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Reduction of hippocampal cell death and proteolytic responses in tissue plasminogen activator knockout mice after transient global cerebral ischemia

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Author(s)
S.-R. LEEJ. LOKA. ROSELLH.-Y. KIMY. MURATAD. ATOCHINP. L. HUANGX. WANGC. AYATAM. A. MOSKOWITZE. H. LO
Keimyung Author(s)
Lee, Seong Ryong
Department
Dept. of Pharmacology (약리학)
Journal Title
Neuroscience
Issued Date
2007
Volume
150
Issue
1
Keyword
excitotoxicityanoikisneuroncaspasematrix metalloproteinase
Abstract
Knockout mice deficient in tissue plasminogen activator (tPA) are protected against hippocampal excitotoxicity. But it is unknown whether similar neuroprotection occurs after transient global cerebral ischemia, which is known to selectively affect the hippocampus. In this study, we tested the hypothesis that hippocampal cell death in tPA knockout mice would be reduced after transient global cerebral ischemia, and this neuroprotection would occur concomitantly with amelioration of both intra- and extracellular proteolytic cascades. Wild-type and tPA knockout mice were subjected to 20 min of transient bilateral occlusions of the common carotid arteries. Three days later, Nissl and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining demonstrated that hippocampal cell death was significantly reduced in tPA knockout brains compared with wild-type brains. Caspase-3 and the two major brain gelatinases (matrix metalloproteinase (MMP)-9 and MMP-2) were assessed as representative measurements of intra- and extracellular proteolysis. Post-ischemic levels of caspase-3, MMP-9 and MMP-2 were similarly reduced in tPA knockouts compared with wild-type hippocampi. Taken together, these data suggest that endogenous tPA contributes to hippocampal injury after cerebral ischemia, and these pathophysiologic pathways may involve links to aberrant activation of caspases and MMPs.

Key words
excitotoxicity;
anoikis;
neuron;
caspase;
matrix metalloproteinase
Keimyung Author(s)(Kor)
이성용
Publisher
School of Medicine
Citation
S.-R. LEE et al. (2007). Reduction of hippocampal cell death and proteolytic responses in tissue plasminogen activator knockout mice after transient global cerebral ischemia. Neuroscience, 150(1), 50–57. doi: 10.1016/j.neuroscience.2007.06.029
Type
Article
ISSN
0306-4522
DOI
10.1016/j.neuroscience.2007.06.029
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33540
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pharmacology (약리학)
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