کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2534512 1559093 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Long-term treatment with nicotine suppresses neurotoxicity of, and microglial activation by, thrombin in cortico-striatal slice cultures
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Long-term treatment with nicotine suppresses neurotoxicity of, and microglial activation by, thrombin in cortico-striatal slice cultures
چکیده انگلیسی

The mechanisms of tissue injury associated with intracerebral hemorrhage involve multiple actions of thrombin, a blood-derived coagulation factor, on cells within the brain parenchyma, including activation of microglia as well as direct cytotoxicity on neurons. Based on emerging evidence that stimulation of nicotinic acetylcholine receptors provides neuroprotective effects and also suppresses cytotoxic properties of activated microglia, we investigated the effect of nicotine on thrombin-induced pathological changes in cortico-striatal slice cultures. Long-term (15 days), but not short-term (up to 144 h), treatment with nicotine (3–30 μM) partially prevented thrombin-induced neuron loss in the cortical region and tissue shrinkage in the striatal region. In addition, long-term treatment with nicotine suppressed thrombin-induced increase in microglia in a concentration-dependent manner, which was accompanied by suppression of morphological changes of microglia into their activated form. Methyllycaconitine (an α7-selective antagonist) and dihydro-β-erythroidine (an antagonist specific for β2-containing receptors), as well as mecamylamine (a non subtype-selective nicotinic receptor antagonist), abrogated the protective effect of nicotine against thrombin-induced striatal shrinkage and the inhibitory effect of nicotine against thrombin-induced increase in activated microglia. Besides adding further evidence that nicotinic receptor stimulation exerts neuroprotective functions, these results reveal a novel mode of action of nicotine on neural tissues that appears after long-term treatment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 602, Issues 2–3, 14 January 2009, Pages 288–293
نویسندگان
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