BACKGROUND AND PURPOSE: Although caffeinol (a combination of a low dose of caffeine and ethanol) was shown to robustly reduce stroke damage in experimental models and is now in clinical evaluation for treatment of ischemic stroke, little is known about the potential mechanism of its action. METHODS: We used an in vivo excitotoxicity model based on intracortical infusion of N-methyl-D-aspartate (NMDA) and a model of reversible focal ischemia to demonstrate NMDA receptor inhibition as a potential mechanism of caffeinol anti-ischemic activity. RESULTS: Caffeinol reduced the size of excitotoxic lesion, and substitution of ethanol in caffeinol with the NMDA antagonists CNS-1102 and MK-801 but not with MgSO(4) produced treatment with strong synergistic effect that was at least as robust in reducing ischemic damage as caffeinol. This NMDA receptor antagonist and caffeine combination demonstrated a long window of opportunity, activity in spontaneously hypertensive rats, and, unlike caffeinol, was fully effective in animals chronically pretreated with ethanol. CONCLUSIONS: Our study suggests that antiexcitotoxic properties may underlie some of the anti-ischemic effect of caffeinol. This study provides strong evidence that the anti-ischemic effect of NMDA receptor blockers in general can be dramatically augmented by caffeine, thus opening a possibility for new use of NMDA-based pharmacology in the treatment of stroke.
BACKGROUND AND PURPOSE: Although caffeinol (a combination of a low dose of caffeine and ethanol) was shown to robustly reduce stroke damage in experimental models and is now in clinical evaluation for treatment of ischemic stroke, little is known about the potential mechanism of its action. METHODS: We used an in vivo excitotoxicity model based on intracortical infusion of N-methyl-D-aspartate (NMDA) and a model of reversible focal ischemia to demonstrate NMDA receptor inhibition as a potential mechanism of caffeinol anti-ischemic activity. RESULTS:Caffeinol reduced the size of excitotoxic lesion, and substitution of ethanol in caffeinol with the NMDA antagonists CNS-1102 and MK-801 but not with MgSO(4) produced treatment with strong synergistic effect that was at least as robust in reducing ischemic damage as caffeinol. This NMDA receptor antagonist and caffeine combination demonstrated a long window of opportunity, activity in spontaneously hypertensiverats, and, unlike caffeinol, was fully effective in animals chronically pretreated with ethanol. CONCLUSIONS: Our study suggests that antiexcitotoxic properties may underlie some of the anti-ischemic effect of caffeinol. This study provides strong evidence that the anti-ischemic effect of NMDA receptor blockers in general can be dramatically augmented by caffeine, thus opening a possibility for new use of NMDA-based pharmacology in the treatment of stroke.
Authors: Sheryl Martin-Schild; Hen Hallevi; Hashem Shaltoni; Andrew D Barreto; Nicole R Gonzales; Jarek Aronowski; Sean I Savitz; James C Grotta Journal: J Stroke Cerebrovasc Dis Date: 2009 Mar-Apr Impact factor: 2.136
Authors: Anthony Zulli; Renee M Smith; Peter Kubatka; Jan Novak; Yoshio Uehara; Hayley Loftus; Tawar Qaradakhi; Miroslav Pohanka; Nazarii Kobyliak; Angela Zagatina; Jan Klimas; Alan Hayes; Giampiero La Rocca; Miroslav Soucek; Peter Kruzliak Journal: Eur J Nutr Date: 2016-03-01 Impact factor: 5.614
Authors: Cesar Reis; Onat Akyol; Wing Mann Ho; Camila Araujo; Lei Huang; Richard Applegate; John H Zhang Journal: Biomed Res Int Date: 2017-02-14 Impact factor: 3.411