Clinical commentaryMonosialotetrahexosy-1 ganglioside attenuates diabetes-associated cerebral ischemia/reperfusion injury through suppression of the endoplasmic reticulum stress-induced apoptosis

- Cerebral ischemia was established by MCAO in diabetic rats.
- GM1 significantly decreased cerebral infarct size and improved neurological behavior.
- GM1 dramatically reduced TUNEL-positive cell numbers in the cerebral cortex.
- GM1 increased GRP78 and reduced CHOP/GADD153 expression.
- GM1 activated caspase-12 in ischemic brain tissue.

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 (15 mg/kg) at 20 min 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.