Autor: |
Changbo Jin, Huishu Liu, Xinjia Han |
Rok vydání: |
2016 |
Předmět: |
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Zdroj: |
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 6:162 |
ISSN: |
2210-7789 |
DOI: |
10.1016/j.preghy.2016.08.055 |
Popis: |
Introduction Brain injury especially neuronal cell death plays an important role in the pathological process of seizure. Eclampsia is defined as the development of grand mal seizures in patients with gestational hypertension or preeclampsia. Objectives In this study we will evaluate neuronal apoptosis and the effects of α7 Nicotinic Acetylcholine Receptor Agonist Nicotine on seizure and cell death following eclampsia; then we will investigate whether α7nAChR stimulation could inhibit caspase activity via PI3K-Akt signaling. Methods C57 pregnant mice was subjected to intraperitoneal injection of pentylenetetrazole (PTZ) from gestation day (GD) 16 to GD 18 in the basis of lipopolysaccharide (LPS) administration on GD 14. Eclampsia animals received either vehicle administration, or 1 mg/kg of α7nAChR agonist nicotine, or 1 μg/kg of α7nAChR antagonist α-bungarotoxin (α-BGT) combined with nicotine. Clinical symptoms of eclampsia were evaluated; behavioral assessment of seizure severity was recorded; neuronal cell death was quantified with nissl staining and TUNEL staining. Electron microscopy was used for observing the morphological changes of neuronal apoptosis; immunofluorescence staining and Western blotting were used for the quantification and localization of activated Akt (p-Akt), and cleaved caspase-3 (CC3). Results Nicotine effectively decreased systolic blood pressure and eclampsia-like seizure severity. Electron microscopy showed that typical cell apoptotic morphology was seen in the cortex following eclampsia, nicotine significantly reduced neuronal apoptosis in the cortex. Nicotine significantly decreased CC3 levels and increased p-Akt levels in the cortex. α-Bungarotoxin reversed effects of nicotine treatment. Conclusions α7 Nicotinic Acetylcholine Receptor Agonist Nicotine improved neurological outcomes and decreased neuronal cell death in a mouse model of eclampsia. Nicotine reduced the expression of cleaved caspase-3 via the PI3K-Akt signaling pathway. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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