DEFEROXAMINE POSTTREATMENT REDUCES ISCHEMIC BRAIN INJURY IN NEONATAL RATS
DEFEROXAMINE POSTTREATMENT REDUCES ISCHEMIC BRAIN INJURY IN NEONATAL RATS
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DOI：
10.1161/01.str.25.5.1039
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发表时间：
1994-05-01
期刊：
影响因子：
8.3
通讯作者：
BERO, C
中科院分区：
文献类型：
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作者：
PALMER, C;ROBERTS, RL;BERO, C
背景与目的铁催化脑再灌注损伤反应性物质的形成。脑铁浓度在出生时最高，因此窒息新生儿的大脑可能会增加铁依赖性损伤的风险。我们研究了三价铁螯合剂去铁胺是否能减轻新生大鼠缺氧缺血性脑损伤。由于去铁胺具有浓度依赖性活动以外的铁螯合，我们测量脑去铁胺水平和计算去铁胺的药代动力学parameters.Methods我们产生的缺氧缺血性损伤的右大脑半球的7日龄大鼠右颈总动脉结扎，然后在8%的氧气缺氧2.25小时。在从缺氧恢复5分钟时，大鼠皮下接受100 mg/kg甲磺酸去铁胺或生理盐水。在恢复42小时时处死大鼠（生理盐水，n=33;去铁胺，n=38），通过测量半球含水量来评估早期急性水肿。其他大鼠（生理盐水，n=31;去铁胺，n=32）在30日龄时处死，用于右半球萎缩的形态测定。结果去铁胺能明显减轻大鼠右半球早期脑含水量的损伤（P
Background and Purpose Iron catalyzes the formation of damaging reactive species during cerebral reperfusion. Brain iron concentration is highest at birth, so the brain of the asphyxiated newborn may be at increased risk of iron-dependent injury. We investigated whether the ferric iron chelator deferoxamine could reduce hypoxic-ischemic brain injury in neonatal rats. Because deferoxamine has concentration-dependent activities other than iron chelation, we measured brain deferoxamine levels and calculated deferoxamine pharmacokinetic parameters.Methods We produced hypoxic-ischemic injury to the right cerebral hemisphere of 7-day-old rats by right common carotid artery ligation followed by 2.25 hours of hypoxia in 8% oxygen. At 5 minutes of recovery from hypoxia the rats received 100 mg/kg deferoxamine mesylate or saline subcutaneously. Rats (saline, n=33; deferoxamine, n=38) were killed at 42 hours of recovery to assess early acute edema by measurement of hemispheric water content. Other rats (saline, n=31; deferoxamine, n=32) were killed at 30 days of age for morphometric determination of right hemisphere atrophy. In still other rats, we measured deferoxamine levels in blood and brain after hypoxia-ischemia.Results Deferoxamine significantly reduced right hemisphere injury as measured by early water content (P