Deficiency of the microglial Hv1 proton channel attenuates neuronal pyroptosis and inhibits inflammatory reaction after spinal cord injury

Journal of Neuroinflammation, 2020 · DOI: https://doi.org/10.1186/s12974-020-01942-x · Published: August 25, 2020

Simple Explanation

Spinal cord injuries (SCI) can lead to significant neurological problems. This study looked at how a specific protein channel, Hv1, found in microglia (a type of immune cell in the brain and spinal cord), affects nerve cell death and inflammation following SCI. The researchers found that when Hv1 is removed from microglia in mice with SCI, there was less nerve cell death (specifically pyroptosis and apoptosis) and reduced inflammation. This suggests that Hv1 plays a role in these harmful processes after SCI. The study also showed that Hv1 influences the production of reactive oxygen species (ROS), which are linked to inflammation and cell damage. By reducing Hv1 activity, the generation of ROS was decreased, leading to improved outcomes after SCI.

Study Duration

28 days

Participants

C57BL/6 female mice (wild-type, WT) and Hv1−/−mice

Evidence Level

Not specified

Key Findings

1
Neuronal apoptosis peaked earlier than pyroptosis after SCI, but pyroptosis lasted longer.
2
Hv1 deficiency reduced neuronal apoptosis and NLRP3-inflammasome-mediated pyroptosis after SCI.
3
Hv1 deficiency downregulated microglial ROS generation after SCI.

Research Summary

Following SCI, neuronal pyroptosis lasted longer and occurred farther away from the injury core compared with that of neuronal apoptosis. Microglial Hv1 deficiency downregulated microglial ROS generation and reduced apoptosis and NLRP3-induced neuronal pyroptosis. Our findings may provide novel insights into Hv1-associated mechanisms underlying neuronal damage after SCI.

Practical Implications

Therapeutic Target

Targeting microglial Hv1 may be a promising therapeutic strategy for reducing neuronal damage and inflammation following spinal cord injury.

Neuroprotection

Inhibiting microglial Hv1 can promote myelin/axonal regeneration and concomitantly improve motor function after SCI.

ROS Reduction

Therapeutic interventions designed to inhibit microglial Hv1 after SCI may be beneficial in afflicted patients by reducing ROS production.

Study Limitations

1
The study used a mouse model, and results may not directly translate to humans.
2
The specific mechanisms by which Hv1 regulates ROS production and NLRP3 inflammasome activation require further investigation.
3
The long-term effects of Hv1 deficiency on spinal cord repair and functional recovery were not fully explored.

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