A combined treatment with tacrolimus (FK506) and recombinant tissue plasminogen activator for thrombotic focal cerebral ischemia in rats: increased neuroprotective efficacy and extended therapeutic time window.

Abstract

The authors evaluated the therapeutic efficacy of tacrolimus (FK506), administered alone or in combination with recombinant tissue plasminogen activator (t-PA), on brain infarction following thrombotic middle cerebral artery (MCA) occlusion. Thrombotic occlusion of the MCA was induced by a photochemical reaction between rose bengal and green light in Sprague-Dawley rats, and the volume of ischemic brain damage was determined 24 hours later. Intravenous administration of tacrolimus or t-PA dose-dependently reduced the volume of ischemic brain infarction, whether administered immediately or 1 hour after MCA occlusion. When tacrolimus or t-PA was administered 2 hours after MCA occlusion, each drug showed a tendency to reduce ischemic brain damage. However, combined treatment with both drugs resulted in a significant reduction in ischemic brain damage. On administration 3 hours after MCA occlusion, tacrolimus alone showed no effect, and t-PA tended to worsen ischemic brain damage. However, the combined treatment with both drugs not only ameliorated the worsening trend seen with t-PA alone, but also tended to reduce ischemic brain damage. In conclusion, tacrolimus, used in combination with t-PA, augmented therapeutic efficacy on brain damage associated with focal ischemia and extended the therapeutic time window compared to single-drug treatments.

• Authors: Masashi Maeda, Yasuhisa Furuichi, Noriko Ueyama, Akira Moriguchi, Natsuki Satoh, Nobuya Matsuoka, Toshio Goto, Takehiko Yanagihara
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 22 Issue 10 Pg. 1205-11 (Oct 2002) ISSN: 0271-678X [Print] United States
• PMID: 12368659 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Neuroprotective Agents
• Tissue Plasminogen Activator
• Tacrolimus

Topics

• Animals
• Blood Flow Velocity (drug effects)
• Cerebrovascular Circulation (drug effects, physiology)
• Disease Models, Animal
• Drug Therapy, Combination
• Intracranial Thrombosis (drug therapy, pathology)
• Ischemic Attack, Transient (drug therapy, pathology)
• Male
• Middle Cerebral Artery (drug effects, pathology)
• Neuroprotective Agents (administration & dosage, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Tacrolimus (administration & dosage, therapeutic use)
• Time Factors
• Tissue Plasminogen Activator (administration & dosage, therapeutic use)