title: 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: Department of Pharmacology, Alma Mater Studiorum, University of Bologna, Via Irnerio 48-40126 Bologna, Italy.
authors: Donatella
authors: D
authors: Canistro
authors: Alessandra A
authors: AA
authors: Affatato
authors: Antonio
authors: A
authors: Soleti
authors: Vincenzo
authors: V
authors: Mollace
authors: Carolina
authors: C
authors: Muscoli
authors: Francesca
authors: F
authors: Sculco
authors: Iolanda
authors: I
authors: Sacco
authors: Valeria
authors: V
authors: Visalli
authors: Barbara
authors: B
authors: Bonamassa
authors: Manuela
authors: M
authors: Martano
authors: Michelangelo
authors: M
authors: Iannone
authors: Andrea
authors: A
authors: Sapone
authors: Moreno
authors: M
authors: Paolini
mesh_terms: D000818:Animals; D001925:Brain Damage, Chronic / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D020520:Brain Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D016893:Carotid Stenosis / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D007263:Infusions, Parenteral; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D010880:Piperidines; C526136:bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate