Regulation of Oligodendrogenesis in a Rat Contusive Spinal Cord Injury
type: CreativeWork
description: "Loss of oligodendrocytes (OLs) and ensuing demyelination significantly hamper functional recovery following traumatic spinal cord injury (SCI). Although proliferating glial progenitor cells (GPCs) are present in the lesioned spinal cord, spontaneous remyelination is extremely limited. The failure of remyelination after SCI may be due to inadequate signaling to generate sufficient OLs from GPCs. In this thesis research, I tested a hypothesis that manipulation of post-injury microenvironment or intrinsic transcriptional machinery could enhance the extent of oligodendrogenesis in the lesioned spinal cord. Specifically, ex vivo delivery of vascular endothelial growth factor (VEGF) was employed to increase oligodendrogenesis in rat spinal cord contusion model. I also delivered Olig genes to the proliferating GPCs to examine if activation of transcription factors which are required for proper development oligodendrocytes can promote oligodendrogenesis in injured adult spinal cord. VEGF exerts various trophic effects for neural cells including neural stem and/or progenitors in addition to stimulating angiogenesis. The first part of my thesis study delivered VEGF gene carried by immortalized human neural stem cells one week after contusion injury and examined whether the ex vivo VEGF delivery promoted the proliferation and differentiation of GPCs. The ex vivo approach resulted in a marked elevation of VEGF in the injured spinal cord tissue and a concomitant increase in phosphorylation of VEGF receptor flk-1. Stereological counting of BrdU+ cells revealed that the ex vivo VEGF delivery significantly enhanced cellular proliferation at 2 weeks after SCI. The number of proliferating NG2+ glial progenitor cells (NG2+/BrdU+) was also increased. Furthermore, the VEGF delivery increased the number of early proliferating cells that differentiated into mature oligodendrocytes, but not astrocytes, at 6 weeks after SCI. F3.VEGF treatment also increased the density of blood vessels in …
abstract: "Loss of oligodendrocytes (OLs) and ensuing demyelination significantly hamper functional recovery following traumatic spinal cord injury (SCI). Although proliferating glial progenitor cells (GPCs) are present in the lesioned spinal cord, spontaneous remyelination is extremely limited. The failure of remyelination after SCI may be due to inadequate signaling to generate sufficient OLs from GPCs. In this thesis research, I tested a hypothesis that manipulation of post-injury microenvironment or intrinsic transcriptional machinery could enhance the extent of oligodendrogenesis in the lesioned spinal cord. Specifically, ex vivo delivery of vascular endothelial growth factor (VEGF) was employed to increase oligodendrogenesis in rat spinal cord contusion model. I also delivered Olig genes to the proliferating GPCs to examine if activation of transcription factors which are required for proper development oligodendrocytes can promote oligodendrogenesis in injured adult spinal cord. VEGF exerts various trophic effects for neural cells including neural stem and/or progenitors in addition to stimulating angiogenesis. The first part of my thesis study delivered VEGF gene carried by immortalized human neural stem cells one week after contusion injury and examined whether the ex vivo VEGF delivery promoted the proliferation and differentiation of GPCs. The ex vivo approach resulted in a marked elevation of VEGF in the injured spinal cord tissue and a concomitant increase in phosphorylation of VEGF receptor flk-1. Stereological counting of BrdU+ cells revealed that the ex vivo VEGF delivery significantly enhanced cellular proliferation at 2 weeks after SCI. The number of proliferating NG2+ glial progenitor cells (NG2+/BrdU+) was also increased. Furthermore, the VEGF delivery increased the number of early proliferating cells that differentiated into mature oligodendrocytes, but not astrocytes, at 6 weeks after SCI. F3.VEGF treatment also increased the density of blood vessels in …
author: 김, 혁민
language: en
keywords: Spinal Cord Injury, Remyelination, Glial Progeniter Cells, Oligodendrogenesis, NG2, APC-CC1
date published: 2011-01-26T07:35:26Z
date modified: 2026-07-24T00:51:19Z
provider: Ajou University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Ajou University