Lentivirus-mediated downregulation of α-synuclein reduces neuroinflammation and promotes functional recovery in rats with spinal cord injury

Journal of Neuroinflammation, 2019 · DOI: https://doi.org/10.1186/s12974-019-1658-2 · Published: December 10, 2019

Simple Explanation

This study investigates the role of α-synuclein in neuroinflammation following spinal cord injury (SCI) in rats. The researchers used a lentivirus to reduce α-synuclein expression at the injury site and observed the effects on inflammation and functional recovery. The study found that reducing α-synuclein led to decreased inflammatory infiltration, preserved myelin, and improved motor function recovery in rats with SCI. The results suggest that targeting α-synuclein could be a potential therapeutic strategy to reduce neuroinflammation and promote recovery after spinal cord injury.

Study Duration

28 days

Participants

120 adult male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Downregulation of α-synuclein reduces inflammatory infiltration and preserves myelin after SCI.
2
α-Synuclein knockdown promotes the shift of microglia/macrophages from a pro-inflammatory (M1) to an anti-inflammatory (M2) phenotype.
3
Reducing α-synuclein improves blood-cerebrospinal barrier function and reduces MMP-9 expression.

Research Summary

This study demonstrates that lentivirus-mediated downregulation of α-synuclein reduces neuroinflammation and promotes functional recovery in rats with SCI. The study shows that reducing α-synuclein promotes the conversion of microglia from a pro-inflammatory to an anti-inflammatory phenotype, preventing neuronal loss after SCI. Furthermore, the study indicates that reducing α-synuclein can improve blood-cerebrospinal barrier function and astrocyte activation after SCI, reducing neuroinflammation and conferring a neuroprotective immune microenvironment.

Practical Implications

Therapeutic Target

α-Synuclein may be a potential therapeutic target for reducing neuroinflammation and promoting recovery after spinal cord injury.

Immune Modulation

Modulating microglial polarization by targeting α-synuclein could improve the immune microenvironment in the spinal cord after injury.

Barrier Protection

Reducing α-synuclein may help protect the blood-cerebrospinal barrier, reducing peripheral blood infiltration and inflammation.

Study Limitations

1
Neuroinflammatory changes in the acute phase in the LV-SNCA-shRNA treatment group were unobservable due to in vivo transfection taking 4–5 days.
2
The specific cell markers should be detected in subsequent studies to determine the impact on inflammation after SCI.
3
The exact signalling pathway is not described here, and the relationship between inflammation and synucleinopathies is unclear.

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