A Retinoic Acid Receptor Agonist Am80 Rescues Neurons, Attenuates Inflammatory Reactions, and Improves Behavioral Recovery after Intracerebral Hemorrhage in Mice
Open Access
- 16 June 2010
- journal article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 31 (1), 222-234
- https://doi.org/10.1038/jcbfm.2010.80
Abstract
Am80 (tamibarotene) is a retinoic acid receptor (RAR) agonist clinically available for treatment of acute promyelocytic leukemia. As intracerebral hemorrhage (ICH) accompanies inflammatory reactions in the brain and also because retinoids may suppress activation of microglia, we investigated the effect of Am80 on collagenase-induced experimental model of ICH in adult mice. Daily oral administration of Am80 (5 mg/kg) starting from 1 day before or from up to 6 hours after intrastriatal injection of collagenase significantly inhibited the decrease in the number of striatal neurons at 3 days after the insult. Am80 showed no significant effect on the hematoma size and the extent of edema associated with hemorrhage. Prominent expression of RARα was observed in activated microglia/macrophages, and the number of activated microglia/macrophages in the perihematoma region was lower in Am80-treated mice than in vehicle-treated mice. Am80 treatment also reduced areas affected by hemorrhage-associated oxidative stress as indicated by nitrotyrosine immunoreactivity, and attenuated heme oxygenase-1 expression in activated microglia/macrophages. Moreover, Am80-treated mice exhibited better recovery from hemorrhage-induced neurologic deficits than vehicle-treated mice. These results suggest that RAR is a promising target of neuroprotective therapy for ICH.Keywords
This publication has 37 references indexed in Scilit:
- Regulation of haeme oxygenase‐1 for treatment of neuroinflammation and brain disordersBritish Journal of Pharmacology, 2008
- Edaravone Attenuates Brain Edema and Neurologic Deficits in a Rat Model of Acute Intracerebral HemorrhageStroke, 2008
- Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alphaProceedings of the National Academy of Sciences, 2007
- Retinoic acid in the development, regeneration and maintenance of the nervous systemNature Reviews Neuroscience, 2007
- Minocycline protects the blood–brain barrier and reduces edema following intracerebral hemorrhage in the ratExperimental Neurology, 2007
- Inflammation after Intracerebral HemorrhageJournal of Cerebral Blood Flow & Metabolism, 2006
- 9-Cis-retinoic acid suppresses inflammatory responses of microglia and astrocytesJournal of Neuroimmunology, 2006
- Mechanisms of brain injury after intracerebral haemorrhageThe Lancet Neurology, 2006
- Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult ratsBrain Research, 2004
- Comparison of brain cell death and inflammatory reaction in three models of intracerebral hemorrhage in adult ratsJournal Of Stroke & Cerebrovascular Diseases, 2003