Neuronal Serpina3n is an endogenous protector against blood brain barrier damage following cerebral ischemic stroke.
J Cereb Blood Flow Metab
; 43(2): 241-257, 2023 02.
Article
in En
| MEDLINE
| ID: mdl-36457151
ABSTRACT
Ischemic stroke results in blood-brain barrier (BBB) disruption, during which the reciprocal interaction between ischemic neurons and components of the BBB appears to play a critical role. However, the underlying mechanisms for BBB protection remain largely unknown. In this study, we found that Serpina3n, a serine protease inhibitor, was significantly upregulated in the ischemic brain, predominantly in ischemic neurons from 6 hours to 3 days after stroke. Using neuron-specific adeno-associated virus (AAV), intranasal delivery of recombinant protein, and immune-deficient Rag1-/- mice, we demonstrated that Serpina3n attenuated BBB disruption and immune cell infiltration following stroke by inhibiting the activity of granzyme B (GZMB) and neutrophil elastase (NE) secreted by T cells and neutrophils. Furthermore, we found that intranasal delivery of rSerpina3n significantly attenuated the neurologic deficits after stroke. In conclusion, Serpina3n is a novel ischemic neuron-derived proteinase inhibitor that counterbalances BBB disruption induced by peripheral T cell and neutrophil infiltration after ischemic stroke. These findings reveal a novel endogenous protective mechanism against BBB damage with Serpina3n being a potential therapeutic target in ischemic stroke.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Serpins
/
Brain Ischemia
/
Stroke
/
Ischemic Stroke
Limits:
Animals
Language:
En
Journal:
J Cereb Blood Flow Metab
Year:
2023
Document type:
Article
Affiliation country: