Department of Pediatrics, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada.
Centre national de référence de l'AVC de l'enfant, CIC1408, CHU Saint-Étienne, INSERM, Saint-Étienne, France.
Int J Dev Neurosci. 2020 Jun;80(4):257-266. doi: 10.1002/jdn.10022. Epub 2020 Mar 24.
There is currently no targeted treatment available for neonatal arterial ischemic strokes (NAIS). Epidemiological studies demonstrated that perinatal infection/inflammation, peripartum hypoxia, and occlusion of the internal carotid tree are the main determinants of NAIS. The well-established benefit of therapeutic hypothermia (HT) in neonatal encephalopathy due to diffuse hypoxia-ischemia provides a rationale for the potential use of HT as a neuroprotective strategy in NAIS.
We used a rat model to reproduce the most prevalent human physiopathological scenario of NAIS. The neuroprotective effect of HT was measured by morphometric magnetic resonance imaging, [ F] fluorodeoxyglucose (FDG) metabolic activity by positron emission tomography/computed tomography, and behavioral tests.
HT (a) prevented the occurrence of 44% of NAIS, (b) reduced the volume of strokes by 37%, (c) enhanced [ F] FDG metabolic activity within the territory of the occluded carotid artery, and (d) improved motor behavior. Both morphometric and metabolic techniques showed consistently that HT provided a neuroprotective effect located in the motor cortex, hippocampus, and caudate-putamen.
Through combining anatomical, metabolic imaging, and behavioral studies, our study provides evidence of neuroprotective effects of HT in NAIS. These results are potentially translational to human NAIS.
目前,新生儿动脉缺血性脑卒中(NAIS)尚无针对性的治疗方法。流行病学研究表明,围产期感染/炎症、围生期缺氧和颈内动脉树阻塞是导致 NAIS 的主要决定因素。广泛缺氧缺血性新生儿脑病中治疗性低温(HT)已被证实具有益处,这为 HT 作为 NAIS 的神经保护策略的潜在应用提供了依据。
我们使用大鼠模型再现了最常见的人类 NAIS 病理生理场景。通过形态磁共振成像、正电子发射断层扫描/计算机断层扫描的 [ F]氟脱氧葡萄糖(FDG)代谢活性以及行为测试来衡量 HT 的神经保护作用。
HT (a)预防了 44%的 NAIS 的发生,(b)使中风体积减少了 37%,(c)增强了闭塞颈动脉区域内的 [ F]FDG 代谢活性,(d)改善了运动行为。形态和代谢技术均一致表明,HT 提供了位于运动皮层、海马体和尾状核-壳核的神经保护作用。
通过结合解剖学、代谢成像和行为研究,本研究提供了 HT 在 NAIS 中具有神经保护作用的证据。这些结果可能转化为人类 NAIS。