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NEURAL STEM CELL.
  Term Paper ID:26912
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Summary & critique of article "Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System," by C.B. Johansson, et al.... More...
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Paper Abstract:
Summary & critique of article "Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System," by C.B. Johansson, et al.

Paper Introduction:
IDENTIFICATION OF A NEURAL STEM CELL IN THE ADULT MAMMALIAN CENTRAL NERVOUS SYSTEM: AN ARTICLE SUMMARY & CRITIQUE Introduction The article “Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System” (Johansson, Clarke, & Lendhal, 1999) is summarized and critiqued. Future applications of the findings reported in the article also are addressed. Summary of Article The researchers observed that, while new neurons are added to mammalian central nervous systems and the these new neurons are added in specific regions of the central nervous system, the source of these new neurons has remained somewhat of a mystery. One primary objective of the research, the results of wh

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The alternative experimental methodinvolved injecting a replication-deficient adenovirus expressing lacZ intothe lateral ventricle of adult rats. Theepithelial membrane is integral to the epithelium, which is the tissue thatcovers a surface or lines a tubal passageway or cavity. Reference Johansson, C. Future applications of the findings reported inthe article also are addressed. Based on thisfinding, the researchers concluded ependymal cells are, in fact, neuralstem cells. Thus, it was not a great leap of faith for theresearchers to postulate that neurons added in the ependyma were derivedfrom stem cells. To eliminate the possibility of passive Dil diffusion from thecerebrospinal fluid to subventricular cells over time, the researchersaspirated cerebrospinal fluid from the lateral ventricle from animals thathad received an intra ventricular Dil injection the day before and added itto cultured cells. Further, theresearchers found that injection of the cerebrospinal fluid into thelateral ventricle of another animal did not result in any labeling of cellslining the ventricle. Allsubsequent analyses were done on the hemisphere contralateral to theinjection to exclude the possibility of labeling other cell types along theinjection route. Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System: An Article Summary & Critique Introduction The article "Identification of a Neural Stem Cell in the AdultMammalian Central Nervous System" (Johansson, Clarke, & Lendhal, 1999) issummarized and critiqued. The Dil-labeled cells in theolfactory bulb were immunoreactive for the neuron-specific proteins ?lll-tubulin. To exclude direct cell-to-cell transfer of Dil from the ependymal cells, the researchers co-cultured Dil-labeled ependymal cells with genetically labeled cells fromROSA-26 mice. Theestablishment of a specific identity for the added cells was the secondprimary objective of the research performed. The methods employed by the researchers were thorough and complete.One characteristic of the use of multiple experimental methods was astrengthening of confidence in the reliability and validity of the datagenerated by the researchers, as well as in the findings based on thosedata and the conclusions drawn from those findings. As a consequence, the possibility of Dil transferto the subventricular cells had to be eliminated. The researchers focused on the ependymal cells. L., & Lendhal, U. Identical results were obtained when the same experiments wereperformed in mice. In this method, a singleinjection of the fluorescent label Dil resulted in specific labeling of theependymal layer throughout the ventricular system of adult rats. This research method provided adequate controls toenable the researchers to assure the reliability and validity of the datagenerated by the experimental procedures. The initial restriction of the Dil exclusively to theependymal layer changed over time with an increasing number of Dil-labeledcells appearing in the subventricular zone a few days after the injection.Soon after this outcome, an increasing number of labeled cells was observedin the rostral migratory stream, and within 1 days the first Dil-labeledcells were seen in the olfactory bulb. The method found only weak labeling, indicating to theresearchers that the Dil concentration was very low. Ependymal cells arethose cells situated in the ependyma, which is an epithelial membrane thatlines the ventricles of the brain and the canal of the spinal cord. The researchers then employed an alternative experimental method tospecifically label the ependymal cells as a means of confirming the resultsdiscussed in the preceding paragraph. This method produced no detectable transfer of Dil to theROSA-26 cells. This tissuecontains the ependymal cells. Cell, 96, 25-34. Future Application of Findings One of the potentially more significant of the implications of theresearch reported in the article is the identification of a unique processthrough which neural stem cells respond to injury to the central nervoussystem. The researchers suggested that, proceeding from the identificationof this process, future researchers will be able to identify the molecularmechanisms directing the proliferation and differential of stem cells inresponse to injury. Critique of Article To analyze the involvement of ependymal cells in the hypothesizedprocess, the researchers devised a method to specifically label theependymal layer throughout the neuraxis. The research reported in this article supported the hypothesis thatneurons added to the ependyma are derived from stem cells. According to the researchers, the lower number of lacZ labeled cellsas expected, as the adenovirus is replication deficient and as the labelis, in contrast to Dil, inherited by only a subset of the progeny of theinfected cell. The researchers observedthat, as was the case in the Dil-labeling experiments, lacZ-expressingcells were found in the olfactory bulb 1 days following injection,although in substantially lower numbers. One day after injection, theresearchers found that lacZ expression was exclusively confined toependymal cells and no labeling was evident in the sub ventricular zone.The researchers then sought to identify the molecular basis for thisspecific effect on ependymal cells. To make such an identification, theresearchers studied the distribution of the recently identified adenovirusreceptor, CXADR. In the lateral wall of thelateral ventricle, an increasing number of lacZ-expressing cells wasevident in the sub-ventricular zone over time. According to the researchers, this knowledge, in turn,may lead to the development of effective strategies to either or bothreduce scar formation and stimulate neurogenesis. Prior research findings had suggested that ependymal cells mightderive from stem cells, however, such suggestions had never been validatedby research studies. In was know, however, that stem cells have thecapacity to renew themselves. One primary objective of theresearch, the results of which were reported in this article, thus, was toidentify the source of the neurons added to the central nervous system.The researchers posited that the identification of the source of the addedneurons would, in turn, provide an identity for the cells. (1999 January 8).Identification of a Neural Stem Cell in the Adult Mammalian Central NervousSystem. It also was known that stem cells cangenerate the major classes of central nervous system cell types, whichinclude neurons. This study revealed that, except for scattered cellprocesses in the brain parenchyma, CXADR immunoreactivity was exclusive tothe cell membranes of ependymal cells, and lacZ expression was strong inependymal cells lining the lateral ventricles. B., Clarke, D. The researchers concluded, on the bases of both the Dil andthe adenovirus experiments, that a label uniquely restricted to cells inthe ependymal layer is later found in cells migrating in the rostralmigratory stream and in neurons present in the olfactory bulb. With the attainment ofsuch outcomes in the future, the researchers suggested that the use ofendogenous stem cells to generate new neurons in the treatment of centralnervous system diseases may well be realized. The researchers noted that the results of these experiments criticallydepend on the unique labeling of ependymal cells, but not of cells in thesub-ventricular zone. These data suggested to the researchers that the Dilconcentration in the lateral ventricle drops fast after an intraventricular injection and that a delayed passive labeling of cells in thesub-ventricular zone is highly unlikely. Summary of Article The researchers observed that, while new neurons are added tomammalian central nervous systems and the these new neurons are added inspecific regions of the central nervous system, the source of these newneurons has remained somewhat of a mystery.

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