The accumulation of brain water-free sodium is associated with ischemic damage independent of the blood pressure in female rats
| Autor: | Kenji Yagi, Junichiro Satomi, Keiko T. Kitazato, Manabu Sumiyoshi, Takeshi Miyamoto, Tomoya Kinouchi, Kazuyuki Kuwayama, Shinji Nagahiro, Nobuhisa Matsushita, Yoshitaka Kurashiki |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
endocrine system Normal diet medicine.drug_class Ovariectomy Mineralocorticoid receptor Neuroscience(all) Ischemia Clinical Neurology Blood Pressure High-salt intake Brain water-free sodium accumulation Internal medicine medicine Animals RNA Messenger Na+/K+-ATPase Rats Wistar Molecular Biology Analysis of Variance Chemistry General Neuroscience Sodium Antagonist Brain Water Infarction Middle Cerebral Artery Cerebral ischemia medicine.disease Eplerenone Rats Disease Models Animal Endocrinology Receptors Mineralocorticoid Gene Expression Regulation Estrogen Hypertension Ovariectomized rat Female Neurology (clinical) Sodium-Potassium-Exchanging ATPase hormones hormone substitutes and hormone antagonists medicine.drug Developmental Biology |
| Zdroj: | Brain Research. 1616:37-44 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2015.04.051 |
| Popis: | Estrogen deficiency worsens ischemic stroke outcomes. In ovariectomized (OVX(+)) rats fed a high-salt diet (HSD), an increase in the body Na(+)/water ratio, which characterizes water-free Na(+) accumulation, was associated with detrimental vascular effects independent of the blood pressure (BP). We hypothesized that an increase in brain water-free Na(+) accumulation is associated with ischemic brain damage in OVX(+)/HSD rats. To test our hypothesis we divided female Wistar rats into 4 groups, OVX(+) and OVX(-) rats fed HSD or a normal diet (ND), and subjected them to transient cerebral ischemia. The brain Na(+)/water ratio was increased even in OVX(+)/ND rats and augmented in OVX(+)/HSD rats. The increase in the brain Na(+)/water ratio was positively correlated with expansion of the cortical infarct volume without affecting the BP. Interestingly, OVX(+) was associated with the decreased expression of ATP1α3, a subtype of the Na(+) efflux pump. HSD increased the expression of brain Na(+) influx-related molecules and the mineralocorticoid receptor (MR). The pretreatment of OVX(+)/HSD rats with the MR antagonist eplerenone reduced brain water-free Na(+) accumulation, up-regulated ATP1α3, down-regulated MR, and reduced the cortical infarct volume. Our findings show that the increase in the brain Na(+)/water ratio elicited by estrogen deficiency or HSD is associated with ischemic brain damage BP-independently, suggesting the importance of regulating the accumulation of brain water-free Na(+). The up-regulation of ATP1α3 and the down-regulation of MR may provide a promising therapeutic strategy to attenuate ischemic brain damage in postmenopausal women. |
| Databáze: | OpenAIRE |
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