Neuroanatomical, Sensorimotor and Cognitive Deficits in Adult Rats with White Matter Injury following Prenatal Ischemia

Authors

Maxime Delcour, Paul Olivier, Caroline Chambon, Julien Pansiot, Michaël Russier, Martine Liberge, Dong Xin, Christian Gestreau, Béatrice Alescio-Lautier, Pierre Gressens, Catherine Verney, Mary F Barbe, Olivier Baud, Jacques-Olivier Coq

Abstract

Perinatal brain injury including white matter damage (WMD) is highly related to sensory, motor or cognitive impairments in humans born prematurely. Our aim was to examine the neuroanatomical, functional and behavioral changes in adult rats that experienced prenatal ischemia (PI), thereby inducing WMD. PI was induced by unilateral uterine artery ligation at E17 in pregnant rats. We assessed performances in gait on treadmill, cognitive abilities, topographical organization of maps and numerical density of neurons and glial cells in both primary motor and somatosensory cortices, neuronal and glial density in the hippocampus and prefrontal cortex, as well as axonal degeneration and astrogliosis in white matter tracts. We found WMD in the corpus callosum and brainstem, and associated with the hippocampus and somatosensory cortex, but not the motor cortex of PI rats. PI rats exhibited mild but significant locomotor impairments that were associated with minor signs of spasticity. Motor map organization and neuronal density were normal in PI rats, contrasting with major somatosensory map disorganization, reduced neuronal density, and a marked reduction of GABAergic interneurons. PI rats exhibited spontaneous hyperactivity in open-field test and short-term memory deficits associated with abnormal neuronal density in related brain areas. Thus, this model reproduces in adult PI rats the main deficits observed in infants with a perinatal history of hypoxia-ischemia and WMD.