HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Calpain inhibitor entrapped in liposome rescues ischemic neuronal damage.

Abstract
Transient forebrain ischemia induces activation of calpain and proteolysis of a neuronal cytoskeleton, fodrin, in gerbil hippocampus. This phenomenon precedes delayed neuronal death in hippocampal CA1 neurons. We examined effects of a calpain inhibitor on delayed neuronal death after transient forebrain ischemia. In gerbils, a selective calpain inhibitor entrapped in liposome was given transvenously and 30 min later, 5-min forebrain ischemia was produced by occlusion of both common carotid arteries. On day 7, CA1 neuronal damage was examined in the hippocampal slices stained with cresyl violet. Calpain-induced proteolysis of fodrin was also examined by immunohistochemistry and immunoblot. Additionally, to assure entrapment of the inhibitor by CA1 neurons, the inhibitor-liposome complex was labeled with FITC and given to gerbils. Fluorescence in the hippocampal slices was examined by confocal laser scanning microscope. Selective CA1 neuronal damage induced by forebrain ischemia was prevented by administration of the inhibitor in a dose-dependent manner. Calpain-induced proteolysis of fodrin was also extinguished by the calpain inhibitor in a dose-dependent manner. Bright fluorescence of the FITC-labeled inhibitor was observed in the CA1 neurons. The data show an important role of calpain in the development of the ischemic delayed neuronal death. Calpain seems to produce neuronal damage by degrading neuronal cytoskeleton. Our data also show a palliative effect of the calpain inhibitor on the neurotoxic damage, which offers a new and potent treatment of transient forebrain cerebral ischemia.
AuthorsM Yokota, E Tani, S Tsubuki, I Yamaura, I Nakagaki, S Hori, T C Saido
JournalBrain research (Brain Res) Vol. 819 Issue 1-2 Pg. 8-14 (Feb 20 1999) ISSN: 0006-8993 [Print] Netherlands
PMID10082855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 1999 Elsevier Science B.V.
Chemical References
  • Carrier Proteins
  • Cysteine Proteinase Inhibitors
  • Drug Carriers
  • Fluorescent Dyes
  • Leupeptins
  • Liposomes
  • Microfilament Proteins
  • fodrin
  • acetylleucyl-leucyl-norleucinal
  • Calpain
  • Fluorescein-5-isothiocyanate
Topics
  • Animals
  • Blood-Brain Barrier
  • Blotting, Western
  • Calpain (antagonists & inhibitors)
  • Carrier Proteins (metabolism)
  • Cell Death (drug effects)
  • Cysteine Proteinase Inhibitors (administration & dosage, pharmacology)
  • Dose-Response Relationship, Drug
  • Drug Carriers
  • Fluorescein-5-isothiocyanate
  • Fluorescent Dyes
  • Gerbillinae
  • Hippocampus (drug effects, metabolism, pathology)
  • Immunohistochemistry
  • Injections, Intravenous
  • Ischemic Attack, Transient (drug therapy, pathology)
  • Leupeptins (administration & dosage, pharmacology)
  • Liposomes
  • Microfilament Proteins (metabolism)
  • Microscopy, Confocal
  • Neurons (drug effects, pathology)
  • Prosencephalon (blood supply, drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: