The adult mammalian subventricular zone (SVZ) contains stem cells that give rise to neurons and glia. In vivo, SVZ progeny migrate 3-8 mm to the olfactory bulb, where they form neurons. We show here that the SVZ of the lateral wall of the lateral ventricles in adult mice is composed of neuroblasts, glial cells, and a novel putative precursor cell. The topographical organization of these cells suggests how neurogenesis and migration are integrated in this region. Type A cells had the ultrastructure of migrating neuronal precursors. These cells were arranged as chains parallel to the walls of the ventricle and were polysialylated neural adhesion cell molecule- (PSA-NCAM), TuJ1- (beta-tubulin), and nestin-positive but GFAP- and vimentin-negative. Chains of Type A cells were ensheathed by two ultrastructurally distinct astrocytes (Type B1 and B2) that were GFAP-, vimentin-, and nestin-positive but PSA-NCAM- and TuJ1-negative. Type A and B2 (but not B1) cells incorporated [3H]thymidine. The most actively dividing cell in the SVZ corresponded to Type C cells, which had immature ultrastructural characteristics and were nestin-positive but negative to the other markers. Type C cells formed focal clusters closely associated with chains of Type A cells. Whereas Type C cells were present throughout the SVZ, they were not found in the rostral migratory stream that links the SVZ with the olfactory bulb. These results suggest that chains of migrating neuroblasts in the SVZ may be derived from Type C cells. Our results provide a topographical model for the adult SVZ and should serve as a basis for the in vivo identification of stem cells in the adult mammalian brain.

https://www.jneurosci.org/content/jneuro/17/13/5046.full.pdf

Cellular Composition and Three-Dimensional Organization of the Subventricular Germinal Zone in the Adult Mammalian Brain

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.27210

Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study Of Liver Diseases and the European Association for the Study of the Liver

A stereotaxic atlas of the rat brain

The developing central nervous system of vertebrates contains an abundant cell type designated radial glial cells. These cells are known as guiding cables for migrating neurons, while their role as precursor cells is less clear. Since radial glial cells express a variety of astroglial characteristics and differentiate as astrocytes after completing their guidance function, they have been considered as part of the glial lineage. Using fluorescence-activated cell sorting, we show here that radial glial cells also are neuronal precursors and only later, after neurogenesis, do they shift towards an exclusive generation of astrocytes. These results thus demonstrate a novel function for radial glial cells, namely their ability to generate two major cell types found in the nervous system, neurons and astrocytes.

/pdf/isolation-of-radial-glial-cells-by-fluorescent-activated-cm91tswy1o.pdf

Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage.

Characterization of CNS precursor subtypes and radial glia.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.21586

Value of the critical flicker frequency in patients with minimal hepatic encephalopathy

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.20565

Oral administration of sildenafil restores learning ability in rats with hyperammonemia and with portacaval shunts

Background and aims Patients with liver cirrhosis may present minimal hepatic encephalopathy (MHE) that can be unveiled using specific neuropsychologic examination. Evaluation of MHE in cirrhotic patients might have prognostic value. The psychometric HE score (PHES) has been recommended as the "gold standard" in the diagnosis of MHE. It has been proposed that critical flicker frequency (CFF) analysis would be useful for easier detection of MHE. It would also be useful to have some peripheral parameter that could reflect the presence of MHE. It has been recently proposed that inflammation-associated alterations and hyperammonemia may cooperate in the induction of hepatic encephalopathy. The aim of the present work was to assess whether there is a correlation between the alterations in parameters reflecting inflammation, hyperammonemia, and the presence of MHE. Methods We have studied in 55 patients with liver cirrhosis and 26 controls the performance in the PHES battery and the CFF, ammonia, and some interleukins (ILs) as inflammatory markers. Results IL-6 and IL-18 were significantly higher (2.5-fold and 2.2-fold, respectively) in patients with MHE than in those without MHE. There were significant correlations between IL-6 or IL-18 levels and PHES score and CFF. Moreover, all patients with MHE had IL-6 levels higher than 11 ng/mL, whereas all patients without MHE had IL-6 levels lower than 11 ng/mL. Conclusions Inflammatory alterations related with IL-6 and IL-18 may contribute to MHE. Serum concentration of IL-6 and IL-18 may be useful to discriminate cirrhotic patients with and without MHE.

IL-6 and IL-18 in blood may discriminate cirrhotic patients with and without minimal hepatic encephalopathy.

In the present study we analyze the events which occur during the early stages of astrogliogenesis by examining the pattern of both GFAP and vimentin gene expression and their corresponding immunoreactive proteins during rat brain development. This study was carried out "in vivo" (whole brain) and "in vitro" (primary culture of radial glia) using immunofluorescence, immunoblotting, and Northern blot analysis. Our results demonstrate that although GFAP immunostaining appeared late in gestation and at day 5 in radial glia cultures, GFAP mRNA expression was first detected, at very low levels, on fetal (F) day 15 and increased to F21. During postnatal development a striking increase in GFAP and its encoding messenger occurs. In contrast, the levels of vimentin and its mRNA expression were very high during the fetal stage (F15 to F21). Thereafter vimentin expression declined during postnatal (P) development until P21 and then remained constant at adult levels. In contrast, an increase in vimentin expression was observed in glial cells throughout the entire culture period. The biological significance of the developmental patterns of GFAP and vimentin expression in astroglial cells. during brain development is discussed.

Developmental pattern of GFAP and vimentin gene expression in rat brain and in radial glial cultures.

Patients with hepatic encephalopathy (HE) may present different neurological alterations including impaired cognitive function and altered motor activity and coordination. HE may lead to coma and death. Many of these neurological alterations are the consequence of altered neurotransmission. Hyperammonemia is a main contributor to the alterations in neurotransmission and in neurological functions in HE. Both glutamatergic and GABAergic neurotransmission are altered in animal models of HE. We review some of these alterations, especially those alterations in glutamatergic neurotransmission responsible for some specific neurological alterations in hyperammonemia and HE: the role 1) of excessive NMDA receptors activation in death induced by acute hyperammonemia; 2) of impaired function of the glutamate-nitric oxide-cGMP pathway, associated to NMDA receptors, in cognitive impairment in chronic HE; 3) of increased extracellular glutamate and activation of metabotropic glutamate receptors in substantia nigra in hypokinesia in chronic HE. The therapeutic implications are discussed. We also review the alterations in the function of the neuronal circuits between basal ganglia-thalamus-cortex modulating motor activity and the role of sequential alterations in glutamatergic and GABAergic neurotransmission in these alterations. HE would be a consequence of altered neuronal communication due to alterations in general neurotransmission involving different neurotransmitter systems in different neurons.

Carmina Montoliu

Papers

Value of the critical flicker frequency in patients with minimal hepatic encephalopathy

Oral administration of sildenafil restores learning ability in rats with hyperammonemia and with portacaval shunts

IL-6 and IL-18 in blood may discriminate cirrhotic patients with and without minimal hepatic encephalopathy.

Developmental pattern of GFAP and vimentin gene expression in rat brain and in radial glial cultures.

Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy