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

Abstract	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.
Authors	Haitao Zhang, Feng Bi, Chunlan Xiao, Jianxia Liu, Zhixia Wang, Jian-Ning Liu, Jing Zhang
Journal	International journal of molecular medicine (Int J Mol Med) Vol. 26 Issue 2 Pg. 225-30 (Aug 2010) ISSN: 1791-244X [Electronic] Greece
PMID	20596602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	NF-kappa B Protective Agents Recombinant Proteins reteplase Tissue Plasminogen Activator Matrix Metalloproteinase 9
Topics	Analysis of Variance Animals Blood-Brain Barrier (drug effects) Brain Infarction (prevention & control) Cerebrum (drug effects, metabolism) Chi-Square Distribution Disease Models, Animal Gene Expression (drug effects) Infarction, Middle Cerebral Artery (drug therapy, metabolism) Kringles Male Matrix Metalloproteinase 9 (genetics, metabolism) NF-kappa B (genetics, metabolism) Protective Agents (administration & dosage, pharmacology, therapeutic use) Protein Structure, Tertiary Rats Rats, Sprague-Dawley Recombinant Proteins (administration & dosage, pharmacology, therapeutic use) Tissue Plasminogen Activator (administration & dosage, drug effects, metabolism, pharmacology, therapeutic use)

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