Blood micromolar concentrations of kaempferol afford protection against ischemia/reperfusion-induced damage in rat brain

Abstract The slow time course of neurodegeneration after brain ischemia/reperfusion opened a realistic time window for the application of protective therapies to prevent spreading of brain damage. In this work, we studied the ability of micromolar concentrations of this flavonoid in the blood to pro...

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Bibliographic Details
Published in:Brain research 2007-11, Vol.1182, p.123-137
Main Authors: López-Sánchez, Carmen, Martín-Romero, Francisco Javier, Sun, Fei, Luis, Laura, Samhan-Arias, Alejandro K, García-Martínez, Virginio, Gutiérrez-Merino, Carlos
Format: Article
Language:English
Subjects:
Animal models of human disease
Animals
Biological and medical sciences
Brain - drug effects
Brain - pathology
Brain ischemia/reperfusion
Brain protection against apoptosis
Caspase 9 - metabolism
Cell Death - drug effects
Collagen Type XI - metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
In Situ Nick-End Labeling - methods
Infarction, Middle Cerebral Artery - physiopathology
Kaempferol
Kaempferols - blood
Kaempferols - therapeutic use
Laminin - metabolism
Male
Matrix Metalloproteinase 9 - metabolism
Medical sciences
Neurology
Neuroprotective Agents - blood
Neuroprotective Agents - therapeutic use
Protection against brain oxidative stress
Rats
Rats, Wistar
Reperfusion Injury - pathology
Reperfusion Injury - prevention & control
Statistics, Nonparametric
Tetrazolium Salts
Thiazoles
Thiobarbituric Acid Reactive Substances - metabolism
Time Factors
Transient ischemic attack
Vascular diseases and vascular malformations of the nervous system
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Summary:Abstract The slow time course of neurodegeneration after brain ischemia/reperfusion opened a realistic time window for the application of protective therapies to prevent spreading of brain damage. In this work, we studied the ability of micromolar concentrations of this flavonoid in the blood to protect against brain damage induced by transient focal cerebral ischemia in rats. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion in adult rats and brain damage has been monitored by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin–eosin (H–E) staining, ‘in situ’ terminal deoxyribonucleotidyl transferase-mediated dUTP-fluorescein nick end labeling (TUNEL), ‘in situ’ metalloproteinase activity using DQ-gelatin and loss of anti-laminin staining. Intravenous injections of kaempferol, at a dose of 10–15 μmol/L of blood 30 min before the induction of a 60 min ischemia-episode and just after reperfusion, led to > 90% and 70–80% (TTC, H–E, TUNEL) decrease of brain damage in the temporal–frontal areas of neocortex and striatum, respectively, but only 40–50% decrease of brain damage was observed in the hippocampus and vicinal caudal areas of the striatum. This treatment with kaempferol also produced a similar reduction of metalloproteinase activation and loss of anti-laminin staining in cortical and striatum infarct areas. Kaempferol treatment efficiently protected against nitrosative-oxidative stress after ischemia/reperfusion, as shown by nearly complete protection against the increase of protein nitrotyrosines, and also afforded strong protection against the increase of apoptotic cell death (TUNEL) and biochemical markers of apoptosis, such as caspase-9 activity and poly-(ADP-ribose) polymerase degradation. On these grounds, a potential new therapeutic role of kaempferol to acute treatment of ischemic stroke is suggested.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2007.08.087