The novel radical scavenger IAC is effective in preventing and protecting against post-ischemic brain damage in Mongolian gerbils.

Abstract

The removal of pathologically generated free radicals produced during ischemia, reperfusion and intracranical hemorrhage seems to be a viable approach to neuroprotection. However, at present, no neuroprotective agent has proven effective in focal ischemic stroke phase III trials, despite the encouraging data in animal models. This study aimed to explore the effect of the brain penetrant low molecular weight radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) in neurological damage subsequent to ischemia-reperfusion injury in Mongolian gerbils. We examined the intraperitoneal effects of IAC on temporary bilateral common carotid artery occlusion (BCCO) by means of morphological and histological analysis of the hippocampus. Significant dose-dependent protective effects of IAC (1 to 10mg/kg b.w.) against neuropathological and morphological brain changes were seen when administered i.p. 1h before temporary BCCO in Mongolian gerbils. When administered up to 6h after BCCO, IAC actually reverses the neurodegenerative processes (e.g. hippocampal cell viability) induced by ischemia in a dose-dependent fashion. Data show that IAC is highly effective in protecting and preventing oxidative brain damage associated with cerebral flow disturbances. It is also effective even in late treatment of the insult, emphasizing its potential role for the management of ischemic stroke patients.

• Authors: Donatella Canistro, Alessandra A Affatato, Antonio Soleti, Vincenzo Mollace, Carolina Muscoli, Francesca Sculco, Iolanda Sacco, Valeria Visalli, Barbara Bonamassa, Manuela Martano, Michelangelo Iannone, Andrea Sapone, Moreno Paolini
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 290 Issue 1-2 Pg. 90-5 (Mar 15 2010) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 19945716 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Free Radical Scavengers
• Neuroprotective Agents
• Piperidines
• bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate

Topics

• Animals
• Brain Damage, Chronic (drug therapy, physiopathology, prevention & control)
• Brain Infarction (drug therapy, physiopathology, prevention & control)
• Brain Ischemia (complications, drug therapy, physiopathology)
• Carotid Stenosis (complications, drug therapy, physiopathology)
• Cell Survival (drug effects, physiology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Free Radical Scavengers (pharmacology, therapeutic use)
• Gerbillinae
• Hippocampus (blood supply, drug effects, pathology)
• Infusions, Parenteral
• Male
• Nerve Degeneration (drug therapy, physiopathology, prevention & control)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxidative Stress (drug effects, physiology)
• Piperidines (pharmacology, therapeutic use)
• Treatment Outcome