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

J Neurol Sci. 2010 Mar 15;290(1-2):90-5. doi: 10.1016/j.jns.2009.10.023. Epub 2009 Nov 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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