Slit2, a branching-arborization factor for sensory axons in the Mammalian CNS. (65/601)

Axons that carry information from the sensory periphery first elongate unbranched and form precisely ordered tracts within the CNS. Later, they begin collateralizing into their proper targets and form terminal arbors. Target-derived factors that govern sensory axon elongation and branching-arborization are not well understood. Here we report that Slit2 is a major player in branching-arborization of central trigeminal axons in the brainstem. Embryonic trigeminal axons initially develop unbranched as they form the trigeminal tract within the lateral brainstem; later, they emit collateral branches into the brainstem trigeminal nuclei and form terminal arbors therein. In whole-mount explant cultures of this pathway, embryonic day 15 (E15) rat central trigeminal axons retain their unbranched growth within the tract, whereas E17 trigeminal axons show branching and arborization in the brainstem trigeminal nuclei, much like that seen in vivo. Similar observations were made in E13 and E15 mouse embryos. We cocultured Slit2-expressing tissues or cells with the whole-mount explant cultures of the central trigeminal pathway derived from embryonic rats or mice. When central trigeminal axons are exposed to ectopic Slit2 during their elongation phase, they show robust and premature branching and arborization. Blocking available Slit2 reverses this effect on axon growth. Spatiotemporal expression of Slit2 and Robo receptor mRNAs within the brainstem trigeminal nuclei and the trigeminal ganglion during elongation and branching-arborization further corroborates our experimental results.  (+info)

Basement membrane type IV collagen molecules in the choroid plexus, pia mater and capillaries in the mouse brain. (66/601)

We investigated the differential distribution of basement membrane type IV collagen a chains in the mouse brain by immunohistochemistry using a chain-specific monoclonal antibodies. Subendothelial basement membranes were found to contain alpha1 and alpha2 chains. Basement membranes surrounding smooth muscle cells on blood vascular walls were immunoreactive for alpha1 and alpha2 chains but not for alpha5 and alpha6 chains. Interestingly, the pia mater contained a thin basement membrane which was positive for alpha1, alpha2, alpha5, and alpha6 chains, suggesting that glia limitans superficialis coheres basement membranes containing [alpha1(IV)]2alpha2(IV) and [alpha5(IV)]2alpha6(IV) molecules. In contrast, capillaries always possessed thin basement membranes of [alpha1(IV)]2alpha2(IV) molecules. Cerebrospinal fluid is produced through filtration of blood at the choroid plexus, where two distinct basement membranes were detected by anti-al and anti-alpha2 antibodies. The subendothelial basement membrane appeared to consist of [alpha1(IV)]2alpha2(IV) molecules, whereas the subependymal basement membrane in the choroid plexus was strongly positive for alpha3, alpha4, and alpha5 chains, indicating that the filtering unit was composed of alpha3(IV)alpha4(IV)alpha5(IV) molecules. That the specific localizations of these molecules are shared by renal glomeruli and the choroid plexus leads us to hypothesize that the supramolecular network containing alpha3(IV) alpha4(IV)alpha5(IV) molecules may function as a permeability selective barrier.  (+info)

Early development and rupture of de novo aneurysm--case report. (67/601)

A 38-year-old non-smoker man presented with a ruptured aneurysm one month after clipping of a previous aneurysm. He was first admitted because of sudden onset of severe headache. Brain computed tomography showed subarachnoid hemorrhage. Angiography showed an aneurysm of the left anterior choroidal artery which was surgically clipped. Two weeks later, he was discharged without neurological deficits. One month after the initial hemorrhage, he was readmitted to the emergency room with stuporous mentality. Repeat angiography showed two aneurysms of the A2 portion of the left anterior cerebral artery which were not demonstrated by the initial angiography. The diagnosis was de novo aneurysms. The larger aneurysm was clipped and the other was coated. De novo aneurysm should be suspected if a patient with a previously clipped aneurysm complains of typical headache or any suggestive symptoms or signs of cranial nerve dysfunction, especially if known risk factors are present.  (+info)

BMP signaling is required locally to pattern the dorsal telencephalic midline. (68/601)

BMPs have been proposed to pattern the medial-lateral axis of the telencephalon in a concentration-dependent manner, thus helping to subdivide the embryonic telencephalon into distinct forebrain regions. Using a CRE/loxP genetic approach, we tested this hypothesis by disrupting the Bmpr1a gene in the telencephalon. In mutants, BMP signaling was compromised throughout the dorsal telencephalon, but only the most dorsalmedial derivative, the choroid plexus, failed to be specified or differentiate. Choroid plexus precursors remained proliferative and did not adopt the fate of their lateral telencephalic neighbors. These results demonstrate that BMP signaling is required for the formation of the most dorsal telencephalic derivative, the choroid plexus, and that BMP signaling plays an essential role in locally patterning the dorsal midline. Our data fail to support a more global, concentration-dependent role in specifying telencephalic cell fates.  (+info)

Mechanism of the reduced elimination clearance of benzylpenicillin from cerebrospinal fluid in rats with intracisternal administration of lipopolysaccharide. (69/601)

