UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Putative Biomarkers of Neuro-restoration in the CNS

Gnanapavan, S; (2013) Putative Biomarkers of Neuro-restoration in the CNS. Doctoral thesis (PhD), UCL (University College London). Green open access

[thumbnail of Gnanapavan Thesis Putative Biomarkers of Neuro-restoration in the CNS_final[1].pdf]
Preview
Text
Gnanapavan Thesis Putative Biomarkers of Neuro-restoration in the CNS_final[1].pdf

Download (2MB) | Preview

Abstract

The aim of this work was to investigate putative biomarkers of neuronal plasticity and repair in the central nervous system. The effects of different disease processes, such as inflammation, demyelination and neurodegeneration were explored. We developed and validated ELISA-based assays for the quantification of neural cell adhesion molecule (NCAM) and growth-associated protein (GAP)-43, two known facilitators of neuronal outgrowth in the nervous system. NCAM isoforms in biological samples were characterised using mass spectrometry. Soluble NCAM was measured in in-vitro and in-vivo models of inflammation/demyelination and neurodegeneration, and across different neurological disorders in the CSF to understand the impact of inflammation and axonal loss on its levels. Recombinant GAP-43 was produced using baculovirus technology and purified in appreciable amounts for use in a new ELISA. Soluble GAP-43 levels were quantified across different neurological disorders in the CSF. Values for CSF NCAM and GAP-43 were correlated with clinical outcome measures. CSF NCAM demonstrated a restricted pattern of expression compared to that of serum whilst GAP-43 is almost exclusively expressed in the CSF, indicating that these biomarkers are intrathecally synthesised. CSF NCAM and GAP-43 levels were lower in neurological disorders with prominent axonal injury; multiple sclerosis, movement disorders, motor neurone disease, Alzheimer’s disease and meningitis. In vitro neuronal cell culture model and in vivo experimental autoimmune encephalomyelitis studies demonstrate that CSF NCAM correlates well with disease progression in multiple sclerosis. A similar relationship was not found with CSF GAP-43. In conclusion, the adult CNS may possess the intrinsic capacity to repair, but this capacity may be dramatically reduced in disease states. Measuring this process may be important in understanding neuronal repair and plasticity.

Type: Thesis (Doctoral)
Qualification: PhD
Title: Putative Biomarkers of Neuro-restoration in the CNS
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/1397881
Downloads since deposit
60Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item