Precise Delivery Into Chronic Spinal Cord Injury Syringomyelic Cysts with Magnetic Nanoparticles MRI Visualization

Abstract

BackgroundTraumatic spinal cord injury (SCI) often results in the deficiency of glia and neurons in cystic cavities. These syringomyelic cysts can prevent axonal regeneration and sprouting. Details of the mechanism of syringomyelic cyst formation are unknown and an effective treatment for overcoming syringomyelic cysts is not available.Material/MethodsTen adult female Wistar rats underwent contusion SCI modeling resulting in syringomyelic cyst formation. A novel method for locating the cysts was developed and employed. MRI safe silver needles were inserted through the erector spinae of anesthetized rats to create a stable reference point. MRI images of the rodent spine were taken with the needles in situ. This information was used to accurately locate the cyst and determine the 3-dimensional entry point coordinates for nanoparticle delivery. Nanoparticles were injected into the cyst during a primary injection of 8 ul and a secondary injection of 8 ul, to prove the procedure can be accurately repeated.ResultsNone of the rats died intra- or post-operatively. The syringomyelic cysts were accurately located with the 3-dimensional entry point coordinates. After nanoparticle delivery twice into each rat, the visualized syringomyelic cyst volume significantly decreased from 5.71±0.21 mm3 to 3.23±0.364 mm3 and to 1.48±0.722 mm3.ConclusionsThe present study describes a novel strategy for precise nanoparticle delivery into a syringomyelic cyst, using measurements obtained from MRI images. This strategy may aid in developing a new method for studying chronic spinal cord injury and a novel treatment for syringomyelic cysts.

The Role of Astrogliosis in Formation of the Syrinx in Spinal Cord Injury

“…Formation of the syrinx is reported to occur in <1-7% in patients with neurological deficits [ 25 - 27 ] and the incidence of radiological diagnosis of cavitations in SCI patients is >50% [ 28 - 30 ] indicating a considerable discrepancy, the reason for which is not clear. Post- traumatic formation of the COI is a complex and insufficiently studied process involving the transformation of a poorly defined area of hemorrhage and cellular necrosis surrounded by tissue edema [ 6 , 9 , 10 ] into a defined cystic structure, filled with fluid containing necrotic debris, red blood cells, and large numbers of phagocytic macrophages [ 6 - 8 , 11 ] with apparently simultaneous inflow of edema fluid from the surrounding spinal cord [ 9 , 10 , 31 ]. The COI is well defined 7 days post-SCI and it is delineated by a layer of progressively severe astrogliosis in the surrounding spinal cord [ 6 - 8 , 11 ].…”

The Role of Biomaterials in Peripheral Nerve and Spinal Cord Injury: A Review

“…Both PNI and SCI injuries are characterized by inadequate physical and molecular substrates to which axons can attach. In PNI, destruction of the structural collagenous membranes generates misguided and inefficient regeneration, whereas in SCI, axons are unlikely to demonstrate any growth to the cystic lesion site [11,52]. Biomaterials can offer a solution to overcome these limitations as they can be designed to mimic ECM architecture and serve as substrates onto which axons can attach.…”

The Pathogenesis of Neurotrauma Indicates Targets for Neuroprotective Therapies

“…The usefulness of in vivo MR imaging in the rodent models of neurotrauma has been demonstrated in a number of studies on the SCI [ 69 - 71 ] and TBI [ 72 - 74 ]. It needs to be, however, pointed out that the breathing movements of the thorax in the rat in the supine recumbency affect the position of the cervical and thoracic spinal cord, therefore the quality of imaging of the spinal cord.…”