Aggravated brain damage after hypoxic ischemia in immature adenosine A2A knockout mice
Aggravated brain damage after hypoxic ischemia in immature adenosine A2A knockout mice
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DOI：
10.1161/01.str.0000060204.67672.8b
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发表时间：
2003-03-01
期刊：
影响因子：
8.3
通讯作者：
Fredholm, BB
中科院分区：
文献类型：
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作者：
Ådén, U;Halldner, L;Fredholm, BB
背景和目的-脑缺氧缺血（HI）是新生儿脑损伤的重要原因。腺苷被认为可以防止HI脑损伤。然而，不同腺苷受体的作用尚不清楚，特别是在幼年动物中。我们使用 7 日龄 A(2A) 基因敲除 (A2AR((-/-))) 小鼠在 HI 模型中检查了腺苷 A(2A) 受体 (A2AR) 的作用。方法 7 日龄 CD1 小鼠在左颈总动脉闭塞后暴露于 8% 氧气 30 分钟，诱导 HI。 HI 后 5 天、3 周和 3 个月，通过组织病理学评分和残余脑区测量来评估由此产生的单侧局灶性病变。 HI 后 3 周和 3 个月通过运动活动、旋转棒和平衡木行走测试对脑损伤进行行为评估。通过激光多普勒血流测定法评估皮质脑血流量，并在HI期间测量直肠温度。结果-HI期间皮质脑血流量和直肠温度的减少在野生型(A2AR((+/+)))和基因敲除小鼠之间没有差异。在A2AR((-/-))动物中，与野生型小鼠相比，脑损伤加重。与遭受 HI 的 A2AR((-/-)) 小鼠相比，遭受 HI 的 A2AR((-/-)) 小鼠在成年期表现出向前运动增加和旋转杆性能受损，而两组的横梁行走性能相似。结论-这些结果表明，与成年动物的情况相反，A2AR 在新生儿 HI 脑损伤中发挥重要的保护作用。
Background and Purpose-Cerebral hypoxic ischemia (HI) is an important cause of brain injury in the newborn infant. Adenosine is believed to protect against HI brain damage. However, the roles of the different adenosine receptors are unclear, particularly in young animals. We examined the role of adenosine A(2A) receptors (A2AR) using 7-day-old A(2A) knockout (A2AR((-/-))) mice in a model of HI.Methods-HI was induced in 7-day-old CD1 mice by exposure to 8% oxygen for 30 minutes after occlusion of the left common carotid artery. The resulting unilateral focal lesion was evaluated with the use of histopathological scoring and measurements of residual brain areas at 5 days, 3 weeks, and 3 months after HI. Behavioral evaluation of brain injury by locomotor activity, rotarod, and beam-walking test was made 3 weeks and 3 months after HI. Cortical cerebral blood flow, assessed by laser-Doppler flowmetry, and rectal temperature were measured during HI.Results-Reduction in cortical cerebral blood flow during HI and rectal temperature did not differ between wild-type (A2AR((+/+))) and knockout mice. In the A2AR((-/-)) animals, brain injury was aggravated compared with wild-type mice. The A2AR((-/-)) mice subjected to HI displayed increased forward locomotion and impaired rotarod performance in adulthood compared with A2AR((+/+)) mice subjected to HI, whereas beam-walking performance was similarly defective in both groups.Conclusions-These results suggest that, in contrast to the situation in adult animals, A2AR play an important protective role in neonatal HI brain injury.