所属 埼玉医科大学 医学部 国際医療センター 神経内科・脳卒中内科 職種 教授
|Neuroprotective effects of clarithromycin against neuronal damage in cerebral ischemia and in cultured neuronal cells after oxygen-glucose deprivation
|PERGAMON-ELSEVIER SCIENCE LTD
|Yasuo Katayama,Toshiki Inaba,Chikako Nito,Satoshi Suda,Masayuki Ueda
|Aims: Rats subjected to transient focal ischemia and cultured neuronal cells subjected to oxygen-glucose deprivation (OGD) were treated with clarithromycin (CAM) to evaluate the effects of CAM in protecting against neuronal damage.
Main methods: Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 90 min and then reperfused. Each animal was given an oral dose clarithromycin (CAM, 100 mg/kg) or vehicle alone just after the ischemia was commenced. The infarct volume, edema index and neurological performance were assessed after 24 and 72 h of reperfusion. The cerebral blood flow (CBF) was measured with an MRI system at 90 min after MCAO. After 24 and 72 h, oxidative stress (4-HNE, 8-OHdG) and inflammation (lba-1,TNF-alpha) were assessed by immunohistochemical analyses and degenerative cells were assessed in the cortex by Fluoro-Jade C (FJC) labeling. The cultured neuronal cells were also used to examine the effects of CAM exposure on the viability of the cells after OGD.
Key findings: CBF was unchanged between the two groups. Significant reductions of the infarct volume and edema index, an improved neurological deficit score, a significant suppression of 4-HNE and 8-OHdG expression, marked reductions of lba-1 and TNF-alpha expression, and a significant reduction of FJC-positive cells were also observed in the CAM-treated animals at both time points. Treatment with 10 mu M and 100 mu M CAM in vitro significantly reduced cell death after OGD.
Significance: CAM appears to provide antioxidant and anti-inflammatory effects and protect against neuronal damage after cerebral ischemia and OGD. (C) 2016 Elsevier Inc. All rights reserved.