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From cerebral palsy to developmental coordination disorder: Development of preclinical rat models corresponding to recent epidemiological changes - 24/10/20

Doi : 10.1016/j.rehab.2019.10.002 
Jacques-Olivier Coq a, , Marine Kochmann a, Diego C. Lacerda a, b, Hanane Khalki a, c, Maxime Delcour d, Ana E. Toscano b, Florence Cayetanot a, e, Marie-Hélène Canu f, Mary F. Barbe g, Masahiro Tsuji h
a UMR 7289, CNRS, Aix-Marseille Université, institut de neurosciences de la Timone, 13385 Marseille, France 
b CAV, Department of Nursing, Federal University of Pernambuco, Vitória de Santo Antão, Brazil 
c Faculté polydisciplinaire de Beni Mellal, Mghila, Université Sultan Moulay Slimane, Beni Mellal, Morocco 
d Département de neurosciences, université de Montréal, Montréal, Canada 
e UMR_S1158 neurophysiologie respiratoire expérimentale et clinique, Sorbonne Université, Institut national de la santé et de la recherche médicale, Paris, France 
f EA 7369 - URePSSS - unité de recherche pluridisciplinaire sport santé société, université de Lille, University Artois, University Littoral Côte d’Opale, 59000 Lille, France 
g Lewis Katz School of Medicine, Temple University, 3500 North Broad Street, 19140 Philadelphia, PA, USA 
h Department of Food and Nutrition, Kyoto Women's University, 605-8501 Higashiyama-ku, Kyoto, Japan 

Corresponding author.

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Highlights

The clinical picture of cerebral palsy (CP) has greatly changed over the last decades toward encephalopathy of prematurity (EP) and recently to developmental coordination disorder (DCD).
We developed animal models of EP, based on mild intrauterine hypoperfusion, or DCD, originating from postnatal movement restriction during development.
Intrauterine hypoperfusion induced chronic inflammation that led to the emergence of neurodevelopmental disorders.
Postnatal movement restriction led to maladaptive neuroplasticity and locomotor disorders through an early atypical sensorimotor experience.
Both models share common maladaptive mechanisms of plasticity based on early, limited and atypical sensory feedback/reafference to the immature brain and self-perpetuating cycles.

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Abstract

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.

Il testo completo di questo articolo è disponibile in PDF.

Keywords : Cerebral palsy, Prematurity, Developmental Coordination Disorder, Intrauterine growth retardation, Hypoperfusion, Sensorimotor restriction, White matter injury


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Vol 63 - N° 5

P. 422-430 - ottobre 2020 Ritorno al numero
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