The mechanism responsible for the reduced clearance of benzylpenicillin (BPC) from the cerebrospinal fluid (CSF) was investigated in rats that received an intracisternal administration of lipopolysaccharide (LPS). BPC was intraventricularly injected and its elimination from the CSF studied. During the inflammation created by the LPS administration to the cisterna magna, the clearance of BPC and taurine from the CSF was significantly reduced but reverted to the control level when N-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, was intracisternally administered. The in vitro uptake of BPC and taurine was significantly reduced in the choroid plexus (CP, the blood-CSF barrier) of rats with experimental inflammation and in control CP that had been pretreated with sodium nitroprusside (SNP, an NO donor). Interestingly, the clearance and CP uptake of formycin B, a substrate for a nucleoside transporter, were not affected by the experimental inflammation or by pretreatement with SNP. These observations suggest that the BPC transporter, and probably other transport systems as well, is functionally sensitive to NO in the blood-CSF barrier. Therefore, functional impairment of BPC transport in the CP by NO may be partly responsible for the increase in BPC concentration in the CSF during inflammation such as that caused by meningitis.  (+info)

Changes in the surface features of choroid plexus of the rat following the administration of acetazolamide and other drugs which affect CSF secretion. (70/601)

The surface of the choroid plexus of the rat was examined by scanning electron microscopy before and after administration of acetazolamide and other drugs (cardiac glycosides and pilocarpine) which affect the rate of secretion of the CSF. In control animals, bleb-covered cells were more common on the IVth ventricle choroid plexus than on the lateral ventricle choroid plexus (20 per specimen compared to 0-3 per specimen). Following administration of acetazolamide the number of bleb-covered cells was reduced significantly (P less than 0-001). The effects of the other drugs were less well defined. Since acetazolamide is known to interfere with the active transport of the extra chloride ions normally added to the CSF in the IVth ventricle, it is suggested that the bleb-covered cells of the IVth ventricle choroid plexus are the specific site for chloride secretion.  (+info)

Implication of caspases during maedi-visna virus-induced apoptosis. (71/601)

Maedi-visna virus (MVV) causes encephalitis, pneumonia and arthritis in sheep. In vitro, MVV infection and replication lead to strong cytopathic effects characterized by syncytia formation and subsequent cellular lysis. It was demonstrated previously that MVV infection in vitro induces cell death of sheep choroid plexus cells (SCPC) by a mechanism that can be associated with apoptotic cell death. Here, the relative implication of several caspases during acute infection with MVV is investigated by employing diverse in vitro and in situ strategies. It was demonstrated using specific pairs of caspase substrates and inhibitors that, during in vitro infection of SCPC by MVV, the two major pathways of caspase activation (i.e. intrinsic and extrinsic pathways) were stimulated: significant caspase-9 and -8 activities, as well as caspase-3 activity, were detected. To study the role of caspases during MVV infection in vitro, specific, cell-permeable, caspase inhibitors were used. First, these results showed that both z-DEVD-FMK (a potent inhibitor of caspase-3-like activities) and z-VAD-FMK (a broad spectrum caspase inhibitor) inhibit caspase-9, -8 and -3 activities. Second, both irreversible caspase inhibitors, z-DEVD-FMK and z-VAD-FMK, delayed MVV-induced cellular lysis as well as virus growth. Third, during SCPC in vitro infection by MVV, cells were positively stained with FITC-VAD-FMK, a probe that specifically stains cells containing active caspases. In conclusion, these data suggest that MVV infection in vitro induces SCPC cell death by a mechanism that is strongly dependent on active caspases.  (+info)

Establishment and characterization of an immortalized Z310 choroidal epithelial cell line from murine choroid plexus. (72/601)

The choroid plexus plays a wide range of roles in brain development, maturation, aging process, endocrine regulation, and pathogenesis of certain neurodegenerative diseases. To facilitate in vitro study, we have used a gene transfection technique to immortalize murine choroidal epithelial cells. A viral plasmid (pSV3neo) was inserted into the host genome of primary choroidal epithelia by calcium phosphate precipitation. The transfected epithelial cells, i.e., Z310 cells, that survived from cytotoxic selection expressed SV40 large-T antigen throughout the life span, suggesting a successful gene transfection. The cells displayed the same polygonal epithelial morphology as the starting cells by light microscopy. Immunocytochemical studies demonstrate the presence of transthyretin (TTR), a thyroxine transport protein known to be exclusively produced by the choroidal epithelia in the CNS, in both transfected and starting cells. Western blot analyses further confirm the production and secretion of TTR by these cells. The mRNAs encoding transferrin receptor (TfR) were identified by Northern blot analyses. The cells grow at a steady rate, currently in the 110th passage with a population doubling time of 20-22 h in the established culture. When Z310 cells were cultured onto a Trans-well apparatus, the cells formed an epithelial monolayer similar to primary choroidal cells, possessing features such as an uneven fluid level between inner and outer chambers and an electrical resistance approximately 150-200 omega-cm(2). These results indicate that immortalized Z310 cells possess the characteristics of choroidal epithelia and may have the potential for application in blood-CSF barrier (BCB) research.  (+info)