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.
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.
Asanuma
Taketoshi
T
Laboratory of Radiation Biology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Inanami
Osamu
O
Tabu
Kouichi
K
Waki
Kenji
K
Kon
Yasuhiro
Y
Kuwabara
Mikinori
M
D000818:Animals; D002545:Brain Ischemia / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D002463:Cell Membrane Permeability / Q000187:drug effects; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015696:Gene Products, tat / Q000494:pharmacology / Q000627:therapeutic use*; D048031:JNK Mitogen-Activated Protein Kinases; D008279:Magnetic Resonance Imaging; D008297:Male; D008314:Malonates / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D015696:Gene Products, tat; D008314:Malonates; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C030290:malonic acid; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases