Neuroprotective effects of clarithromycin against neuronal damage in cerebral ischemia and in cultured neuronal cells after oxygen-glucose deprivation

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• 作者：Yasuo Katayama ; MD ; PhD^a ; ^b ; ^{yasuo.katayama@mt.strins.or.jp} ; Toshiki Inaba^c ; ¹ ; Chikako Nito ; MD ; PhD^c ; ¹ ; Satoshi Suda ; MD ; PhD^c ; Masayuki Ueda ; MD ; PhD^c
• 关键词：Clarithromycin ; Neuroprotection ; Antioxidant action ; Anti-inflammatory action ; Focal cerebral ischemia ; Oxygen-glucose deprivation (OGD)
• 刊名：Life Sciences
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：168
• 期：Complete
• 页码：7-15
• 全文大小：1469 K
• 卷排序：168

文摘

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 methodsSprague-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 (Iba-1, TNF-α) 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 findingsCBF 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 Iba-1 and TNF-α expression, and a significant reduction of FJC-positive cells were also observed in the CAM-treated animals at both time points. Treatment with 10 μM and 100 μM CAM in vitro significantly reduced cell death after OGD.SignificanceCAM appears to provide antioxidant and anti-inflammatory effects and protect against neuronal damage after cerebral ischemia and OGD.