Pharmacological preconditioning by milrinone: memory preserving and neuroprotective effect in ischemia-reperfusion injury in mice.

Abstract

We tested the neuroprotective effect of milrinone, a phosphodiesterase III inhibitor, in pharmacological preconditioning. Bilateral carotid artery occlusion for 12 min followed by reperfusion for 24 h produced ischemia-reperfusion (I/R) cerebral injury in male Swiss albino mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using the Morris water maze test, and motor coordination was evaluated using the inclined beam walking test, rota-rod test, and lateral push test. Milrinone (50 microg/kg & 100 microg/kg i.v.) was administered 24 h before surgery in a separate group of animals to induce pharmacological preconditioning. I/R increased cerebral infarct size and impaired memory and motor coordination. Milrinone treatment significantly decreased cerebral infarct size and reversed I/R-induced impairments in memory and motor coordination. This neuroprotective effect was blocked by ruthenium red (3 mg/kg, s.c.), an intracellular ryanodine receptor blocker. These findings indicate that milrinone preconditioning exerts a marked neuroprotective effect on the ischemic brain, putatively due to increased intracellular calcium levels activating calcium-sensitive signal transduction cascades.

• Authors: Reetu Saklani, Amteshwar Jaggi, Nirmal Singh
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 33 Issue 7 Pg. 1049-57 (Jul 2010) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 20661715 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Neuroprotective Agents
• Milrinone

Topics

• Animals
• Brain Ischemia (drug therapy, physiopathology, prevention & control)
• Ischemic Preconditioning (methods)
• Male
• Maze Learning (drug effects, physiology)
• Memory Disorders (drug therapy, physiopathology, prevention & control)
• Mice
• Milrinone (therapeutic use)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Reperfusion Injury (drug therapy, physiopathology, prevention & control)