Functional Deficit and Recovery of Developing Sensorimotor Networks following Neonatal Hypoxic-Ischemic Injury in the Rat

Neonatal hypoxia-ischemia (HI) is the most important cause of brain injury in the newborn. Here we studied structural alterations and functional perturbations of developing large-scale sensorimotor cortical networks in a rat model of moderate HI at postnatal day 3 (P3). At the morphological level, HI led to a disorganized barrel pattern in the somatosensory cortex without detectable histological changes in the motor cortex. Functional effects were addressed by means of epicranial mapping of somatosensory-evoked potentials (SEPs) during the postischemic recovery period. At P10, SEPs were immature and evoked activity was almost restricted to the somatosensory and motor cortices of the contralateral hemisphere. Peak and topographic analyses of epicranial potentials revealed that responses were profoundly depressed in both sensory and motor areas of HI-lesioned animals. At the end of the postnatal period at P21, responses involved networks in both hemispheres. SEP amplitude was still depressed in the injured sensory region, but it completely recovered in the motor area. These results suggest a process of large-scale network plasticity in sensorimotor circuits after perinatal ischemic injury. The model provides new perspectives for investigating the temporal and spatial characteristics of the recovery process following HI and eventually developing therapeutic intervention

Developmental Changes and Injury Induced Disruption of the Radial Organization of the Cortex in the Immature Rat Brain Revealed by In Vivo Diffusion Tensor MRI

During brain development, morphological changes modify the cortex from its immature radial organization to its mature laminar appearance. Applying in vivo diffusion tensor imaging (DTI), the microstructural organization of the cortex in the immature rat was analyzed and correlated to neurohistopathology. Significant differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were detected between the external (I-III) and deep (IV-VI) cortical layers in postnatal day 3 (P3) and P6 pups. With cortical maturation, ADC was reduced in both cortical regions, whereas a decrease in FA was only seen in the deep layers. A distinct radial organization of the external cortical layers with the eigenvectors perpendicular to the pial surface was observed at both ages. Histology revealed maturational differences in the cortical architecture with increased neurodendritic density and reduction in the radial glia scaffolding. Early DTI after hypoxia-ischemia at P3 shows reduced ADC and FA in the ipsilateral cortex that persisted at P6. Cortical DTI eigenvector maps reveal microstructural disruption of the radial organization corresponding to regions of neuronal death, radial glial disruption, and astrocytosis. Thus, the combined use of in vivo DTI and histopathology can assist in delineating normal developmental changes and postinjury modifications in the immature rodent brai