title: Protective effects of catalpol on oligodendrocyte death and myelin breakdown in a rat model of chronic cerebral hypoperfusion.
abstract: Chronic cerebral hypoperfusion is thought to induce white matter lesions (WMLs) with oligodendrocyte (OLG) death and myelin breakdown. Although apoptosis is believed to be involved in the pathologic process of WMLs, effective therapies for such remain lacking. In the present study, we investigated whether catalpol, an iridoid glycoside, could act on oligodendrocytes (OLGs) and myelin sheaths in a rat chronic hypoperfusion model, and whether transcription factor cAMP-responsive element binding protein (CREB) phosphorylation is involved in the resulting neuroprotection. A rat model of chronic cerebral hypoperfusion was prepared by bilateral common carotid artery ligation. On the 30th day after hypoperfusion, OLG loss and myelin disruption in the ischemic white matter were more severe and evident than in the sham control. Spatial memory was also more seriously impaired in rats after hypoperfusion. Treatment with catalpol significantly suppressed diminished OLGs and myelin breakdown, and promoted the recovery of cognitive decline. The expression of Bcl-2 and phosphorylated CREB (p-CREB) was also significantly increased by catalpol treatment. In conclusion, catalpol could protect against hypoperfusion-induced WMLs and cognitive impairment through the p-CREB signaling pathway leading to downstream upregulation of Bcl-2. Our results suggest that catalpol may be a useful approach for treating cerebrovascular WMLs.
authors.affiliation: Department of Histology and Embryology, College of Basic Medicine, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Qi-Yan
authors.initials: QY
authors.lastname: Cai
authors.forename: Xing-Shu
authors.initials: XS
authors.lastname: Chen
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Zhan
authors.forename: Zhong-Xiang
authors.initials: ZX
authors.lastname: Yao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology*; D050882:CREB-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects* / Q000473:pathology; D010766:Phosphorylation; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D000644:Quaternary Ammonium Compounds; C031490:catamine AB; D050882:CREB-Binding Protein