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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice
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Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice

机译：幼鱼细胞贫血小鼠脑组织缺氧的功能和解剖证

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摘要

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO(2) and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia.
机译：脑缺血是镰状细胞贫血儿童的重要性发病源;然而，伤害机制理解得很差。患有镰状细胞贫血儿童的脑血流量和低血红蛋白水平与增加的卒中风险有关，表明贫血诱导的组织缺氧可能是有助于随后发病率的重要因素。为了更好地了解脑损伤的病理生理学，脑生理学和形态学的特征在于转基因小鼠模型，节目镰状细胞模型。相对于年龄匹配的对照，镰状细胞贫血小鼠证明：（1）降低脑组织PO（2）和缺氧信号蛋白在脑皮层的大脑区域中的表达增加; （2）升高的基础脑血流动，与适应贫血诱导的组织缺氧一致; （3）脑血管血流反应性大幅降低到高额挑战; （4）颈动脉直径增加; （5）大脑中白色和灰质区域的大量变化，如前体内磁共振成像评估。这些发现支持的假设支持脑组织缺氧导致镇镰刀小鼠的适应性生理和解剖变化。这些发现可能有助于为镰状细胞贫血的儿童定义脑卒中的病理生理学。

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