Ulinastatin alleviates traumatic brain injury by reducing endothelin-1

• Published in: Translational neuroscience Vol. 12; no. 1; pp. 001 - 008
• Main Authors: Liu, Ting, Liao, Xing-Zhi, Zhou, Mai-Tao
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 01.01.2021; De Gruyter Poland
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; astrocyte; Astrocytes; Attenuation; Blood-brain barrier; brain edema; Edema; Endothelin 1; Extravasation; Gelatinase B; Glial fibrillary acidic protein; Growth factors; Head injuries; Immunohistochemistry; Inflammation; Injury prevention; Matrix metalloproteinase; Matrix metalloproteinases; Membrane permeability; Metalloproteinase; Moisture content; Neurosurgery; Protease inhibitors; Proteinase inhibitors; Traumatic brain injury; ulinastatin; Vascular endothelial growth factor; Water content; ulinastatin; traumatic brain injury; brain edema; endothelin-1; astrocyte
• ISSN: 2081-3856; 2081-6936; 2081-6936
• DOI: 10.1515/tnsci-2021-0001

Brain edema is one of the major causes of fatality and disability associated with injury and neurosurgical procedures. The goal of this study was to evaluate the effect of ulinastatin (UTI), a protease inhibitor, on astrocytes in a rat model of traumatic brain injury (TBI). A rat model of TBI was established. Animals were randomly divided into 2 groups - one group was treated with normal saline and the second group was treated with UTI (50,000 U/kg). The brain water content and permeability of the blood-brain barrier were assessed in the two groups along with a sham group (no TBI). Expression of the glial fibrillary acidic protein, endthelin-1 (ET-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry and western blot. Effect of UTI on ERK and PI3K/AKT signaling pathways was measured by western blot. UTI significantly decreased the brain water content and extravasation of the Evans blue dye. This attenuation was associated with decreased activation of the astrocytes and ET-1. UTI treatment decreased ERK and Akt activation and inhibited the expression of pro-inflammatory VEGF and MMP-9. UTI can alleviate brain edema resulting from TBI by inhibiting astrocyte activation and ET-1 production.