Sodium influx through cerebral sodium-glucose transporter type 1 exacerbates the development of cerebral ischemic neuronal damage.

Sodium influx through cerebral sodium-glucose transporter type 1 exacerbates the development of cerebral ischemic neuronal damage. Eur J Pharmacol. 2017 Feb 04;: Authors: Yamazaki Y, Harada S, Wada T, Hagiwara T, Yoshida S, Tokuyama S Abstract We recently reported that cerebral sodium-glucose transporter type 1 (SGLT-1) plays a role in exacerbation of cerebral ischemia. However, the mechanism by which cerebral SGLT-1 acts remains unclear. Here we demonstrated that sodium influx through cerebral SGLT-1 exacerbates cerebral ischemic neuronal damage. SGLT-specific sodium ion influx was induced using α-methyl-D-glucopyranoside (α-MG). Intracellular sodium concentrations in primary cortical neurons were estimated using sodium-binding benzofuran isophthalate fluorescence. SGLT-1 knockdown in primary cortical neurons and mice was achieved using SGLT-1 siRNA. The survival rates of primary cultured cortical neurons were assessed using biochemical assays 1day after treatment. Middle cerebral artery occlusion (MCAO) was used to generate a focal cerebral ischemic model in SGLT-1 knockdown mice. The change in fasting blood glucose levels, infarction development, and behavioral abnormalities were assessed 1day after MCAO. Treatment with 200mM α-MG induced a continuous increase in the intracellular sodium concentration, and this increase was normalized after α-MG removal. Neuronal SGLT-1 knockdown had no effect on 100µM H2O2-induced neuronal c...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research