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A Novel In Vitro Model of Blast Traumatic Brain Injury
Published on: December 21, 2018
Injectable reactive oxygen and nitrogen species-scavenging hydrogels for repairing traumatic brain injury
Luzhong Zhang1,2, Wenhui Li2, Jie Cao2
1Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, PR China.
Abstract:
Clinical therapies for traumatic brain injury included pharmacological interventions and surgical procedures; however, the efficacy of these approaches remains unsatisfactory. Traumatic brain injury was commonly accompanied by excessive reactive oxygen species (ROS) and nitrogen species (RNS). The overexpressed ROS/RNS generally led to secondary brain injury. To address these issues, we synthesized the injectable poly (ethylene glycol) diacrylate (PEGDA)/cystamine/agmatine (PCA) hydrogels through Michael addition for repairing traumatic brain injury. Injectable PCA hydrogels could not only fill the brain trauma cavities, but also alleviate the secondary damage to the brain by reducing ROS and RNS. The disulfide bonds of cystamine and agmatine in the hydrogels could separately scavenge ROS and inhibit the activity of nitric oxide synthase. Consequently, injectable hydrogels were locally administrated to the injured brain. Therapeutically, PCA hydrogels significantly enhanced the motor functional recovery, improved the learning ability and memory retention, preserved the survival of neurons, and reduced the activation of glial cells and pro-inflammatory macrophages. The injectable hydrogels offered a potential therapeutic strategy for traumatic brain injury and other neurological diseases.
Insights
New injectable hydrogels effectively treat traumatic brain injury by reducing harmful reactive oxygen species (ROS) and nitrogen species (RNS), improving brain function and neuron survival.
Area of Science:
- Biomaterials Science
- Neuroscience
- Regenerative Medicine
Background:
- Current traumatic brain injury (TBI) treatments lack efficacy.
- TBI is often complicated by excessive reactive oxygen species (ROS) and reactive nitrogen species (RNS), leading to secondary brain damage.
- Developing novel therapeutic strategies to mitigate secondary injury is crucial.
Purpose of the Study:
- To synthesize and evaluate injectable poly (ethylene glycol) diacrylate (PEGDA)/cystamine/agmatine (PCA) hydrogels for TBI repair.
- To assess the capacity of PCA hydrogels to scavenge ROS and RNS and alleviate secondary brain injury.
- To investigate the therapeutic effects of PCA hydrogels on motor function, cognitive abilities, neuronal survival, and neuroinflammation in TBI models.
Main Methods:
- Injectable PCA hydrogels were synthesized using Michael addition.
- The hydrogels' ability to scavenge ROS and inhibit nitric oxide synthase was investigated.
- PCA hydrogels were locally administered to injured brains in a TBI model.
- Therapeutic efficacy was evaluated by assessing motor function, learning and memory, neuronal survival, and glial cell activation.
Main Results:
- PCA hydrogels effectively filled brain trauma cavities and reduced ROS and RNS levels.
- The hydrogels demonstrated significant enhancement in motor functional recovery.
- PCA hydrogels improved learning and memory retention, preserved neuronal survival, and reduced glial cell activation and pro-inflammatory macrophage response.
Conclusions:
- Injectable PCA hydrogels represent a promising therapeutic strategy for traumatic brain injury.
- The hydrogels alleviate secondary brain damage by scavenging ROS and RNS.
- This approach holds potential for treating TBI and other neurological disorders.
