activity in TBI models.

Main Results:

  • The GM/PB hydrogel successfully delivered BBR and PPS60 to the brain trauma microenvironment.
  • Treatment with GM/PB hydrogel demonstrated mitigation of oxidative stress and neuroinflammatory responses.
  • GM/PB hydrogel administration facilitated functional recovery and reduced seizure incidence in TBI models.

Conclusions:

  • The developed GM/PB hydrogel system offers a promising strategy for overcoming BBB limitations in TBI treatment.
  • Targeted delivery of BBR via the hydrogel effectively regulates neuroinflammation and reduces oxidative stress.
  • This innovative approach holds potential for minimizing TBI complications and improving patient quality of life.

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