Vascular Disruption and the Role of Angiogenic Proteins After Spinal Cord Injury
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REVIEW ARTICLE
Vascular Disruption and the Role of Angiogenic Proteins After Spinal Cord Injury Michelle T. L. Ng & Anthea T. Stammers & Brian K. Kwon
Received: 31 July 2011 / Revised: 20 September 2011 / Accepted: 25 September 2011 / Published online: 13 October 2011 # Springer Science+Business Media, LLC 2011
Abstract Spinal cord injuries (SCI) can result in devastating paralysis, for which there is currently no robustly efficacious neuroprotective/neuroregenerative treatment. When the spinal cord is subjected to a traumatic injury, the local vasculature is disrupted and the blood–spinal cord barrier is compromised. Subsequent inflammation and ischemia may then contribute to further secondary damage, exacerbating neurological deficits. Therefore, understanding the vascular response to SCI and the molecular elements that regulate angiogenesis has considerable relevance from a therapeutic standpoint. In this paper, we review the nature of vascular damage after traumatic SCI and what is known about the role that angiogenic proteins—angiopoietin 1 (Ang1), angiopoietin 2 (Ang2) and angiogenin—may play in the subsequent response. To this, we add recent work that we have conducted in measuring these proteins in the cerebrospinal fluid (CSF) and serum after acute SCI in human patients. Intrathecal catheters were installed in 15 acute SCI patients within 48 h of injury. CSF and serum samples were collected over the following 3–5 days and analysed for Ang1, Ang2 and angiogenin protein levels using a standard ELISA technique. This represents the first description of the endogenous expression of these proteins in an acute human SCI setting. M. T. L. Ng : A. T. Stammers : B. K. Kwon (*) International Collaboration on Repair Discoveries (ICORD), Blusson Spinal Cord Centre, University of British Columbia, 818 West 10th Avenue, Vancouver, BC, Canada V5Z 1M9 e-mail: [email protected] B. K. Kwon Combined Neurosurgical and Orthopaedic Spine Program (CNOSP), Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada
Keywords Spinal cord injury . Angiogenesis . Blood–spinal cord barrier . Angiopoietin . Angiogenin
Introduction Each year, over 10,000 North Americans suffer acute and permanent paralysis after sustaining a traumatic spinal cord injury (SCI) [46]. Not only is an SCI one of the most physically disabling and psychologically devastating traumas that an individual can survive, the socioeconomic burden is enormous. Estimates of the annual medical and rehabilitative expenses are in the $1 million range for individuals with high cervical cord paralysis [176]. Whilst historically this has been an injury of the youth, an ageing population prone to suffering cervical cord injuries after falls has altered the demographics of SCI, with a second peak of traumatic SCI appearing in the elderly population aged 65 and above [191]. The poor neurologic prognosis for SCI has prompted the development of a plethora of therapeutic strategies, many of which have shown promise in the laboratory setting [122, 123, 185].
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