PMID- 25891426
OWN - NLM
STAT- MEDLINE
DCOM- 20160316
LR  - 20181113
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 12
IP  - 2
DP  - 2015 Aug
TI  - Ulinastatin inhibits cerebral ischemia-induced apoptosis in the hippocampus of 
      gerbils.
PG  - 1796-802
LID - 10.3892/mmr.2015.3612 [doi]
AB  - 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 
      step-down avoidance task, following which tissue samples from the gerbils were 
      examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL) staining, western blot analysis for B-cell lymphoma (Bcl-2) and 
      Bcl-2-associated X protein (Bax), immunohistochemistry for caspase-3 and 
      immunofluorescence for 5-bromo-2'-deoxyuridine. The numbers of TUNEL-positive and 
      caspase-3-positive cells in the hippocampal CA1 region increased following 
      cerebral ischemia. The expression of Bax in the hippocampus increased, while the 
      expression of Bcl-2 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 ischemia-induced apoptosis by suppressing apoptosis-associated 
      molecules, and thus ameliorated ischemia-induced short-term 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.
FAU - Cho, Young-Sam
AU  - Cho YS
AD  - Department of Urology, Kangbuk Samsung Hospital, Sungkyunkwan University School 
      of Medicine, Seoul 110‑746, Republic of Korea.
FAU - Shin, Mal-Soon
AU  - Shin MS
AD  - Department of Physiology, Kyung Hee University College of Medicine, Seoul 
      130‑701, Republic of Korea.
FAU - Ko, Il-Gyu
AU  - Ko IG
AD  - Department of Physiology, Kyung Hee University College of Medicine, Seoul 
      130‑701, Republic of Korea.
FAU - Kim, Sung-Eun
AU  - Kim SE
AD  - Department of Physiology, Kyung Hee University College of Medicine, Seoul 
      130‑701, Republic of Korea.
FAU - Kim, Chang-Ju
AU  - Kim CJ
AD  - Department of Physiology, Kyung Hee University College of Medicine, Seoul 
      130‑701, Republic of Korea.
FAU - Sung, Yun-Hee
AU  - Sung YH
AD  - Department of Physical Therapy, Kyungnam University, Changwon 631‑701, Republic 
      of Korea.
FAU - Yoon, Hye-Sun
AU  - Yoon HS
AD  - Department of Pediatrics, Eulji General Hospital, Eulji University School of 
      Medicine, Seoul 139‑872, Republic of Korea.
FAU - Lee, Bong-Jae
AU  - Lee BJ
AD  - Department of Anesthesiology and Pain Medicine, Kang Dong Kyung Hee Hospital, 
      Kyung Hee University College of Medicine, Seoul 134‑727, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150415
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Glycoproteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 3.4.22.- (Caspase 3)
RN  - OR3S9IF86U (urinastatin)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Brain Ischemia/*pathology
MH  - CA1 Region, Hippocampal/*metabolism/pathology
MH  - Caspase 3/genetics/metabolism
MH  - Cell Proliferation/drug effects
MH  - Gerbillinae
MH  - Glycoproteins/*pharmacology
MH  - Immunohistochemistry
MH  - Male
MH  - Microscopy, Fluorescence
MH  - Neuroprotective Agents/*pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - bcl-2-Associated X Protein/genetics/metabolism
PMC - PMC4464423
EDAT- 2015/04/22 06:00
MHDA- 2016/03/17 06:00
PMCR- 2015/04/15
CRDT- 2015/04/21 06:00
PHST- 2013/07/08 00:00 [received]
PHST- 2015/02/03 00:00 [accepted]
PHST- 2015/04/21 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2016/03/17 06:00 [medline]
PHST- 2015/04/15 00:00 [pmc-release]
AID - mmr-12-02-1796 [pii]
AID - 10.3892/mmr.2015.3612 [doi]
PST - ppublish
SO  - Mol Med Rep. 2015 Aug;12(2):1796-802. doi: 10.3892/mmr.2015.3612. Epub 2015 Apr 
      15.