Relationship between cerebral sodium–glucose transporter and hyperglycemia in cerebral ischemia. (14th September 2015)

• Record Type: Journal Article
• Authors: Yamazaki, Yui; Harada, Shinichi; Tokuyama, Shogo
• Is Part Of: Neuroscience letters. Volume 604(2015)
• Page Start: 134
• Page End: 139
• Publication Date: 2015-09-14
• Subjects: FBG fasting blood glucose -- SGLT sodium–glucose transporter -- PHZ phlorizin -- DIV day in vitro -- H2O2 hydrogen peroxide -- α-MG alpha-d-methylglucoside -- WST-8 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium -- MCAO middle cerebral artery occlusion -- i.c.v. intracerebroventricular -- TTC 2, 3, 5-triphenyltetrazolium chloride -- NDS neurological deficit score -- ANOVA one-way analysis of variance; Sodium–glucose transporter -- Cerebral stroke -- Hyperglycemia -- Primary cortical neuron -- Focal cerebral ischemia; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2015.08.004
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Cerebral SGLT had no effect on hydrogen peroxide alone-induced cell death. Additional glucose treatment exacerbates H2 O2 -induced neuronal cell death. Cerebral SGLT involves in neuronal cell death under hyperglycemic condition. Suppression of cerebral SGLT in hyperglycemic condition improve neuronal damage. Cerebral SGLTs respond to post-ischemic hyperglycemia and exacerbate neuronal damage. Abstract: Post-ischemic hyperglycemia exacerbates the development of cerebral ischemia. To elucidate this exacerbation mechanism, we focused on sodium–glucose transporter (SGLT) as a mediator that lead hyperglycemia to cerebral ischemia. SGLT transport glucose into the cell, together with sodium ion, using the sodium concentration gradient. We have previously reported that suppression of cerebral SGLT ameliorates cerebral ischemic neuronal damage. However, detail relationship cerebral between SGLT and post-ischemic hyperglycemia remain incompletely defined. Therefore, we examined the involvement of cerebral SGLT on cerebral ischemic neuronal damage with or without hyperglycemic condition. Cell survival rate of primary cultured neurons was assessed by biochemical assay. A mouse model of focal ischemia was generated using a middle cerebral artery occlusion (MCAO). Neuronal damage was assessed with histological and behavioral analyses. Concomitant hydrogen peroxide/glucose treatment exacerbated hydrogen peroxide alone-induced cell death. Although a SGLT family-specific inhibitor, phlorizin had no effect on developed hydrogen peroxide alone-induced cell death, it suppressed cell death induced by concomitant hydrogen peroxide/glucose treatment. α-MG induced a concentration-dependent and significant decrease in neuronal survival. PHZ administered on immediately after reperfusion had no effect, but PHZ given at 6 h after reperfusion had an effect. Our in vitro study indicates that SGLT is not involved in neuronal cell death in non-hyperglycemic condition. We have already reported that post-ischemic hyperglycemia begins to develop at 6 h after MCAO. Therefore, current our in vivo study show post-ischemic hyperglycemic condition may be necessary for the SGLT-mediated exacerbation of cerebral ischemic neuronal damage.