Impact of neonatal asphyxia and hind limb immobilization on musculoskeletal tissues and S1 map organization: implications for cerebral palsy.
Cerebral palsy (CP) is a complex disorder of locomotion, posture and movements resulting from pre-, peri- or postnatal damage to the developing brain. In a previous study (Strata, F., Coq, J.O., Byl, N.N., Merzenich, M.M., 2004. Comparison between sensorimotor restriction and anoxia on gait and motor cortex organization: implications for a rodent model of cerebral palsy. Neuroscience 129, 141-156.), CP-like movement disorders were more reliably reproduced in rats by hind limb sensorimotor restriction (disuse) during development rather than perinatal asphyxia (PA). To gain new insights into the underpinning mechanisms of CP symptoms we investigated the long-term effects of PA and disuse on the hind limb musculoskeletal histology and topographical organization in the primary somatosensory cortex (S1) of adult rats. Developmental disuse (i.e. hind limb immobilization) associated with PA induced muscle fiber atrophy, extracellular matrix changes in the muscle, and mild to moderate ankle and knee joint degeneration at levels greater than disuse alone. Sensorimotor restricted rats with or without PA exhibited a topographical disorganization of the S1 cortical hind limb representation with abnormally large, multiple and overlapping receptive fields. This disorganization was enhanced when disuse and PA were associated. Altered cortical neuronal properties included increased cortical responsiveness and a decrease in neuronal selectivity to afferent inputs. These data support previous observations that asphyxia per se can generate the substrate for peripheral tissue and brain damage, which are worsened by aberrant sensorimotor experience during maturation, and could explain the disabling movement disorders observed in children with CP.
UMR 6149 Neurobiologie Intégrative et Adaptative, Aix-Marseille Université-CNRS, Pôle 3C, Case B, 3 Place Victor Hugo, Marseille Cedex 03, France. coqjo@up.univ-mrs.fr
Jacques-Olivier
JO
Coq
Fabrizio
F
Strata
Michaël
M
Russier
Fayez F
FF
Safadi
Michael M
MM
Merzenich
Nancy N
NN
Byl
Mary F
MF
Barbe
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000503:physiopathology*; D001931:Brain Mapping; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002547:Cerebral Palsy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D055513:Connective Tissue Growth Factor; D004195:Disease Models, Animal; D005260:Female; D006614:Hindlimb / Q000254:growth & development / Q000473:pathology; D019417:Hindlimb Suspension; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000254:growth & development / Q000473:pathology* / Q000503:physiopathology; D009139:Musculoskeletal Abnormalities / Q000209:etiology / Q000473:pathology*; D009210:Myofibrils / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000473:pathology / Q000503:physiopathology
C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor