Growth of the Human Corpus Callosum: Modular and Laminar Morphogenetic Zones

The purpose of this focused review is to present and discuss recent data on the changing organization of cerebral midline structures that support the growth and development of the largest commissure in humans, the corpus callosum. We will put an emphasis on the callosal growth during the period between 20 and 45 postconceptual weeks (PCW) and focus on the advantages of a correlated histological/magnetic resonance imaging (MRI) approach. The midline structures that mediate development of the corpus callosum in rodents, also mediate its early growth in humans. However, later phases of callosal growth in humans show additional medial transient structures: grooves made up of callosal septa and the subcallosal zone. These modular (septa) and laminar (subcallosal zone) structures enable the growth of axons along the ventral callosal tier after 18 PCW, during the rapid increase in size of the callosal midsagittal cross-section area. Glial fibrillary acidic protein positive cells, neurons, guidance molecule semaphorin3A in cells and extracellular matrix (ECM), and chondroitin sulfate proteoglycan in the ECM have been identified along the ventral callosal tier in the protruding septa and subcallosal zone. Postmortem MRI at 3 T can demonstrate transient structures based on higher water content in ECM, and give us the possibility to follow the growth of the corpus callosum in vivo, due to the characteristic MR signal. Knowledge about structural properties of midline morphogenetic structures may facilitate analysis of the development of interhemispheric connections in the normal and abnormal fetal human brain

Changes of the Corpus Callosum in Children who Suffered Perinatal Injury of the Periventricular Crossroads of Pathways

There is a high incidence of periventricular leukomalacia, caused by hypoxia-ischemia, in preterm infants. These lesions damage the periventricular crossroads of commissural, projection and associative pathways, which are in a close topographical relationship with the lateral ventricles. We explored to what extent abnormalities of echogenicity of the periventricular crossroads correlate with changes in size of the corpus callosum. Our study included nine infants (gestation from 26–41 weeks; birth weight between 938–4450 grams) with perinatal brain injury. Periventricular areas, which topographically correspond to the frontal, main and occipital crossroad, were readily visualized by cranial ultrasound scans, performed during the first two weeks after birth. Corpus callosum mediosagittal area measurements were performed using magnetic resonance images, acquired between the first and sixth postnatal month (postmenstrual age 40–49 weeks). We found a statistically significant correlation between the increased echogenicity in the crossroad areas and the decrease of the corpus callosum midsagittal area (p<0.05). This supports the hypothesis that callosal fibers can be damaged, during growth through the periventricular crossroads of pathways

Developmental changes in the midsagittal are of the corpus callosum as indicators of perinatal growth of interhemispheric connections in humans

Korpus kalozum je najveći komisuralni put bijele tvari velikog mozga, koji spaja glavninu neokortikalnih područja te je najrazvijeniji kod čovjeka. Njegova važnost u kliničkoj praksi leži u činjenici da se razdoblje njegovog intenzivnog razvitka poklapa s nastupom hipoksično-ishemijskih lezija prerano rođene djece. Kod čovjeka mediosagitalna površina korpusa kalozuma prolazi specifičnu promjenu, koja se očituje stankom u njegovom rastu. Pokazali smo da glijalni elementi korpusa kalozuma ne predstavljaju značajan strukturni čimbenik koji bi doprinosio navedenoj promjeni površine. Smatramo da je promjena površine rezultat promjene broja i gustoće aksonalnih elemenata. U razdoblju od 28. do 35. gestacijskog tjedna vjerojatni je uzrok promjene površine pomak fronte rasta kalozalnih aksona preko medijalne linije. U razdoblju nakon 35. gestacijskog tjedna promjena površine je vjerojatno posljedica kombinacije smanjenja broja aksonalnih elemenata uz povećanje promjera aksona, a nakon rođena i mijelinizacije. Na uzorcima korpusa kalozuma štakora smo pokazali da je odnos ukupnog broja aksona u korpusu kalozumu i njegove površine ovisna o dobi u razdoblju od nultog do dvanaestog postnatalnog dana. Visoki udio čunjića rasta upućuje da se u ovom razdoblju još uvijek odvija visoki stupanj urastanja aksona. Smatramo da rezultati ove studije predstavljaju snažan temelj daljnjim istraživanjima normalnog razvitka i patologije korpusa kalozuma.Corpus callosum is the biggest commissural pathway of the telencephalon, connecting the majority of neocortical areas, hence it is most complex in the human. Its importance in clinical research lies in the fact that the period of its most prominent development coincides with the occurence of hypoxic-ischemic lesions in preterm-born infants. The midsagittal area of the corpus callosum in humans goes through a specific change, which is manifested by a pause in its growth. We have shown that the glial elements do not represent a significant structural factor, which would contribute to the change in area of the corpus callosum. We are convinced that the area change is a result of the change in number and density of axonal elements. In the period between 28 and 35 gestational weeks, the most likely cause is the translocation of the growth front from the midline. After 35 gestational weeks the described change in area is most likely a result of a combination of axonal element number decrease and axonal diametar increase, and additionally myelination after birth. On rat callosal samples we showed that the relationship between axonal number and axonal midsagittal area is age-dependant, in the period from postnatal day zero to twelve. High proportion of growth cones in this period indicates that there is still a substantial ingrowth of axons. The results of this study represent a strong foundation for future research of normal development and pathological changes of the corpus callosum

