Depicting the anatomy of the gyral white matter: ubi sumus? quo vadimus?

A cerebral gyrus is made up of an external layer of folded cortex and an inner core of white matter. The architecture of the core has specific features that make it distinct from the white matter of the deep brain regions. Limited externally by the grey matter that covers the top of the gyrus and the neighbouring sulci, this gyral white matter is made up of a mix of fibre populations with multiple directions and destinations. The presence of densely packed fibres with multiple crossings, the proximity to the cortex and the existence of inter-regional and inter-individual variations make the task of depicting this microanatomy extremely challenging. The topic is, however, of paramount relevance for both fundamental and applied neurosciences. This fibre colocalization is crucial for the functional role of each cerebral region and is key to clinical manifestations in cases of parenchymal damage. As track tracing, imaging and dissection are based on different biological or physical principles, it is natural for their results to sometimes be different, but they are often complementary. As the amount of available information increases, it becomes fragmented due to the multiplicity of methods, target phenomena and studied species. In this scoping review, we present the key concepts and map the primary sources of evidence regarding identifying the fibre pathways that compose the gyral white matter, enabling the discussion of avenues for future research. The general pattern in which these pathways are distributed in the gyral white matter was detailed, and the main variations as a function of brain topography were explained and illustrated with typical examples.

Histomorphometry of the cortical layers and the dentate nucleus of the human fetal cerebellum.

Objectives: This study was aimed at determining the histomorphometry of the cerebellar cortical laminae and the dentate nucleus of the human fetal cerebellum; the number and shape of the neurons; and the gestational age of appearance of the cerebellar folia, white matter and arbor vitae cerebelli. Methods: Microscopic sections of the human fetal cerebellum stained with hematoxylin and eosin and Bielschowsky silver stain were studied. Results: The thickness of the cortical laminae of the human fetal cerebellum varied among gestational weeks as follows: external granular layer: 36.06 ± 9.36-50.05 ± 34.06 µm, molecular layer: 32.76 ± 17.16-52 ± 28.6 µm, Purkinje cell layer: 9.36 ± 6.8-15.6 ± 4.68 µm and internal granular layer: 66.65 ± 24.42-146.63 ± 47.79 µm. Similarly, the number of neurons per field of view at 1000X under a compound microscope varied among gestational weeks as follows: external granular layer: 89.92 ± 42-142.84 ± 50, molecular layer: 15 ± 12.5-25 ± 8.25, Purkinje cell layer: 3.5 ± 1-5 ± 2.5 and internal granular layer: 98.5 ± 69.75-224 ± 47.White matter in the fetal cerebellum was already present at the age of 12th gestational week, whereas cerebellar folia appeared at 16-20 gestational weeks. Arbor vitae cerebelli and the dentate nucleus became conspicuous after the 20th gestational week. Fetal neurons were round except for Purkinje cells. Conclusions: The thickness and neuronal counts of the human fetal cerebellar cortical layers and the measurements of the dentate nucleus along with other histomorphological features varied with gestational age from the 12th week of gestation until birth.

Comparative role of SOX10 gene in the gliogenesis of central, peripheral, and enteric nervous systems.

SOX10 gene and SOX10 protein are responsible for the gliogenesis of neuroglia from the neural crest cells. Expression of SOX10 gene encodes SOX10 protein which binds with DNA at its minor groove via its HMG domain upon activation. SOX10 protein undergoes bending and changes its conformation after binding with DNA. Via its transactivation domain and HMG domain, it further activates several other transcription factors, these cause gliogenesis of the neural crest cells into neuroglia. In literature, it is stated that the SOX10 gene helps in the formation of schwann cells, oligodendrocytes, and enteric ganglia from neural crest cells. Altered expression of the SOX10 gene results in agliogenesis, dysmyelination, and demyelination in the nervous system as well as intestinal aganglionosis. This review highlighted that there is a role of the SOX10 gene and SOX10 protein in enteric gliogenesis from the neural crest cells.

Histomorphology of enteric neurons and enteric ganglia in different layers of human fetal colon.

