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Protective Effects of Urinary Trypsin Inhibitor on Vascular Permeability Following Subarachnoid Hemorrhage in a Rat Model.
- Source :
- CNS Neuroscience & Therapeutics; Sep2013, Vol. 19 Issue 9, p659-666, 8p
- Publication Year :
- 2013
-
Abstract
- Aims Inflammation and apoptosis play important roles in increasing vascular permeability following subarachnoid hemorrhage (SAH). The objective of this study was to evaluate whether urinary trypsin inhibitor (UTI), a serine protease inhibitor, attenuates vascular permeability by its antiinflammatory and antiapoptotic effects after experimental SAH. Methods Subarachnoid hemorrhage models were established in adult male Sprague-Dawley rats by endovascular perforation. UTI was administered by intraperitoneal injection immediately following SAH. Brain edema was assessed by magnetic resonance imaging (MRI) at 24 h after SAH. Neurological deficits, brain water content, vascular permeability, malondialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity were evaluated. Immunohistochemical staining and Western blot were used to explore the underlying protective mechanism of UTI. Results Urinary trypsin inhibitor 50,000 U/kg significantly attenuated brain edema and neurological deficits and reduced vascular permeability at 24 h after SAH. MDA concentration and MPO activity in hippocampus were significantly decreased with UTI treatment. Furthermore, the levels of phosphorylated JNK, NF-κB (p65), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and proapoptotic protein p53, caspase-3 were elevated in the microvascular endothelial cells of the hippocampus after SAH, which were alleviated with UTI treatment. Conclusion Urinary trypsin inhibitor reduced vascular permeability after SAH through its antiinflammatory and antiapptotic effects via blocking the activity of JNK, NF-κB, and p53. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17555930
- Volume :
- 19
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- CNS Neuroscience & Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 89806250
- Full Text :
- https://doi.org/10.1111/cns.12122