Protection against malonate-induced ischemic brain injury in rat by a cell-permeable peptidic c-Jun N-terminal kinase inhibitor, (L)-HIV-TAT48-57-PP-JBD20, observed by the apparent diffusion coefficient mapping magnetic resonance imaging method.

Abstract	The present experiments were carried out to provide direct in vivo evidence for the involvement of c-Jun N-terminal kinase (JNK) in the induction of ischemic brain injury. Malonate, which produces lesions similar to those of focal ischemia-reperfusion by a reversible inhibition of succinate dehydrogenase in mitochondria, was injected into the left striatum in the rat brain without or with the simultaneous injection of a cell permeable peptidic JNK inhibitor, (L)-HIV-TAT48-57-PP-JBD20. Two regions of malonate-induced brain injury were visualized as a hyperintense region with surrounding hypointense regions by apparent diffusion coefficient mapping magnetic resonance imaging. The JNK inhibitor significantly counteracted both hyper- and hypointense regions at the early stage of brain injury. Histological examination clarified that the inhibitor suppressed the induction of coagulation necrosis and spongy degeneration at early and late stages.
Authors	Taketoshi Asanuma, Osamu Inanami, Kouichi Tabu, Kenji Waki, Yasuhiro Kon, Mikinori Kuwabara
Journal	Neuroscience letters (Neurosci Lett) Vol. 359 Issue 1-2 Pg. 57-60 (Apr 08 2004) ISSN: 0304-3940 [Print] Ireland
PMID	15050711 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Enzyme Inhibitors Gene Products, tat Malonates Neuroprotective Agents Peptide Fragments malonic acid JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases
Topics	Animals Brain Ischemia (chemically induced, enzymology, prevention & control) Cell Membrane Permeability (drug effects) Diffusion Magnetic Resonance Imaging (methods) Enzyme Inhibitors (pharmacology, therapeutic use) Gene Products, tat (pharmacology, therapeutic use) JNK Mitogen-Activated Protein Kinases Magnetic Resonance Imaging Male Malonates (toxicity) Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism) Neuroprotective Agents (pharmacology, therapeutic use) Peptide Fragments (pharmacology, therapeutic use) Rats Rats, Sprague-Dawley

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