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Characterizing the expression profile of angiogenic proteins after acute spinal cord injury

University of British Columbia

Spinal cord injuries (SCI) are one of the most physically and psychologically devastating injuries one can survive. Despite decades of intense research effort, robust therapeutic treatment for this catastrophic condition remains elusive. The nature of the sequelae of SCI is characterized by progressive cell death in the injury penumbra, resulting in further neurological impairments. The intricate relationship between the vascular and nervous systems has become increasingly evident in many aspects of both normal physiology, and various pathological conditions, including SCI. Vascular abnormalities play a central role in the propagation of secondary damage after SCI. The aim of this thesis is to further the understanding of the vascular changes that occur after acute SCI. The endogenous expression of three angiogenic proteins: Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2) and Angiogenin will be examined after acute traumatic SCI. In the first study, the concentration of these proteins will be measured in a temporal series of cerebrospinal fluid (CSF) samples after human SCI. In the second study, the relative protein expression of Ang1 and Ang2 will be characterized in rat spinal cord after SCI. In human, Ang1 in CSF is not significantly different from non-SCI values after the initial spike at 24 hours post-SCI. Ang2 in CSF shows a delayed but persistent increase through the first 5 days post-SCI. In contrast, Ang1 in rat spinal cord decreases as early as 2 hours post-SCI, while low molecular weight Ang2 increases dramatically after SCI, from 2 hours to 3 days post-injury, peaking with a 13-fold elevation at 24 hours post-injury. These findings represent the first description of these proteins in the acute SCI setting in human CSF and rat spinal cord. The sustained elevation of Ang2 illustrates a possible mechanism by which reported vascular dysfunction and increases in blood-spinal cord-barrier (BSCB) permeability occurs after SCI. The patterns of change reported between the two studies may allude to the feasibility of using CSF as a biological proxy to future investigations into the biochemical events which occur in the spinal cord after SCI, and guide the development of pharmacologic treatments for this devastating condition.

Text

2012-06-28

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/42577

Zoology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/