کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4341388 | 1295833 | 2007 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Prevention of in vitro and in vivo acute ischemic neuronal damage by (2S)-1-(4-amino-2,3,5-trimethylphenoxy)-3-{4-[4-(4-fluorobenzyl) phenyl]-1-piperazinyl}-2-propanol dimethanesulfonate (SUN N8075), a novel neuroprotective agent with antioxidant properti
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کلمات کلیدی
PBSMCA4-HNEAc-DEVD-chorCBFMABPAmCTTC2,3,5-triphenyltetrazolium chloride - 2،3،5-trihenyltetrazolium chloride7-amino-4-methylcoumarin - 7-آمینو-4-متیل کومارینCerebral ischemia - ایسکمی مغزیterminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling - ترمینال دگزا کینوکلئوتیدیل ترانسفراز - dUTP نهایی پایان نامهTUNEL - تونلRegional cerebral blood flow - جریان خون منطقه ای مغزیmiddle cerebral artery - شریان مغزی میانیHeart rate - ضربان قلبmean arterial blood pressure - فشار خون شریانیlactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH Neuroprotection - محافظت نورونی یا محافظت از عصبPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریLipid peroxidation - پراکسیداسیون لیپید
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
(2S)-1-(4-Amino-2,3,5-trimethylphenoxy)-3-{4-[4-(4-fluorobenzyl) phenyl]-1-piperazinyl}-2-propanol dimethanesulfonate (SUN N8075) is a novel antioxidant with neuroprotective properties. We examined whether SUN N8075 inhibited the neuronal damage resulting from permanent focal cerebral ischemia, and examined its neuroprotective properties in vivo and in vitro mechanism. Focal cerebral ischemia was induced by permanent middle cerebral artery occlusion in mice, and the resulting infarction, brain swelling, and neurological deficits were evaluated after 24 h or 72 h. Brain damage was assessed histochemically using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and antibody recognizing 4-hydroxynonenal histidine adduct (4-HNE). In the in vitro study, we examined the effects of SUN N8075 on 1) lipid peroxidation in mouse brain homogenates and 2) cell viability and caspase-3 protease activity under a hypoxic insult or FeSO4 in rat cultured cerebrocortical neurons. SUN N8075 administered either 10 min before or at 1 h after the occlusion reduced both infarction size and neurological deficits. SUN N8075 reduced brain swelling when administered 10 min before, 1 h, or 3 h after occlusion. Furthermore, only pretreatment (administered 10 min before) decreased infarct volume and brain swelling at 72 h after middle cerebral artery occlusion. SUN N8075 reduced the number of TUNEL-positive cells and decreased the level of oxidative damage, as assessed by immunopositive staining to 4-HNE. SUN N8075 inhibited lipid peroxidation, leakage of lactate dehydrogenase, caspase-3 activation induced by in vitro hypoxia, and the neuronal damage induced by in vitro FeSO4 exposure. These findings indicate that SUN N8075 has neuroprotective effects against acute ischemic neuronal damage in mice and may prove promising as a therapeutic drug for stroke.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 149, Issue 4, 23 November 2007, Pages 779-788
Journal: Neuroscience - Volume 149, Issue 4, 23 November 2007, Pages 779-788
نویسندگان
Y. Kotani, N. Morimoto, Y. Oida, Y. Tamura, S. Tamura, T. Inoue, M. Shimazawa, S. Yoshimura, T. Iwama, H. Hara,