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Ulinastatin inhibits cerebral ischemia-induced apoptosis in the hippocampus of gerbils

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Ulinastatin is a urinary trypsin inhibitor, originally extracted and purified from human urine. Ulinastatin has cytoprotective effects against ischemic injury in several organs. In the present study, the neuroprotective effects of ulinastatin following ischemic cerebral injury in the hippocampus of gerbils was investigated. To induce transient global ischemia in gerbils, the common carotid arteries were occluded using aneurysm clips for 5 min, and the clips were then removed. Ulinastatin was subcutaneously injected into the gerbils once a day for 7 days at doses of 50,000 or 100,000 U/kg. The gerbils were confronted with a stepdown avoidance task, following which tissue samples from the gerbils were examined using terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) staining, western blot analysis for Bcell lymphoma (Bcl2) and Bcl2associated X protein (Bax), immunohistochemistry for caspase3 and immunofluorescence for 5bromo2'deoxyuridine. The numbers of TUNELpositive and caspase3positive cells in the hippocampal CA1 region increased following cerebral ischemia. The expression of Bax in the hippocampus increased, while the expression of Bcl2 in the hippocampus decreased following cerebral ischemia. These results confirmed that apoptosis in the hippocampus was enhanced following cerebral ischemia in gerbils. The levels of cell proliferation in the hippocampal dentate gyrus were also enhanced by ischemia, which is possibly an adaptive mechanism to compensate for excessive levels of apoptosis. Ulinastatin treatment inhibited ischemiainduced apoptosis by suppressing apoptosisassociated molecules, and thus ameliorated ischemiainduced shortterm memory impairment. The cell proliferation in the hippocampus was also suppressed following ulinastatin treatment. These results suggested the use of ulinastatin as a therapeutic agent for patients with cerebral stroke.
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Document Type: Research Article

Affiliations: 1: Department of Urology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110746, Republic of Korea 2: Department of Physiology, Kyung Hee University College of Medicine, Seoul 130701, Republic of Korea 3: Department of Physical Therapy, Kyungnam University, Changwon 631701, Republic of Korea 4: Department of Pediatrics, Eulji General Hospital, Eulji University School of Medicine, Seoul 139872, Republic of Korea 5: Department of Anesthesiology and Pain Medicine, Kang Dong Kyung Hee Hospital, Kyung Hee University College of Medicine, Seoul 134727, Republic of Korea

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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