Teo Jonathan D, Morris Margaret J, Jones Nicole M
Department of Pharmacology, School of Medical Sciences, UNSW Sydney, New South Wales, 2052, Australia.
Department of Pharmacology, School of Medical Sciences, UNSW Sydney, New South Wales, 2052, Australia.
Behav Brain Res. 2017 Aug 30;333:27-34. doi: 10.1016/j.bbr.2017.06.036. Epub 2017 Jun 21.
Hypoxic-ischemic (HI) brain injury in newborns is associated with high morbidity and mortality, with many babies suffering neurological deficits. Recently, we showed that hypoxic postconditioning (PostC) immediately post injury can protect against HI up to one week in neonatal rats. Here, we aimed to examine whether long term functional deficits were also improved by PostC. Sprague-Dawley rats were assigned to control (C) or HI group on postnatal day 7 (P7). The HI group underwent unilateral carotid artery occlusion followed by hypoxia (7% oxygen, 3h). Half of each group were randomly assigned to the PostC group (8% oxygen, 1h/day for 5days post-injury), or normoxic group, where animals were kept under ambient conditions. Righting reflex and negative geotaxis tests were performed on P8 and P14. On P42, rats underwent further behavioural tests of motor function and memory (forelimb grip strength, grid walking and novel object recognition tasks). Brain injury was assessed using histological scoring of brain sections. At P14, PostC reduced the righting reflex deficit compared to HI alone. Long-term (6 weeks) behavioural deficits were observed in grid walking and novel object recognition tests after HI alone, with both functions improved following PostC. Following HI, there was an increase in brain injury assessed by histological scoring compared to control, and this damage was reduced by PostC. This novel finding of long-term histological neuroprotection accompanied by functional improvements by PostC further demonstrates the clinical potential of mild hypoxia for the treatment of HI brain injury.
新生儿缺氧缺血性（HI）脑损伤与高发病率和死亡率相关，许多婴儿患有神经功能缺损。最近，我们发现损伤后立即进行缺氧后处理（PostC）可在新生大鼠中对HI起到长达一周的保护作用。在此，我们旨在研究PostC是否也能改善长期功能缺损。将出生后第7天（P7）的Sprague-Dawley大鼠分为对照组（C）或HI组。HI组先进行单侧颈动脉闭塞，然后进行缺氧处理（7%氧气，3小时）。每组中的一半随机分配到PostC组（8%氧气，损伤后每天1小时，共5天）或常氧组，常氧组动物饲养在环境条件下。在P8和P14进行翻正反射和负趋地性测试。在P42，对大鼠进行运动功能和记忆的进一步行为测试（前肢握力、网格行走和新物体识别任务）。使用脑切片的组织学评分评估脑损伤。在P14时，与单纯HI相比，PostC减轻了翻正反射缺损。单纯HI后，在网格行走和新物体识别测试中观察到长期（6周）行为缺损，PostC后这两种功能均得到改善。与对照组相比，HI后通过组织学评分评估的脑损伤增加，而PostC减轻了这种损伤。PostC带来长期组织学神经保护并伴有功能改善这一新发现进一步证明了轻度缺氧治疗HI脑损伤的临床潜力。