Objective: Literature shows very few studies explaining morphology of enteric neurons and ganglia in humans. This study was aimed at determining the morpho-histology of enteric neurons and ganglia in human fetal colon. Methods: Histological sections of human fetal colon were stained with hematoxylin and eosin, Bielschowsky's silver and Masson's trichrome stains to study the morpho-histology of enteric neurons and ganglia. Results: Enteric neurons scattered in the early weeks of development and ganglionated as the fetal age progresses. Migration of enteric neurons was less and in scattered form during early weeks and as the age progresses it was more and in ganglionated form. Enteric neurons were round, oval, pyramidal and flat in all layers of colon. Enteric ganglia in serosa were oval in early weeks, oval and elongated in late weeks whereas in between the muscle layers and submucosa they were few and oval, irregular and elongated. Distance between the enteric ganglia increased in serosa but fluctuated in the remaining layers as the gestational age progressed. Number of enteric neurons and ganglia was more in serosa and less in other layers during early weeks and as the fetal age progressed they decreased in serosa but increased in other layers. Conclusion: There are various shapes and numbers of enteric neurons and ganglia and distances between the ganglia in different layers of fetal colon.

The RET gene encodes RET protein, which triggers intracellular signaling pathways for enteric neurogenesis, and RET mutation results in Hirschsprung's disease.

Enteric neurons and ganglia are derived from vagal and sacral neural crest cells, which undergo migration from the neural tube to the gut wall. In the gut wall, they first undergo rostrocaudal migration followed by migration from the superficial to deep layers. After migration, they proliferate and differentiate into the enteric plexus. Expression of the Rearranged During Transfection (RET) gene and its protein RET plays a crucial role in the formation of enteric neurons. This review describes the molecular mechanism by which the RET gene and the RET protein influence the development of enteric neurons. Vagal neural crest cells give rise to enteric neurons and glia of the foregut and midgut while sacral neural crest cells give rise to neurons of the hindgut. Interaction of RET protein with its ligands (glial cell derived neurotrophic factor (GDNF), neurturin (NRTN), and artemin (ARTN)) and its co-receptors (GDNF receptor alpha proteins (GFRα1-4)) activates the Phosphoinositide-3-kinase-protein kinase B (PI3K-PKB/AKT), RAS mitogen-activated protein kinase (RAS/MAPK) and phospholipase Cγ (PLCγ) signaling pathways, which control the survival, migration, proliferation, differentiation, and maturation of the vagal and sacral neural crest cells into enteric neurons. Abnormalities of the RET gene result in Hirschsprung's disease.

Awareness of cervix cancer risk factors in educated youth: a cross-sectional, questionnaire based survey in India, Nepal, and Sri Lanka.

OBJECTIVE: The main aim of this study was to evaluate the awareness of cervix cancer risk factors among Educated Youth with respect to socio demographic factors. MATERIALS AND METHODS: A cross-sectional questionnaire survey was carried out among 1268 female undergraduate students in Delhi, Mangalore (India), Pokhara (Nepal) and Kandy (Srilanka) between 25 April 2010 and 20 August 2010 using structured questionnaire containing details of awareness of cervix cancer risk factors and socio demographic details. Descriptive statistics and testing of hypothesis were used for the analysis. Data analyzed using EPI INFO and SPSS 16 software. RESULTS: In the 1,268 subjects, the mean age of Indian (528, 41.6%), Nepalese (480, 37.9%) and Srilankan (260, 20.5%) were 18.3 ± SD 0.7, 18.6 ± SD 0.8 and 18.0 ± SD 1.5 years, respectively. Distribution of students according to religion varied across the countries. Majority of the students were Hindus in India (61.4%) and Nepal (89.6%) while in Srilanka the majority (53.8%) were Buddhist. Relationships could be established between nationality and risk factors viz. awareness regarding cervix cancer (p= 0.024), sexual activity at an early age (before 16) can cause cervix cancer (p=0.0001), multiple sex partners can cause cervix cancer (p=0.001), condom/other birth control measures cant prevent HPV infection (p=0.0001), smoking as a risk factor(p=0.0001), hereditary risk factor (p=0.015), and first degree relative (p=0.0001). CONCLUSION: These results indicate that there is an urgent need for a reinvigorated and tailored approach to cervix cancer prevention among the educated youth in India, Nepal and Srilanka. Prevention efforts should be focused on improving social awareness, enforcing education strategies to reduce risk factors and improving the strength and quality of counselling.