title: Cytoprotective effects of urinary trypsin inhibitor on astrocytes injured by sustained compression.
abstract: Decreased cell membrane integrity is a primary pathological change observed in traumatic brain injury (TBI) that activates a number of complex intercellular and intracellular pathological events, leading to further neural injury. In this paper, we assessed the effects of urinary trypsin inhibitor (UTI) on astrocyte membrane integrity by determining the percentage of lactate dehydrogenase (LDH) released after sustained compression injury using a hydrostatic pressure model of mechanical-like TBI. Astrocytes isolated from SD rat pups were injured by sustained compression. At a pressure of 0.3 MPa for 5 min, a significant increase in LDH release was observed compared with control samples. Astrocytes displayed extensive structural disruption of mitochondrial cristae reflected in their swelling. Based on our initial results, injured astrocytes were treated with UTI at a final concentration of 500, 1,000, 3,000 or 5,000 U/ml for 24 h. The percentage of LDH released from injured astrocytes was significantly decreased when 1,000 and 3,000 U/ml of UTI were used. In a separate experiment, astrocytes were treated with UTI at a final concentration of 1,000 U/ml immediately, or at 30 min, 2, 6, or 24 h after sustained compression. The percentage of LDH release was significantly reduced (P < 0.05) when astrocytes were treated with UTI immediately or 30 min later. Together, our results suggest that UTI may have protective effects on astrocytes injured by sustained compression injury. Furthermore, the early administration (<2 h after injury) of UTI may result in a better outcome compared with delayed administration.
authors.affiliation: SICU, Fujian Provincial Hospital, Fujian Medical University Affiliated Provincial Teaching Hospital, Fuzhou, 350001, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.forename: Rongguo
authors.initials: R
authors.lastname: Yu
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D018929:Cell Culture Techniques; D006023:Glycoproteins / Q000008:administration & dosage*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology
chemical_list: D006023:Glycoproteins; D007770:L-Lactate Dehydrogenase; C028665:urinastatin