title: Neuroprotective effects of erythromycin on ischemic injury following permanent focal cerebral ischemia in rats.
abstract: OBJECTIVE
  This study aims to determine if erythromycin provides neuroprotective effects against ischemic injury following permanent focal cerebral ischemia.
  
  
  METHODS
  Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). Each animal received a single subcutaneous injection of erythromycin lactobionate (EM, 50 mg/kg) or vehicle immediately after ischemia. The infarct volume, edema index and neurological performance were evaluated at 24 and 72 h after MCAO. The cerebral blood flow (CBF) was measured with an MRI system at 30 min after MCAO. TUNEL staining and immunohistochemical analyses for oxidative stress (4-HNE, 8-OHdG) and inflammation (Iba-1, TNF-α) in the cortex were conducted at 24 and 72 h after MCAO.
  
  
  RESULTS
  The CBF did not differ between the EM-treated and vehicle-treated groups. The EM treatment significantly reduced the infarct volume (p < 0.01) at 24 and 72 h after MCAO and significantly reduced the edema index (p < 0.01) at 24 h. The EM treatment significantly improved the neurological deficit scores (p < 0.05) at 24 and 72 h. EM also 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 < 0.05) at both time points. The EM treatment significantly reduced TUNEL-positive cells (p < 0.01) at both time points.
  
  
  CONCLUSIONS
  These findings suggest that EM can protect against the neuronal damage caused by cerebral ischemia by alleviating inflammation and reducing oxidant stress.
authors.affiliation: a Department of Neurology and Stroke Center , Tokyo General Hospital , Tokyo , Japan.|b Graduate School of Medicine , Nippon Medical School , Tokyo , Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Katayama
authors.affiliation: c Department of Neurological Science, Graduate School of Medicine , Nippon Medical School , Tokyo , Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Inaba
authors.affiliation: c Department of Neurological Science, Graduate School of Medicine , Nippon Medical School , Tokyo , Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nito
authors.affiliation: c Department of Neurological Science, Graduate School of Medicine , Nippon Medical School , Tokyo , Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ueda
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004917:Erythromycin / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008840:Microfilament Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D018709:Statistics, Nonparametric; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D000447:Aldehydes; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D004917:Erythromycin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal
keywords: Anti-inflammatory action; Antioxidant action; Erythromycin; Permanent ischemia