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Traumatic brain injury (TBI) is one of the leading causes of disability and death worldwide, and its pathological process involves persistent neuroinflammation and neuronal death. Pyroptosis, a type of programmed cell death (PCD) triggered by inflammatory signals, plays an important role after TBI. Inhibiting neuroinflammation and pyroptosis is a potential treatment for TBI. Exogenous hydrogen sulfide (H2S) has been shown to have a neuroprotective effect after TBI.
Researchers have developed a surface-filled H2S-releasing silk fibroin hydrogel (H2S@SF hydrogel), which can slowly release H2S and reshape the homeostasis of endogenous H2S in injured neurons. The effect of H2S@SF hydrogel on TBI-induced pyroptosis was studied in a mouse mild TBI model established by controlled cortical impact (CCI).
Microstructure: FESEM observation showed that H2S@SF hydrogel has open and interconnected porous morphological characteristics.
H2S release kinetics: The release rate of H2S in H2S@SF hydrogel was slow, and 90% was released within 24 hours, indicating that a silk protein hydrogel that can slowly release H2S was successfully constructed.
Effects of H2S@SF hydrogel on TBI
Inhibition of pyroptosis and inflammation: H2S@SF hydrogel significantly inhibited the expression of GSDMD, Caspase-1, ASC and NLRP3 in the injured cortex and hippocampus, and reduced the expression of H2S production-related proteins.
Relieve neurodegeneration and brain edema: Nissl and FB staining results showed that H2S@SF hydrogel treatment significantly improved the contraction and dark staining morphology of Nissl bodies and reduced brain edema in the acute phase of brain injury.
Improve motor dysfunction, anxiety behavior and memory deficits: H2S@SF hydrogel treatment promoted the recovery of motor dysfunction, effectively alleviated the anxiety-like behavior of mice caused by brain trauma, and promoted the long-term recovery of neurological function.
Reduce tissue loss and neuroinflammation: H2S@SF hydrogel treatment reduced tissue loss and neuroinflammation caused by TBI and alleviated neuroinflammation.
A coaxial electrospinning GelMA/PLGA-LysoGM1 neural repair scaffold was proposed to promote rapid adhesion, proliferation and functional expression of neuronal cells, while giving cells in situ and long-term drug stimulation to achieve effective protection of damaged neuronal cells and promote their functional recovery
As a new treatment method, H2S@SF hydrogel can inhibit neuronal pyroptosis after brain injury, reduce neurodegeneration and brain edema, promote neurological function recovery, reduce tissue loss and chronic neuroinflammation, and play a neuroprotective role. This study provides a new theoretical basis for the treatment of H2S after brain injury and the clinical application of H2S@SF hydrogel.
Electrospinning Nanofibers Article Source:
https://doi.org/10.1016/j.actbio.2022.11.021
