Point-of-Injury Treatment with Hydrogel Containing Dexamethasone Improves Cognitive Function and Reduces Secondary...

Area of Science:

• Biomaterials Science
• Neuroscience
• Regenerative Medicine

Background:

• Traumatic brain injury (TBI) leads to progressive neurodegeneration and impaired functional recovery.
• Systemic dexamethasone (DX) reduces inflammation but causes adverse effects; local delivery is needed.
• Previous work showed PEG-bis-AA/HA-DXM hydrogels improved motor function at 7 days post-injury (DPI).

Purpose of the Study:

• To evaluate the long-term effects of PEG-bis-AA/HA-DXM hydrogel on cognitive function and secondary injury in a rat TBI model at 14 DPI.
• To assess the potential of localized, sustained DX delivery for TBI treatment.

Main Methods:

• Rats with moderate controlled cortical impact (CCI) TBI received PEG-bis-AA/HA-DXM hydrogel treatment immediately after injury.
• Cognitive function was assessed using the Morris Water Maze test.
• Histological analysis was performed to evaluate lesion volume, neuroinflammation, and apoptosis.

Main Results:

• Hydrogel treatment significantly improved cognitive performance, evidenced by reduced latency and distance to find the target, and increased target crossings.
• Histological analysis revealed reduced lesion volume, decreased inflammatory response, and lower apoptosis in the hydrogel treatment group compared to controls.
• These positive effects were observed at 14 DPI, indicating sustained therapeutic benefits.

Conclusions:

• The PEG-bis-AA/HA-DXM hydrogel effectively improves cognitive function following TBI.
• Local, sustained delivery of dexamethasone via hydrogels reduces secondary injury, including inflammation and apoptosis.
• This localized hydrogel treatment represents a promising therapeutic strategy for enhancing long-term recovery after TBI.