Effects of a single dose of erythropoietin on subsequent seizure susceptibility in rats exposed to acute hypoxia at P10
Effects of a single dose of erythropoietin on subsequent seizure susceptibility in rats exposed to acute hypoxia at P10
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DOI：
10.1111/j.1528-1167.2006.00900.x
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发表时间：
2007-01-01
期刊：
影响因子：
5.6
通讯作者：
El Sabban, Marwan E.
中科院分区：
文献类型：
--
作者：
Mikati, Mohamad A.;El Hokayem, Jimmy A.;El Sabban, Marwan E.
目的：目的：探讨促红细胞生成素（EPO）对急性缺氧后10天（P10）大鼠癫痫发作相关神经元损伤的保护作用。方法：将4组大鼠在P10处理后，分别给予海人酸（KA）10 mg/kg，i. p. P29：缺氧-NS-KA组（n = 11）：急性缺氧（降至4%O2）后立即腹腔注射生理盐水;缺氧-EPO-KA组（n = 10）：急性缺氧后立即腹腔注射EPO（1,000 U/Kg）。常氧-NS-KA组（n = 11）：假手术后腹腔注射生理盐水。常氧-EPO-KA组（n = 10）：假手术后立即腹腔注射EPO（1000 U/Kg）。在P29接受KA后，使用录像带技术监测所有大鼠，并在P31处死。TUNEL和Hoechst染色以评估细胞凋亡，并进行常规组织学检查以计数海马细胞。在P10急性缺氧事件后直接给予单剂量促红细胞生成素导致P29前肢阵挛发作的潜伏期增加，这些发作的持续时间缩短，防止海马细胞损失，缺氧-EPO-KA组海马细胞凋亡明显低于缺氧-NS-KA组。这些数据支持促红细胞生成素对长时间免疫缺陷的有利保护作用。急性缺氧在发育中的大脑中的长期后果，并提高了其作为人类新生儿缺氧性脑病后潜在神经保护剂研究的可能性。
Purpose: To determine if posthypoxia treatment with erythropoietin (EPO) has protective effects against subsequent susceptibility to seizure related neuronal injury in rat pups subjected to acute hypoxia at P10.Methods: Four groups of rats were manipulated at P10, as described below, then all received kainic acid (KA) (10 mg/kg i.p.) at P29: Hypoxia-NS-KA group (n = 11): subjected to acute hypoxia (down to 4% O2), and then immediately received saline i.p. Hypoxia-EPO-KA group (n = 10): subjected to acute hypoxia and then immediately received EPO (1,000 U/Kg i.p.). Normoxia-NS-KA group (n = 11): sham manipulated and injected with saline. Normoxia-EPO-KA group (n = 10): sham manipulated then immediately injected with EPO (1000 U/Kg i.p.). After receiving KA at P29, all rats were monitored using videotape techniques, and were sacrificed at P31. TUNEL and Hoechst stains to assess for apoptosis, and regular histology for hippocampal cell counts were performed.Results: Administration of the single dose of erythropoietin directly after an acute hypoxic event at P10 resulted at P29 in increased latency to forelimb clonus seizures, reduced duration of these seizures, protection against hippocampal cell loss, and decreased hippocampal apoptosis in the Hypoxia-EPO-KA group as compared to the Hypoxia-NS-KA group.Conclusion: These data support the presence of favorable protective effects of erythropoietin against the long-term consequences of acute hypoxia in the developing brain and raise the possibility of its investigation as a potential neuroprotective agent after human neonatal hypoxic encephalopathy.