Adult responses to an ischemic stroke in a rat model of neonatal stress and morphine treatment.

Adult responses to an ischemic stroke in a rat model of neonatal stress and morphine treatment.
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在新生儿应激和吗啡治疗的大鼠模型中,成人对缺血性中风的反应。

DOI:
10.1016/j.ijdevneu.2012.09.003
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发表时间:
2013-02
期刊:
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
影响因子:
--
通讯作者:
Gleason CA
Gleason CA
中科院分区:
其他
文献类型:
--
作者:
Hays SL;Valieva OA;McPherson RJ;Juul SE;Gleason CA

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危重新生儿经历的压力可能会改变大脑发育。通过啮齿类动物模型,我们之前发现,新生儿应激、吗啡和应激加吗啡治疗都会影响早期基因表达,并可能损害神经发育和学习行为。我们假设新生儿应激与吗啡的结合可能改变新生儿血管生成和/或成人脑血管密度,从而增加成人脑缺血后的损伤。为了验证这一点,新生Lewis大鼠在出生后第3天至第7天进行了8小时/天的母鼠分离,加上上午/下午的缺氧暴露和生理盐水或吗啡治疗(2 mg/kg s.c)。一部分患者接受溴脱氧尿苷治疗以追踪血管生成。​为了研究脑损伤易感性,我们在出生后80天对成年大鼠进行了右脑中动脉闭塞术(MCAO),造成单侧脑缺血病变。损伤后48小时取出脑组织进行组织学处理。采用苏木精、伊红组织学评价及银染色评价脑损伤程度。与我们的假设相反,新生儿吗啡、应激或两者结合都不会影响脑血管密度或mcao诱导的脑损伤。成年大鼠未检测到新生血管生成,可能是由于内皮细胞的周转。虽然与血管生成无关,但海马颗粒细胞神经发生被检测到,并且在经历新生儿应激的大鼠中有增加溴脱氧尿苷掺入的趋势(P = 0.073)。这些发现与吗啡对脑血管功能的影响以及吗啡对海马神经发生的急性影响的其他数据进行了对比。
Critically ill newborn infants experience stressors that may alter brain development. Using a rodent model, we previously showed that neonatal stress, morphine, and stress plus morphine treatments each influence early gene expression and may impair neurodevelopment and learning behavior. We hypothesized that the combination of neonatal stress with morphine may alter neonatal angiogenesis and/or adult cerebral blood vessel density and thus increase injury after cerebral ischemia in adulthood. To test this, neonatal Lewis rats underwent 8 h/d maternal separation, plus morning/afternoon hypoxia exposure and either saline or morphine treatment (2 mg/kg s.c.) from postnatal day 3 to 7. A subset received bromodeoxyuridine to track angiogenesis. Adult brains were stained with collagen IV to quantify cerebral blood vessel density. To examine vulnerability to brain injury, postnatal day 80 adult rats underwent right middle cerebral artery occlusion (MCAO) to produce unilateral ischemic lesions. Brains were removed and processed for histology 48 hours after injury. Brain injury was assessed by histological evaluation of hematoxylin and eosin, and silver staining. In contrast to our hypothesis, neither neonatal morphine, stress, nor the combination affected cerebral vessel density or MCAO-induced brain injury. Neonatal angiogenesis was not detected in adult rats possibly due to turnover of endothelial cells. Although unrelated to angiogenesis, hippocampal granule cell neurogenesis was detected and there was a trend (P = 0.073) toward increased bromodeoxyuridine incorporation in rats that underwent neonatal stress. These findings are discussed in contrast to other data concerning the effects of morphine on cerebrovascular function, and acute effects of morphine on hippocampal neurogenesis.
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