Int Neurourol J.  2016 Dec;20(4):288-295. 10.5213/inj.1632692.346.

Angiopoietin-1 and Angiopoietin-2 Expression Imbalance Influence in Early Period After Subarachnoid Hemorrhage

• Gu H
• Fei ZH
• Wang YQ
• Yang JG
• Zhao CH
• Cai Y
• Zhong XM

• KMID: 2365692
• DOI: http://doi.org/10.5213/inj.1632692.346

Abstract

PURPOSE
Microvascular endothelial integrity is important for maintaining the blood-brain barrier (BBB). However, subarachnoid hemorrhage (SAH) disrupts this integrity, making the BBB dysfunctional"”an important pathophysiological change after SAH. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) regulate microvascular permeability by balancing each other's expression.
METHODS
This study investigated the dynamics of Ang-1 and Ang-2 expression after SAH and the protective effect of Ang-1 on BBB functioning using an endovascular puncture model of rat SAH. The Ang-1 and Ang-2 expression in brain tissue was determined by immunohistochemistry. In addition, Western blotting was used to estimate Ang-1 and Ang-2 concentration and to compare them at 6-72 hours post-SAH cortex and hippocampus. Evans blue viability assay was used to evaluate BBB permeability, and neurological testing was implemented to evaluate neurological impairment during SAH.
RESULTS
It was found that following SAH, Ang-1 expression decreases and Ang-2 expression increases in the cortex, hippocampus, and microvessels. The Ang-1/Ang-2 ratio decreased as quickly as 6 hours after SAH and reached its lowest 1 day after SAH. Finally, it was found that exogenous Ang-1 reduces SAH-associated BBB leakage and improves neurological function in post-SAH rats.
CONCLUSIONS
Our findings suggest that the equilibrium between Ang-1 and Ang-2 is broken in a period shortly after SAH, and the treatment of exogenous Ang-1 injection alleviates neurological dysfunctions through decreasing BBB destruction.

Keyword

Angiopoietin-1; Angiopoietin-2; Subarachnoid Hemorrhage; Blood-Brain Barrier; Brain Injuries

MeSH Terms

Angiopoietin-1*
Angiopoietin-2*
Animals
Blood-Brain Barrier
Blotting, Western
Brain
Brain Injuries
Capillary Permeability
Evans Blue
Hippocampus
Immunohistochemistry
Microvessels
Permeability
Punctures
Rats
Subarachnoid Hemorrhage*
Angiopoietin-1
Angiopoietin-2
Evans Blue