Natural and synthetic retinoids afford therapeutic effects on intracerebral hemorrhage in mice
| Autor: | Yoichiro Isohama, Hideaki Matsushita, Koichi Shudo, Hiroshi Katsuki, Akinori Hisatsune, Masanori Hijioka |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Agonist Time Factors Tetrahydronaphthalenes Receptors Retinoic Acid medicine.drug_class Cell Count Tretinoin Pharmacology Benzoates Mice Retinoids chemistry.chemical_compound Hematoma Bacterial Proteins Animals Medicine Collagenases Cerebral Hemorrhage Neurons Intracerebral hemorrhage Dose-Response Relationship Drug Microglia business.industry Macrophages Brain Macrophage Activation medicine.disease Mice Inbred C57BL Disease Models Animal Retinoic acid receptor Microbial Collagenase Neuroprotective Agents medicine.anatomical_structure chemistry Anesthesia Tamibarotene Psychomotor Disorders business Psychomotor disorder medicine.drug |
| Zdroj: | European Journal of Pharmacology. 683:125-131 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2012.03.023 |
| Popis: | We have recently proposed that retinoic acid receptor (NR1B) is a promising target of neuroprotective therapy for intracerebral hemorrhage, since pretreatment of mice with an NR1B1/NR1B2 agonist Am80 attenuated various pathological and neurological abnormalities associated with the disease. In the present study we further addressed the effects of retinoids as potential therapeutic drugs, using a collagenase-induced model of intracerebral hemorrhage. Daily oral administration of all-trans retinoic acid (ATRA; 5 and 15 mg/kg), a naturally occurring NR1B agonist, from 1 day before collagenase injection significantly inhibited loss of neurons within the hematoma. ATRA in the same treatment regimen also decreased the number of activated microglia/macrophages around the hematoma but did not affect the hematoma volume. ATRA (15 mg/kg) as well as Am80 (5mg/kg) rescued neurons in the central region of hematoma, even when drug administration was started from 6h after induction of intracerebral hemorrhage. However, in this post-treatment regimen, only Am80 significantly decreased the number of activated microglia/macrophages. With regard to neurological deficits, both ATRA (15 mg/kg) and Am80 (5mg/kg) given in the post-treatment regimen improved performance of mice in the beam-walking test and the modified limb-placing test. ATRA and Am80 also significantly attenuated damage of axon tracts as revealed by amyloid precursor protein immunohistochemistry. These results underscore potential therapeutic values of NR1B agonists for intracerebral hemorrhage. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect