title: Monosialotetrahexosy-1 ganglioside attenuates diabetes-associated cerebral ischemia/reperfusion injury through suppression of the endoplasmic reticulum stress-induced apoptosis.
abstract: We aimed to assess the neuroprotective mechanism of monosialotetrahexosy-1 ganglioside (GM1) on focal cerebral ischemia/reperfusion (I/R) injury in rats with diabetes. A total of 54 male Wistar rats were induced with diabetes mellitus by administration of streptozotocin (STZ). The rats were then randomized into three groups, including sham group (n=18), I/R group (n=18), and GM1 group (n=18). Focal cerebral ischemia was modeled using the right middle cerebral artery occlusion method. In the GM1 group, diabetic rats were intraperitoneally administered with GM1 (15mg/kg) at 20min prior to reperfusion. GM1 was replaced by an equal volume of saline in the I/R group. Rats from the sham group accepted sham operation and normal saline. The neurological deficit and brain infarct volume and TUNEL-apoptosis were evaluated. The expression of endoplasmic reticulum (ER) stress-related proteins, including caspase-12, GRP78 and CHOP/GADD153, was examined by Western blot. GM1 notably reduced the cerebral infarct size and improved the neurological behavior. In addition, GM1 dramatically reduced TUNEL-positive cell numbers in the cerebral cortex. Furthermore, GM1 treatment modulated protein levels, increasing GRP78 and reducing CHOP/GADD153 expression along with activation of caspase-12 in the ischemic brain hemispheres. These results imply that GM1 attenuates diabetes-associated cerebral I/R injury by suppressing the ER stress-induced apoptosis.
authors.affiliation: Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: Sudanying2006@sina.com.
authors.forename: Danying
authors.initials: D
authors.lastname: Su
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin, China. Electronic address: Jingma2009@aliyun.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Harbin Medical University, Harbin, China. Electronic address: 1605711601@qq.com.
authors.forename: Jiachen
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: Zhangyansheng009@sina.com.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: chaocuii@163.com.
authors.forename: Manhua
authors.initials: M
authors.lastname: Lv
authors.affiliation: Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: Sulinxi2009@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000209:etiology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology*
chemical_list: D018696:Neuroprotective Agents; D005677:G(M1) Ganglioside
keywords: Apoptosis; Brain; Endoplasmic reticulum stress; Ischemia/reperfusion injury; Monosialotetrahexosy-1 ganglioside