The objective of this paper was to collect normative data essential for analyzing the subplate (SP) role in pathogenesis of developmental disorders, characterized by abnormal circuitry, such as hypoxic-ischemic lesions, autism and schizophrenia. The main cytological features of the SP, such as low cell density, early differentiation of neurons and glia, plexiform arrangement of axons and dendrites, presence of synapses and a large amount of extracellular matrix (ECM) distinguish this compartment from the cell-dense cortical plate (CP; towards pia) and large fiber bundles of external axonal strata of fetal white matter (towards ventricle). For SP delineation from these adjacent layers based on combined cytological criteria, we analyzed the sublaminar distribution of different microstructural elements and the associated maturational gradients throughout development, using immunocytochemical and histological techniques on postmortem brain material (Zagreb Neuroembryological Collection). The analysis revealed that the SP compartment of the lateral neocortex shows changes in laminar organization throughout fetal development: the monolayer in the early fetal period (presubplate) undergoes dramatic bilaminar transformation between 13 and 15 postconceptional weeks (PCW), followed by subtle sublamination in three 'floors' (deep, intermediate, superficial) of midgestation (15-21 PCW). During the stationary phase (22-28 PCW), SP persists as a trilaminar compartment, gradually losing its sublaminar organization towards the end of gestation and remains as a single layer of SP remnant in the newborn brain. Based on these sublaminar transformations, we have documented developmental changes in the distribution, maturational gradients and expression of molecular markers in SP synapses, transitional forms of astroglia, neurons and ECM, which occur concomitantly with the ingrowth of thalamo-cortical, basal forebrain and corticocortical axons in a deep to superficial fashion. The deep SP is the zone of ingrowing axons -'entrance (ingrowth) zone'. The process of axonal ingrowth begins with thalamo-cortical fibers and basal forebrain afferents, indicating an oblique geometry. During the later fetal period, deep SP receives long cortico-cortical axons exhibiting a tangential geometry. Intermediate SP ('proper') is the navigation and 'nexus' sublamina consisting of a plexiform arrangement of cellular elements providing guidance and substrate for axonal growth, and also containing transient connectivity of dendrites and axons in a tangential plane without radial boundaries immersed in an ECM-rich continuum. Superficial SP is the axonal accumulation ('waiting compartment') and target selection zone, indicating a dense distribution of synaptic markers, accumulation of thalamo-cortical axons (around 20 PCW), overlapping with dendrites from layer VI neurons. In the late preterm brain period, superficial SP contains a chondroitin sulfate non-immunoreactive band. The developmental dynamics for the distribution of neuronal, glial and ECM marker...

Development of the cerebral wall is characterized by partially overlapping histogenetic events. However, little is known with regards to when, where, and how growing axonal pathways interact with progenitor cell lineages in the proliferative zones of the human fetal cerebrum. We analyzed the developmental continuity and spatial distribution of the axonal sagittal strata (SS) and their relationship with proliferative zones in a series of human brains (8–40 post-conceptional weeks; PCW) by comparing histological, histochemical, and immunocytochemical data with magnetic resonance imaging (MRI). Between 8.5 and 11 PCW, thalamocortical fibers from the intermediate zone (IZ) were initially dispersed throughout the subventricular zone (SVZ), while sizeable axonal “invasion” occurred between 12.5 and 15 PCW followed by callosal fibers which “delaminated” the ventricular zone-inner SVZ from the outer SVZ (OSVZ). During midgestation, the SS extensively invaded the OSVZ, separating cell bands, and a new multilaminar axonal-cellular compartment (MACC) was formed. Preterm period reveals increased complexity of the MACC in terms of glial architecture and the thinning of proliferative bands. The addition of associative fibers and the formation of the centrum semiovale separated the SS from the subplate. In vivo MRI of the occipital SS indicates a “triplet” structure of alternating hypointense and hyperintense bands. Our results highlighted the developmental continuity of sagittally oriented “corridors” of projection, commissural and associative fibers, and histogenetic interaction with progenitors, neurons, and glia. Histogenetical changes in the MACC, and consequently, delineation of the SS on MRI, may serve as a relevant indicator of white matter microstructural integrity in the developing brain.

Preterm birth is associated with a wide range of adverse developmental outcomes, including sensory, motor, cognitive and language impairments, and behavioral or attention problems. Subtle motor deficits that might emerge in premature infants with no evident or with mild brain injury encompass qualitative and quantitative aspects of motor behavior. This prospective cohort study provided an evaluation of the relationship between brain tissue volumes revealed by magnetic resonance imaging (MRI) at term‐equivalent age and motor behavior in infancy in very preterm infants (total number = 40; mean gestational age = 28 weeks + 4 days; mean birth weight = 1190 g) without evident or with mild brain injury. Infants were recruited at birth and assessed at 12 months corrected age using the tool for qualitative and quantitative assessment of motor behavior, infant motor profile. The brain tissue was segmented first using advanced segmentation techniques and the volumes were measured by summing the volumes of all voxels belonging to a particular tissue class. The associations between volumetric brain MRI measures with motor behavior were explored using linear regression analyses. Results showed that larger total brain volumes were associated with higher motor score. Similar relationships were documented for parietal lobe, deep gray matter, and cerebellum volumes. Volumetric quantitative data of brain structures may serve as biomarkers for subtle motor deficits described in very preterm born infants without or with mild brain lesions apparent on MRI.

No abstract

No abstract