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Updated: Jan 3, 2026
A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy
Published on: November 3, 2016
From cerebral palsy to developmental coordination disorder: Development of preclinical rat models corresponding to
Jacques-Olivier Coq1, Marine Kochmann1, Diego C Lacerda2
1UMR 7289, CNRS, Aix-Marseille Université, institut de neurosciences de la Timone, 13385 Marseille, France.
Insights
Researchers developed two rat models to study cerebral palsy (CP) and developmental coordination disorder (DCD). These models mimic symptoms and brain changes, aiding research into neurodevelopmental disorders and rehabilitation strategies.
Area of Science:
- Neuroscience
- Developmental Biology
- Pathology
Background:
- Cerebral palsy (CP) presents diverse sensory, motor, and cognitive deficits, with evolving prevalence and symptoms.
- Recent studies link CP to prematurity but show reduced brain damage, resembling developmental coordination disorder (DCD).
- Previous work established a mild intrauterine hypoperfusion (MIUH) rat model for CP-like symptoms in preterm survivors.
Purpose of the Study:
- To present two distinct rat models recapitulating symptoms of cerebral palsy (CP) and developmental coordination disorder (DCD).
- To investigate the underlying mechanisms of these neurodevelopmental disorders.
- To establish preclinical models for testing novel rehabilitation strategies.
Main Methods:
- Mild intrauterine hypoperfusion (MIUH) model inducing inflammation, brain damage, and sensorimotor deficits.
- Postnatal sensorimotor restriction (SMR) model causing locomotion issues and musculoskeletal degradation without brain damage.
- Analysis of neuroanatomical, functional, and behavioral outcomes in adult rats.
Main Results:
- MIUH rats exhibited diffuse brain damage, cortical disorganization, delayed reflexes, hyperactivity, and learning impairments.
- SMR rats showed digitigrade locomotion, muscle atrophy, and secondary cortical map degradation without primary brain damage.
- Both models displayed sensorimotor cortex hyperexcitability and recapitulated a spectrum of CP and DCD symptoms.
Conclusions:
- The MIUH and SMR rat models effectively mimic key features of CP and DCD.
- These models offer valuable insights into the mechanisms of these neurodevelopmental disorders.
- The models are promising for evaluating rehabilitation interventions focused on plasticity and physical improvement.
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.
