title: Relationship between cerebral sodium-glucose transporter and hyperglycemia in cerebral ischemia.
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 6h 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 6h 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.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Harada
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan. Electronic address: stoku@pharm.kobegakuin.ac.jp.
authors.forename: Shogo
authors.initials: S
authors.lastname: Tokuyama
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009474:Neurons / Q000473:pathology; D010695:Phlorhizin / Q000494:pharmacology; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
chemical_list: D051247:Sodium-Glucose Transport Proteins; D006861:Hydrogen Peroxide; D010695:Phlorhizin
keywords: Cerebral stroke; Focal cerebral ischemia; Hyperglycemia; Primary cortical neuron; Sodium–glucose transporter