Neutrophil elastase inhibition effectively rescued angiopoietin-1 decrease and inhibits glial scar after spinal cord...

Area of Science:

• Neuroscience
• Vascular Biology
• Pharmacology

Background:

• Spinal cord injury (SCI) triggers neutrophil elastase (NE) release, compromising vascular integrity.
• Angiopoietins (ANGPTs) are crucial for vascular stabilization, but their role post-SCI is complex.
• NE's impact on ANGPTs and vascular destabilization after SCI requires further elucidation.

Purpose of the Study:

• To investigate the role of neutrophil elastase (NE) in vascular endothelium disruption post-spinal cord injury (SCI).
• To determine the effect of NE on angiopoietin (ANGPT) expression following SCI.
• To evaluate the therapeutic potential of a specific NE inhibitor, sivelestat, in a rat SCI model.

Main Methods:

• Assessed tubule formation and ANGPT expression in endothelial cells exposed to recombinant NE.
• Quantified NE, ANGPT-1, and ANGPT-2 expression at various time points post-SCI in a rat compression model.
• Administered sivelestat sodium post-SCI and evaluated vascular stabilization, inflammatory markers, glial scar formation, locomotor function, and neuropathic pain.

Main Results:

• SCI induced increased NE and ANGPT-2, with decreased ANGPT-1 levels.
• Sivelestat treatment upregulated ANGPT-1 via the AKT pathway, stabilized vasculature, and reduced tight junction protein degradation.
• Sivelestat attenuated inflammation, decreased glial scar formation, promoted blood vessel stabilization, improved hindlimb locomotor function, and reduced neuropathic pain.

Conclusions:

• Neutrophil elastase (NE) inhibition with sivelestat is a promising therapeutic strategy for spinal cord injury (SCI).
• Sivelestat promotes vascular stabilization by upregulating angiopoietin-1 (ANGPT-1) and mitigating secondary damage.
• NE inhibition facilitates functional recovery and reduces neuropathic pain after SCI.