The Kringle-2 domain of tissue plasminogen activator significantly reduces mortality and brain infarction in middle cerebral artery occlusion rats

被引：3

作者：

Zhang, Haitao ^{[1
,2
]}

Bi, Feng ^{[3
,4
]}

Xiao, Chunlan ^{[1
,2
]}

Liu, Jianxia ^{[4
]}

Wang, Zhixia ^{[4
]}

Liu, Jian-Ning ^{[1
,2
,3
]}

Zhang, Jing ^{[1
,2
,3
]}

机构：

[1] Nanjing Univ, Inst Mol Med, Nanjing 210093, Peoples R China

[2] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China

[3] E China Normal Univ, Inst Mol & Expt Therapeut, Shanghai 200062, Peoples R China

[4] Landing Biopharmaceut Inc, Suzhou 215028, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2010年 / 26卷 / 02期

关键词：

blood-brain barrier; Kringle; middle cerebral artery occlusion; ischemia; stroke; tissue plasminogen activator; DELETION MUTANT; ISCHEMIC-STROKE; PDGF-CC; BARRIER; EXPRESSION; INJURY; MICE; TPA; SEIZURE; NEURONS;

D O I：

10.3892/ijmm_00000456

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Tissue plasminogen activator (TPA) showed brain-protective activity within the first 15 min after cerebral ischemia in rats. To understand its molecular mechanism, TPA derivates were intracerebroventricularly administered at 15 min before, and 15, 90, 120 min after middle cerebral artery occlusion (MCAO) in rats. The reduction in mortality and cerebral infarction at 24 h was seen only with TPA administered at 15 min after MCAO. The down-regulation of endogenous TPA by the intracerebroventricular injection of TPA was found to be responsible for the protective effect on the integrity of blood-brain barrier after MCAO, as well as for the reduction in mortality and cerebral infarction. Moreover, for the first time we have found that the Kringle-2 domain is essential for the brain-protective activity of TPA.

引用

页码：225 / 230

页数：6

共 30 条

[1] Endogenous plasminogen activator expression after embolic focal cerebral ischemia in mice
Ahn, MY
Zhang, ZG
Tsang, W
Chopp, M
[J]. BRAIN RESEARCH, 1999, 837 (1-2) : 169 - 176
[2] Blood-brain barrier disruption and matrix metalloproteinase-9 expression during, reperfusion injury - Mechanical versus embolic focal ischemia in spontaneously hypertensive rats
Aoki, T
Sumii, T
Mori, T
Wang, XY
Lo, EH
[J]. STROKE, 2002, 33 (11) : 2711 - 2717
[3] Plasminogen activators contribute to impairment of hypercapnic and hypotensive cerebrovasodilation after cerebral hypoxia/ischemia in the newborn pig
Armstead, WM
Cines, DB
Higazi, AAR
[J]. STROKE, 2005, 36 (10) : 2265 - 2269
[4] EVALUATION OF 2, 3, 5-TRIPHENYLTETRAZOLIUM CHLORIDE AS A STAIN FOR DETECTION AND QUANTIFICATION OF EXPERIMENTAL CEREBRAL INFARCTION IN RATS
BEDERSON, JB
PITTS, LH
GERMANO, SM
NISHIMURA, MC
DAVIS, RL
BARTKOWSKI, HM
[J]. STROKE, 1986, 17 (06) : 1304 - 1308
[5] Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats
Belayev, L
Busto, R
Zhao, WZ
Ginsberg, MD
[J]. BRAIN RESEARCH, 1996, 739 (1-2) : 88 - 96
[6] Equivocal roles of tissue-type plasminogen activator in stroke-induced injury
Benchenane, K
López-Atalaya, JP
Fernández-Monreal, M
Touzani, O
Vivien, D
[J]. TRENDS IN NEUROSCIENCES, 2004, 27 (03) : 155 - 160
[7] Antiangiogenic activity of a domain deletion mutant of tissue plasminogen activator containing kringle 2
Carroll, VA
Nikitenko, LL
Bicknell, R
Harris, AL
[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (04) : 736 - 741
[8] THROMBOLYTIC THERAPY IN STROKE - POSSIBILITIES AND HAZARDS
DELZOPPO, GJ
ZEUMER, H
HARKER, LA
[J]. STROKE, 1986, 17 (04) : 595 - 607
[9] Tissue plasminogen activator is a potent activator of PDGF-CC
Fredriksson, L
Li, H
Fieber, C
Li, X
Eriksson, U
[J]. EMBO JOURNAL, 2004, 23 (19) : 3793 - 3802
[10] TISSUE-TYPE PLASMINOGEN-ACTIVATOR DOMAIN-DELETION MUTANT BM-06.022 - MODULAR STABILITY, INHIBITOR BINDING, AND ACTIVATION CLEAVAGE
HU, CK
KOHNERT, U
WILHELM, O
FISCHER, S
LLINAS, M
[J]. BIOCHEMISTRY, 1994, 33 (39) : 11760 - 11766

← 1 2 3 →