Developmental changes in the midsagittal are of the corpus callosum as indicators of perinatal growth of interhemispheric connections in humans

Korpus kalozum je najveći komisuralni put bijele tvari velikog mozga, koji spaja glavninu neokortikalnih područja te je najrazvijeniji kod čovjeka. Njegova važnost u kliničkoj praksi leži u činjenici da se razdoblje njegovog intenzivnog razvitka poklapa s nastupom hipoksično-ishemijskih lezija prerano rođene djece. Kod čovjeka mediosagitalna površina korpusa kalozuma prolazi specifičnu promjenu, koja se očituje stankom u njegovom rastu. Pokazali smo da glijalni elementi korpusa kalozuma ne predstavljaju značajan strukturni čimbenik koji bi doprinosio navedenoj promjeni površine. Smatramo da je promjena površine rezultat promjene broja i gustoće aksonalnih elemenata. U razdoblju od 28. do 35. gestacijskog tjedna vjerojatni je uzrok promjene površine pomak fronte rasta kalozalnih aksona preko medijalne linije. U razdoblju nakon 35. gestacijskog tjedna promjena površine je vjerojatno posljedica kombinacije smanjenja broja aksonalnih elemenata uz povećanje promjera aksona, a nakon rođena i mijelinizacije. Na uzorcima korpusa kalozuma štakora smo pokazali da je odnos ukupnog broja aksona u korpusu kalozumu i njegove površine ovisna o dobi u razdoblju od nultog do dvanaestog postnatalnog dana. Visoki udio čunjića rasta upućuje da se u ovom razdoblju još uvijek odvija visoki stupanj urastanja aksona. Smatramo da rezultati ove studije predstavljaju snažan temelj daljnjim istraživanjima normalnog razvitka i patologije korpusa kalozuma.Corpus callosum is the biggest commissural pathway of the telencephalon, connecting the majority of neocortical areas, hence it is most complex in the human. Its importance in clinical research lies in the fact that the period of its most prominent development coincides with the occurence of hypoxic-ischemic lesions in preterm-born infants. The midsagittal area of the corpus callosum in humans goes through a specific change, which is manifested by a pause in its growth. We have shown that the glial elements do not represent a significant structural factor, which would contribute to the change in area of the corpus callosum. We are convinced that the area change is a result of the change in number and density of axonal elements. In the period between 28 and 35 gestational weeks, the most likely cause is the translocation of the growth front from the midline. After 35 gestational weeks the described change in area is most likely a result of a combination of axonal element number decrease and axonal diametar increase, and additionally myelination after birth. On rat callosal samples we showed that the relationship between axonal number and axonal midsagittal area is age-dependant, in the period from postnatal day zero to twelve. High proportion of growth cones in this period indicates that there is still a substantial ingrowth of axons. The results of this study represent a strong foundation for future research of normal development and pathological changes of the corpus callosum

Razvojne promjene mediosagitalnog presjeka korpusa kalozuma kao pokazatelji perinatalnog rasta interhemisferičnih veza u mozgu čovjeka [Developmental changes in the midsagittal are of the corpus callosum as indicators of perinatal growth of interhemispheric connections in humans]

Corpus callosum is the biggest commissural pathway of the telencephalon, connecting the majority of neocortical areas, hence it is most complex in the human. Its importance in clinical research lies in the fact that the period of its most prominent development coincides with the occurence of hypoxic-ischemic lesions in preterm-born infants. The midsagittal area of the corpus callosum in humans goes through a specific change, which is manifested by a pause in its growth. We have shown that the glial elements do not represent a significant structural factor, which would contribute to the change in area of the corpus callosum. We are convinced that the area change is a result of the change in number and density of axonal elements. In the period between 28 and 35 gestational weeks, the most likely cause is the translocation of the growth front from the midline. After 35 gestational weeks the described change in area is most likely a result of a combination of axonal element number decrease and axonal diametar increase, and additionally myelination after birth. On rat callosal samples we showed that the relationship between axonal number and axonal midsagittal area is age-dependant, in the period from postnatal day zero to twelve. High proportion of growth cones in this period indicates that there is still a substantial ingrowth of axons. The results of this study represent a strong foundation for future research of normal development and pathological changes of the corpus callosum

