Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat

Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat
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DOI:
10.1016/j.brainresbull.2005.11.011
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发表时间:
2006-03-31
影响因子:
3.8
通讯作者:
LeBlanc, MH
LeBlanc, MH
中科院分区:
医学3区
文献类型:
--
作者:
Feng, YZ;Paul, IA;LeBlanc, MH

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烟酰胺减轻成年大鼠缺血性脑损伤。在新生动物身上能看到类似的大脑保护吗?将7日龄大鼠幼仔的右颈动脉永久性结扎,随后给予2.5小时的8%氧气。复氧后5 min,i. p.给予烟酰胺250或500 mg/kg,第二次给药在第一次给药后6 h。缺氧22天后,通过右半球重量减少来评估脑损伤。烟酰胺500 mg/kg可使脑重量减轻从溶剂组幼仔(n = 28)的24.6 +/- 3.6%降至给药组幼仔的11.9 +/- 2.6%(n = 29,P < 0.01),但250 mg/kg给药不影响脑重量。烟酰胺500 mg/kg也改善了转棒性能。在复氧后16小时,通过酶免疫测定法在皮质中测量的8-异前列腺素F-2 α的水平在假处理组(n = 6)中为115 +/- 7 pg/g,在500 mg/kg烟酰胺处理组(n = 7)中为175 17 pg/g,在溶媒处理组中为320 79 pg/g(n = 7,相对于假手术P <0.05,相对于烟酰胺P < 0.05)。烟酰胺可降低缺氧缺血引起的caspase-3活性升高(P < 0.01)。烟酰胺可能通过降低氧化应激和caspase-3活性来减轻新生大鼠的脑损伤。(c)2005年爱思唯尔公司All rights reserved.
Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the fight hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 +/- 3.6% in vehicle pups (n = 28) to 11.9 +/- 2.6% in the treated pups (it = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F-2 alpha measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 +/- 7 pg/g in the shams (n = 6), 175 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity. (c) 2005 Elsevier Inc. All rights reserved.