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Related Experiment Video

Updated: Aug 25, 2025

Author Spotlight: Advancing Traumatic Brain Injury Research - A Closed-Head Model for Accurate Replication and Rapid Assessment
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Dexamethasone-Loaded Hydrogels Improve Motor and Cognitive Functions in a Rat Mild Traumatic Brain Injury Model.

Christian Macks1, Daun Jeong1, Sooneon Bae2

  • 1Drug Design, Development, and Delivery (4D) Laboratory, Department of Bioengineering, Clemson University, Clemson, SC 29615, USA.

International Journal of Molecular Sciences
|October 14, 2022
PubMed
Summary

Hydrogel therapy using dexamethasone-conjugated hyaluronic acid (HA-DXM) significantly improved motor and cognitive functions in rats after traumatic brain injury (TBI). This treatment reduced neuroinflammation, apoptosis, and lesion volume, offering a promising TBI therapeutic approach.

Keywords:
apoptosiscognitive functiondexamethasonehydrogelmotor functionneuroinflammationtraumatic brain injury

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Area of Science:

  • Biomaterials Science
  • Neuroscience
  • Regenerative Medicine

Background:

  • Traumatic brain injury (TBI) recovery is hindered by secondary neuroinflammation.
  • Dexamethasone (DX) can mitigate neuroinflammation by targeting microglia and macrophages.
  • Previous work established PEG-bis-AA/HA-DXM hydrogels for reducing TBI-induced inflammation and improving motor function at 7 days post-injury (DPI).

Purpose of the Study:

  • To evaluate the efficacy of PEG-bis-AA/HA-DXM hydrogels in improving motor and cognitive functions at 14 DPI in a mild-TBI rat model.
  • To assess the impact of these hydrogels on secondary injury markers, including neuroinflammation and apoptosis, at 14 DPI.

Main Methods:

  • Development of hydrolytically degradable poly(ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) hydrogels.
  • Conjugation of dexamethasone (DX) to hyaluronic acid (HA-DXM) for sustained drug delivery.
  • Local application of PEG-bis-AA/HA-DXM hydrogels in a rat mild-controlled cortical impact (CCI) TBI model.
  • Assessment of motor function using the rotarod test and cognitive function via the Morris water maze test at 14 DPI.
  • Histological analysis to evaluate neuroinflammation, apoptosis, and lesion volume at 14 DPI.

Main Results:

  • PEG-bis-AA/HA-DXM treated rats showed significantly improved motor function compared to untreated TBI controls.
  • Cognitive functions were substantially enhanced in the hydrogel-treated group, as evidenced by the Morris water maze test.
  • Reduced inflammatory response, apoptosis, and lesion volume were observed in the PEG-bis-AA/HA-DXM treated group at 14 DPI.

Conclusions:

  • Local application of PEG-bis-AA/HA-DXM hydrogels promotes significant recovery of motor and cognitive functions following mild TBI.
  • The hydrogel treatment effectively mitigates secondary injury processes, including neuroinflammation and apoptosis.
  • PEG-bis-AA/HA-DXM hydrogels represent a promising therapeutic strategy for TBI treatment.