title: Neuroprotective effects of erythromycin on cerebral ischemia reperfusion-injury and cell viability after oxygen-glucose deprivation in cultured neuronal cells.
abstract: This study aims to determine if erythromycin has neuroprotective effects against transient ischemia and oxygen-glucose deprivation (OGD) in cultured neuronal cells. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 90 min, followed by reperfusion. The animals received a subcutaneous single injection of erythromycin lactobionate (EM, 50mg/kg) or vehicle immediately after ischemia. Infarct volume, edema index, and neurological performance were evaluated at 24 and 72 h after reperfusion. Immunohistochemical analyses for oxidative stress (4-HNE, 8-OHdG) and inflammation (Iba-1, TNF-α) were conducted in the cortex at 24h. Primary cortical neuronal cell cultures were prepared from the cerebral cortices of the animals and then subjected to OGD for 3h. Ten or 100 μM EM was added before OGD to determine the effect of EM on cell viability after OGD. EM significantly reduced infarct volume (p<0.01) and edema volume (p<0.05) and improved neurological deficit scores (p<0.05) at 24 and 72 h. EM significantly suppressed the accumulation of 4-HNE (p<0.01) and 8-OHdG (p<0.01) and markedly reduced Iba-1 (p<0.01) and TNF-α expression (p<0.01). Treatment with 100 μM EM in vitro significantly reduced cell death after OGD. EM reduces neuronal damage following cerebral ischemia and OGD and may have antioxidant and anti-inflammatory effects.
authors.affiliation: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan; Department of Neurology and Stroke Center, Tokyo General Hospital, 3-15-2 Ekoda, Nakano-ku, Tokyo 165-8906, Japan. Electronic address: yasuo.katayama@mt.strins.or.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Katayama
authors.affiliation: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Inaba
authors.affiliation: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nito
authors.affiliation: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Katsura
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004917:Erythromycin / Q000008:administration & dosage*; D005947:Glucose / Q000172:deficiency; D006429:Hemiplegia / Q000209:etiology / Q000517:prevention & control; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018696:Neuroprotective Agents; D004917:Erythromycin; D005947:Glucose
keywords: Erythromycin; Focal ischemia; Inflammation; Neuroprotection; OGD