UMR 7289, CNRS, Aix-Marseille Université, institut de neurosciences de la Timone, 13385 Marseille, France.
UMR 7289, CNRS, Aix-Marseille Université, institut de neurosciences de la Timone, 13385 Marseille, France.
Ann Phys Rehabil Med. 2020 Oct;63(5):422-430. doi: 10.1016/j.rehab.2019.10.002. Epub 2019 Nov 19.
Cerebral palsy (CP) is a complex syndrome of various sensory, motor and cognitive deficits. Its prevalence has recently decreased in some developed countries and its symptoms have also shifted since the 1960s. From the 1990s, CP has been associated with prematurity, but recent epidemiologic studies show reduced or absent brain damage, which recapitulates developmental coordination disorder (DCD). In previous studies, we developed a rat model based on mild intrauterine hypoperfusion (MIUH) that recapitulated the diversity of symptoms observed in preterm survivors. Briefly, MIUH led to early inflammatory processes, diffuse brain damage, minor locomotor deficits, musculoskeletal pathologies, neuroanatomical and functional disorganization of the primary somatosensory (S1) cortex but not in the motor cortex (M1), delayed sensorimotor reflexes, spontaneous hyperactivity, deficits in sensory information processing, and memory and learning impairments in adult rats. Adult MIUH rats also exhibited changes in muscle contractile properties and phenotype, enduring hyperreflexia and spasticity, as well as hyperexcitability in the sensorimotor cortex. We recently developed a rat model of DCD based on postnatal sensorimotor restriction (SMR) without brain damage. Briefly, SMR led to digitigrade locomotion (i.e., "toe walking") related to ankle-knee overextension, degraded musculoskeletal tissues (e.g., gastrocnemius atrophy), and lumbar hyperreflexia. The postnatal SMR then led to secondary degradation of the hind-limb maps in S1 and M1 cortices, altered cortical response properties and cortical hyperexcitability, but no brain damage. Thus, our 2 rat models appear to recapitulate the diversity of symptoms ranging from CP to DCD and contribute to understanding the emergence and mechanisms underlying the corresponding neurodevelopmental disorders. These preclinical models seem promising for testing strategies of rehabilitation based on both physical and cognitive training to promote adaptive brain plasticity and to improve physical body conditions.
脑瘫（CP）是一种复杂的综合征，涉及各种感觉、运动和认知缺陷。近年来，一些发达国家脑瘫的发病率有所下降，其症状自 20 世纪 60 年代以来也有所转变。从 20 世纪 90 年代开始，脑瘫与早产有关，但最近的流行病学研究表明，脑损伤减少或不存在，这与发育性协调障碍（DCD）相符。在之前的研究中，我们建立了一种基于轻度宫内低灌注（MIUH）的大鼠模型，该模型再现了早产儿存活者中观察到的各种症状。简而言之，MIUH 导致了早期炎症过程、弥漫性脑损伤、轻微运动缺陷、肌肉骨骼病理学、初级体感（S1）皮层的神经解剖和功能紊乱，但运动皮层（M1）没有、感觉运动反射延迟、自发性过度活动、感觉信息处理缺陷以及成年大鼠的学习记忆障碍。成年 MIHU 大鼠还表现出肌肉收缩特性和表型的变化，持续出现反射亢进和痉挛，以及感觉运动皮层的过度兴奋。我们最近建立了一种基于产后感觉运动限制（SMR）而无脑损伤的 DCD 大鼠模型。简而言之，SMR 导致了与踝关节-膝关节过度伸展相关的趾行运动（即“足尖行走”）、肌肉骨骼组织退化（例如，腓肠肌萎缩）和腰部反射亢进。随后，产后 SMR 导致 S1 和 M1 皮层的后肢图的继发性退化，改变了皮质反应特性和皮质过度兴奋，但没有脑损伤。因此，我们的 2 种大鼠模型似乎再现了从脑瘫到 DCD 的各种症状，并有助于理解相应的神经发育障碍的出现和机制。这些临床前模型似乎有望用于测试基于身体和认知训练的康复策略，以促进适应性大脑可塑性并改善身体状况。
