Neurogenesis from Neural Stem Cells, Ependymal Cells and Fibroblasts
type: CreativeWork
description: Stroke is a major cause of death and disability around the world. Stroke leads to loss of neurons and also other cells in the brain due to lack of blood supply. Currently no therapies are available to treat stroke-related disability. It has been shown that stroke leads to increased neurogenesis, birth of new neurons, within the brain. This increased neurogenesis is not sufficient to restore lost function. There is a need to develop therapies for neuronal replacement by improving neurogenesis within the brain and / or transplanting neurons. Cortical strokes lead to more disability after stroke as compared to those affecting the striatum, and whether cortical neurogenesis occurs after stroke is controversial. Cell transplantation may be the key to cortical repair after stroke. Reports have identified positive but very few negative regulators of neurogenesis after stroke, and suggested that ependymal cells can also contribute to stroke-induced neurogenesis. Transplantation of neurons generated from different sources such as fetal brain, embryonic stem cells and induced pluripotent stem cells are associated with ethical issues and carry the risk of immune rejection and tumorigenicity. Direct conversion of patient’s own skin cells to neurons could overcome these problems and potentially restore function after transplantation in stroke-damaged brain. In this thesis we have used transgenic models, viral vectors, electroporation-mediated gene delivery and overexpression of transcription factors to demonstrate neurogenesis from neural stem cells, ependymal cells in the lateral ventricular wall and fibroblasts. We show that Lnk, a known inhibitor of hematopoietic stem cell self-renewal, is also expressed in the brain. Overexpression or removal of Lnk expression leads to decreased or increased neurogenesis in vitro respectively. When brain is damaged by stroke there is increased proliferation of neural stem cells in animals without Lnk expression. This was not observed in stat…
abstract: Stroke is a major cause of death and disability around the world. Stroke leads to loss of neurons and also other cells in the brain due to lack of blood supply. Currently no therapies are available to treat stroke-related disability. It has been shown that stroke leads to increased neurogenesis, birth of new neurons, within the brain. This increased neurogenesis is not sufficient to restore lost function. There is a need to develop therapies for neuronal replacement by improving neurogenesis within the brain and / or transplanting neurons. Cortical strokes lead to more disability after stroke as compared to those affecting the striatum, and whether cortical neurogenesis occurs after stroke is controversial. Cell transplantation may be the key to cortical repair after stroke. Reports have identified positive but very few negative regulators of neurogenesis after stroke, and suggested that ependymal cells can also contribute to stroke-induced neurogenesis. Transplantation of neurons generated from different sources such as fetal brain, embryonic stem cells and induced pluripotent stem cells are associated with ethical issues and carry the risk of immune rejection and tumorigenicity. Direct conversion of patient’s own skin cells to neurons could overcome these problems and potentially restore function after transplantation in stroke-damaged brain. In this thesis we have used transgenic models, viral vectors, electroporation-mediated gene delivery and overexpression of transcription factors to demonstrate neurogenesis from neural stem cells, ependymal cells in the lateral ventricular wall and fibroblasts. We show that Lnk, a known inhibitor of hematopoietic stem cell self-renewal, is also expressed in the brain. Overexpression or removal of Lnk expression leads to decreased or increased neurogenesis in vitro respectively. When brain is damaged by stroke there is increased proliferation of neural stem cells in animals without Lnk expression. This was not observed in stat…
author: Devaraju, Karthikeyan
language: eng
keywords: Neurology, adult neurogenesis, stroke, neural stem cells, Lnk, ependymal cells, FoxJ1, cortical reprogramming
date published: 2014
date modified: 2026-07-24T02:59:49Z
provider: University of Lund
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Neurology, Lund