Developmental changes in the midsagittal are of the corpus callosum as indicators of perinatal growth of interhemispheric connections in humans

Korpus kalozum je najveći komisuralni put bijele tvari velikog mozga, koji spaja glavninu neokortikalnih područja te je najrazvijeniji kod čovjeka. Njegova važnost u kliničkoj praksi leži u činjenici da se razdoblje njegovog intenzivnog razvitka poklapa s nastupom hipoksično-ishemijskih lezija prerano rođene djece. Kod čovjeka mediosagitalna površina korpusa kalozuma prolazi specifičnu promjenu, koja se očituje stankom u njegovom rastu. Pokazali smo da glijalni elementi korpusa kalozuma ne predstavljaju značajan strukturni čimbenik koji bi doprinosio navedenoj promjeni površine. Smatramo da je promjena površine rezultat promjene broja i gustoće aksonalnih elemenata. U razdoblju od 28. do 35. gestacijskog tjedna vjerojatni je uzrok promjene površine pomak fronte rasta kalozalnih aksona preko medijalne linije. U razdoblju nakon 35. gestacijskog tjedna promjena površine je vjerojatno posljedica kombinacije smanjenja broja aksonalnih elemenata uz povećanje promjera aksona, a nakon rođena i mijelinizacije. Na uzorcima korpusa kalozuma štakora smo pokazali da je odnos ukupnog broja aksona u korpusu kalozumu i njegove površine ovisna o dobi u razdoblju od nultog do dvanaestog postnatalnog dana. Visoki udio čunjića rasta upućuje da se u ovom razdoblju još uvijek odvija visoki stupanj urastanja aksona. Smatramo da rezultati ove studije predstavljaju snažan temelj daljnjim istraživanjima normalnog razvitka i patologije korpusa kalozuma.Corpus callosum is the biggest commissural pathway of the telencephalon, connecting the majority of neocortical areas, hence it is most complex in the human. Its importance in clinical research lies in the fact that the period of its most prominent development coincides with the occurence of hypoxic-ischemic lesions in preterm-born infants. The midsagittal area of the corpus callosum in humans goes through a specific change, which is manifested by a pause in its growth. We have shown that the glial elements do not represent a significant structural factor, which would contribute to the change in area of the corpus callosum. We are convinced that the area change is a result of the change in number and density of axonal elements. In the period between 28 and 35 gestational weeks, the most likely cause is the translocation of the growth front from the midline. After 35 gestational weeks the described change in area is most likely a result of a combination of axonal element number decrease and axonal diametar increase, and additionally myelination after birth. On rat callosal samples we showed that the relationship between axonal number and axonal midsagittal area is age-dependant, in the period from postnatal day zero to twelve. High proportion of growth cones in this period indicates that there is still a substantial ingrowth of axons. The results of this study represent a strong foundation for future research of normal development and pathological changes of the corpus callosum

Perinatal and early postnatal reorganization of the subplate and related cellular compartments in the human cerebral wall as revealed by histological and MRI approaches

We analyzed the developmental history of the subplate and related cellular compartments of the prenatal and early postnatal human cerebrum by combining postmortem histological analysis with in vivo MRI. Histological analysis was performed on 21 postmortem brains (age range: 26 postconceptional weeks to 6.5 years) using Nissl staining, AChE-histochemistry, PAS-Alcian blue histochemistry, Gallyas' silver impregnation, and immunocytochemistry for MAP2, synaptophysin, neurofilament, chondroitin sulfate, fibronectin, and myelin basic protein. The histological findings were correlated with in vivo MRI findings obtained in 30 age-matched fetuses, infants, and children. We analyzed developmental reorganization of major cellular (cell bodies, growing axons) and extracellular (extracellular matrix) components of the subplate and the developing cortex/white matter interface. We found that perinatal and postnatal reorganization of these tissue components is protracted (extending into the second year of life) and characterized by well-delineated, transient and previously undescribed structural and molecular changes at the cortex/white matter interface. The findings of this study are clinically relevant because they may inform and guide a proper interpretation of highly dynamic and hitherto puzzling changes of cortical thickness and cortical/white matter interface as described in current in vivo MRI studies