Nicotine Exacerbates Brain Edema during In Vitro and In Vivo Focal Ischemic Conditions
Nicotine Exacerbates Brain Edema during In Vitro and In Vivo Focal Ischemic Conditions
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DOI：
10.1124/jpet.109.157776
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发表时间：
2010-02-01
影响因子：
3.5
通讯作者：
Abbruscato, Thomas J.
中科院分区：
文献类型：
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作者：
Paulson, Jennifer R.;Yang, Tianzhi;Abbruscato, Thomas J.
我们之前已经证明尼古丁，烟草制品的成瘾成分，在体外缺氧-血糖暴露时改变血脑屏障（BBB） Na+, K+, 2Cl（-）共转运蛋白（NKCC）。腹腔NKCC的衰减表明，在缺氧-血糖或中风情况下，脑细胞外液中离子的积累会导致脑液体或细胞毒性水肿的增加。为了进一步研究尼古丁产品是否有可能通过增加脑水肿形成而恶化脑卒中结局，我们使用了两个独立的模型来模拟脑卒中情况，以解释短期和长期服用尼古丁产品对脑卒中后脑水肿的影响。研究了短期或长期暴露于尼古丁和香烟烟雾成分的大鼠海马切片的氧葡萄糖剥夺（OGD）。在短期暴露期间，模拟重度吸烟者浓度的尼古丁的存在增加了OGD期间海马切片的含水量。此外，长期给药1周的尼古丁增加了海马切片的含水量，而尼古丁乙酰胆碱受体（nAChR）拮抗剂可以减弱这种含水量，这表明尼古丁通过nAChR增加了OGD期间的水肿。第二种局灶性缺血模型，即大脑中动脉闭塞，与生理盐水对照组相比，在短期暴露于尼古丁期间，梗死面积增加，在短期和长期服用尼古丁期间，水肿增加。这些发现支持尼古丁产品不仅增加中风的发病率，而且有可能通过增加水肿形成而恶化中风结果的范式。
We have previously shown that nicotine, the addictive component of tobacco products, alters the blood-brain barrier (BBB) Na+, K+, 2Cl(-) cotransporter (NKCC) during in vitro hypoxia-aglycemia exposure. Attenuation of abluminal NKCC suggests that accumulation of ions in the brain extracellular fluid would result in an increase of fluid or cytotoxic edema in the brain during hypoxia-aglycemia or stroke conditions. To further investigate whether nicotine products have the potential to worsen stroke outcome by increasing edema formation, two separate models to mimic stroke conditions were utilized to decipher the effects of short-term and long-term administrations of nicotine products on brain edema following stroke. Oxygen glucose deprivation (OGD) was studied in rat hippocampal slices with short-term or long-term exposure to nicotine and cigarette smoke constituents. During short-term exposure, the presence of nicotine at a concentration mimicking heavy smokers increased water content of hippocampal slices during OGD. Furthermore, long-term 1-week administration of nicotine increased water content in hippocampal slices that could be attenuated with nicotine acetylcholine receptor (nAChR) antagonists, suggesting nicotine increase edema during OGD via nAChRs. A second model of focal ischemia, middle cerebral artery occlusion, showed an increase of infarct size during short-term exposure to nicotine and an increase of edema during both short-term and long-term administration of nicotine, compared with saline controls. These findings support the paradigm that nicotine products not only increase the incidence of stroke but also have the potential to worsen stroke outcome by increased edema formation.