Role of the blood-spinal cord barrier in posttraumatic syringomyelia

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>Posttraumatic syringomyelia produces a significant burden of pain and neurological deficits in patients with spinal cord injury. The mechanism of syrinx formation is unknown and treatment is often ineffective. A possible explanation for syrinx formation is fluid leakage from the microcirculation in the presence of a compromised blood-spinal cord barrier (BSCB). The aim of this study was to investigate the structural and functional integrity of the BSCB in a model of posttraumatic syringomyelia.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The excitotoxic amino acid and arachnoiditis model of syringomyelia was used in 27 Sprague-Dawley rats. Structural integrity of the BSCB was assessed using immunoreactivity to endothelial barrier antigen (EBA), and loss of functional integrity was assessed by extravasation of intravascular horseradish peroxidase. Animals were studied after 3 days, or at 1, 3, 6, or 12 weeks after surgery. There were laminectomy-only and saline injection control animals for comparison at each time point.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Syrinxes formed in 16 of the 17 animals injected with excitotoxic amino acid. Loss of structural and functional integrity of the BSCB in syrinx animals was noted at all time points. Disruption of the BSCB was most dramatic in tissue adjacent to the syrinx, and in the central and dorsal gray matter. Changes in EBA expression generally corresponded with altered vascular permeability, although in the acute stages, widespread vascular permeability occurred without a corresponding decrease in EBA expression. At the later time points (3–12 weeks) EBA expression was often absent, although no vascular leakage was observed.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>This study demonstrated a prolonged structural and functional disruption of the BSCB in this model of posttraumatic syringomyelia. Loss of functional integrity of the BSCB, with fluid entering the interstitial space of the spinal cord, may contribute to initial cyst formation after spinal cord injury and subsequent enlargement of the cyst, to produce posttraumatic syringomyelia.</jats:p></jats:sec>

Aquaporin-4 Expression in Post-Traumatic Syringomyelia

“…A previous study carried out in our laboratory found that in this excitotoxic model of post-traumatic syringomyelia, the blood-spinal cord barrier (BSCB) is still impaired surrounding a syrinx cavity even at 12 weeks following the initial syrinx induction. 17 In this study, the most significant leakage of tracer across the BSCB was observed at the earlier time-points (three days and one week). It is possible that at three days and one week, AQP4 levels were insufficient to remove fluid that was leaking from the surrounding vasculature.…”

“…There is evidence that the blood-spinal cord barrier is impaired in an animal model of post-traumatic syringomyelia even three months after the initial cyst formation. 17 The water channel protein aquaporin-4 (AQP4) facilitates transmembrane water movement in the central nervous system. AQP4 has been implicated in a wide range of pathological conditions involving abnormal water accumulation within the brain and spinal cord.…”

Editorial: Posttraumatic syringomyelia

“…8,12,13,17,20 However, syrinx enlargement over time is common. 4,16 Evidence suggests that PTS is increasingly recognized with the greater use of MR imaging in recent years. 19 Clinical observations and animal models suggest that the development of PTS is associated with the formation of an initial lesion due to secondary pathological SCI mechanisms (excitotoxic cell death and apoptosis) as well as subarachnoid scarring and alteration of CSF fluid flow and pressure dynamics causing increased CSF flow into the spinal cord (Fig.…”

“…For example, once a cyst starts to expand in the cord parenchyma, it can damage the surrounding blood-spinal barrier and allow additional fluid from the vasculature to enter the cyst. 4 Such tissue damage can also alter fluid clearance mechanisms, including aquaporin expression and function. 5 In addition to fluid inflow and outflow, tissue properties are also likely to be important in PTS development.…”

Direct-trauma model of posttraumatic syringomyelia with a computer-controlled motorized spinal cord impactor

“…6,26,41,45 Based on these models, researchers have obtained important data, such as the nature of fluid flow into and out of syrinx cavities, the integrity of the blood-spinal cord barrier, the presence of neural progenitor cells, and aqua porin 4 expression around syrinx cavities. 7,14,41,43 However, all the existing animal models have their shortcomings, and concerns regarding their applicability to humans remain. The ideal posttraumatic syrinx model is yet to be developed, but its characteristics should include the following: 1) excellent reproducibility and reliability of expanding syrinx production; 2) a mechanism of initial injury similar to that of human spinal cord injuries; 3) samples that histologically resemble postmortem human samples; 4) an extracanalicular location of syrinx cavities; and 5) progressive enlargement and neurological deficits similar to those in the human condition.…”