Caffeinol is currently being tested in
acute ischemic stroke patients. However, little is known about the pharmacology or safety of
caffeinol in preclinical
embolic stroke models. We determined the pharmacological effects of
caffeinol administration on clinical rating scores in rabbits following small clot
embolic strokes (RSCEM). Male New Zealand white rabbits were embolized by injecting
blood clots into the cerebral circulation via a carotid
catheter. Behavioral analysis was conducted 24 h following embolization, allowing for the determination of the effective
stroke dose (P50) or clot amount (mg) that produces neurological deficits in 50% of the rabbits. In the current study, the P50 values for the control groups were 1.32 +/- 0.23 and 1.66 +/- 0.29 mg for the bolus-injected and infused groups, respectively. Rabbits treated with
caffeinol (bolus) starting 15 min following embolization had a P50 value of 1.70 +/- 1.18 mg.
Caffeinol-infused rabbits had a P50 value of 2.05 +/- 0.47 and 1.67 +/- 0.48 mg for low- and high-dose
ethanol, respectively. In tPA-treated rabbits (0.9 mg/kg), the group P50 was 1.58 +/- 0.43 mg. In
caffeinol (bolus) and tPA-treated rabbits, we measured a decrease in the P50 value to 0.70 +/- 0.30 mg and an increase in the rate of
intracerebral hemorrhage compared to control. This primary finding of this study indicates that neither bolus-injected nor infused
caffeinol affects behavioral deficits following
embolic strokes in rabbits. Moreover, the combination of
caffeinol plus low-dose tPA does not improve behavioral deficits. However, our study suggests that there is the potential for exacerbation of
stroke-induced behavioral deficits following
caffeinol administration in combination with a thrombolytic that may be related to increased
intracerebral hemorrhage.