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

被引：28

作者：

Lee, S. -R. ^{[1
,2
,3
]}

Lok, J. ^{[1
,2
]}

Rosell, A. ^{[1
,2
,4
]}

Kim, H. -Y. ^{[1
,2
]}

Murata, Y. ^{[1
,2
]}

Atochin, D. ^{[5
]}

Huang, P. L. ^{[5
]}

Wang, X. ^{[1
,2
]}

Ayata, C. ^{[6
]}

Moskowitz, M. A. ^{[6
]}

Lo, E. H. ^{[1
,2
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Neuroprotect Res Lab, Boston, MA 02129 USA

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neuroprotect Res Lab, Boston, MA 02129 USA

[3] Keimyung Univ, Sch Med, Dept Pharmacol, Taegu, South Korea

[4] Massachusetts Gen Hosp, Div Pediat Critical Care Med, Boston, MA 02129 USA

[5] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA

[6] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Ctr, Boston, MA 02129 USA

来源：

NEUROSCIENCE | 2007年 / 150卷 / 01期

关键词：

excitotoxicity; anolkis; neuron; caspase; matrix metalloproteinase;

D O I：

10.1016/j.neuroscience.2007.06.029

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 wildtype 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. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：50 / 57

页数：8

共 36 条

[1] Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia [J].