Rumajogee Prakasham, Bregman Tatiana, Miller Steven P, Yager Jerome Y, Fehlings Michael G
Division of Genetics and Development, Krembil Research Institute, Toronto Western Hospital, University Health Network , Toronto, ON , Canada.
Department of Pediatrics, Hospital for Sick Children , Toronto, ON , Canada.
Front Neurol. 2016 Apr 25;7:57. doi: 10.3389/fneur.2016.00057. eCollection 2016.
Cerebral palsy (CP) is a complex multifactorial disorder, affecting approximately 2.5-3/1000 live term births, and up to 22/1000 prematurely born babies. CP results from injury to the developing brain incurred before, during, or after birth. The most common form of this condition, spastic CP, is primarily associated with injury to the cerebral cortex and subcortical white matter as well as the deep gray matter. The major etiological factors of spastic CP are hypoxia/ischemia (HI), occurring during the last third of pregnancy and around birth age. In addition, inflammation has been found to be an important factor contributing to brain injury, especially in term infants. Other factors, including genetics, are gaining importance. The classic Rice-Vannucci HI model (in which 7-day-old rat pups undergo unilateral ligation of the common carotid artery followed by exposure to 8% oxygen hypoxic air) is a model of neonatal stroke that has greatly contributed to CP research. In this model, brain damage resembles that observed in severe CP cases. This model, and its numerous adaptations, allows one to finely tune the injury parameters to mimic, and therefore study, many of the pathophysiological processes and conditions observed in human patients. Investigators can recreate the HI and inflammation, which cause brain damage and subsequent motor and cognitive deficits. This model further enables the examination of potential approaches to achieve neural repair and regeneration. In the present review, we compare and discuss the advantages, limitations, and the translational value for CP research of HI models of perinatal brain injury.
脑瘫（CP）是一种复杂的多因素疾病，影响约2.5 - 3‰的足月活产婴儿，早产婴儿中这一比例高达22‰。脑瘫是由出生前、出生时或出生后发育中的大脑受到损伤所致。这种疾病最常见的形式，即痉挛型脑瘫，主要与大脑皮层、皮层下白质以及深部灰质的损伤有关。痉挛型脑瘫的主要病因是缺氧缺血（HI），发生在妊娠晚期和出生前后。此外，炎症已被发现是导致脑损伤的一个重要因素，尤其是在足月儿中。其他因素，包括遗传因素，也越来越受到重视。经典的赖斯 - 万努奇缺氧缺血模型（7日龄大鼠幼崽单侧结扎颈总动脉，随后暴露于8%氧气的低氧空气中）是一种新生儿中风模型，对脑瘫研究有很大贡献。在这个模型中，脑损伤类似于在严重脑瘫病例中观察到的情况。这个模型及其众多变体使人们能够精细调整损伤参数，以模拟并因此研究人类患者中观察到的许多病理生理过程和情况。研究人员可以重现导致脑损伤以及随后运动和认知缺陷的缺氧缺血和炎症。这个模型还能进一步检验实现神经修复和再生的潜在方法。在本综述中，我们比较并讨论围产期脑损伤缺氧缺血模型对脑瘫研究的优势、局限性及转化价值。
