Aquaporin-4 expression and modulation in a rat model of post-traumatic syringomyelia.

Aquaporin-4 (AQP4) has been implicated in post-traumatic syringomyelia (PTS), a disease characterised by the formation of fluid-filled cysts in the spinal cord. This study investigated the expression of AQP4 around a mature cyst (syrinx) and the effect of pharmacomodulation of AQP4 on syrinx size. PTS was induced in male Sprague-Dawley rats by computerized spinal cord impact and subarachnoid kaolin injection. Immunofluorescence of AQP4 was carried out on mature syrinx tissue 12 weeks post-surgery. Increased AQP4 expression corresponded to larger, multiloculated cysts (R2 = 0.94), yet no localized changes to AQP4 expression in perivascular regions or the glia limitans were present. In a separate cohort of animals, at 6 weeks post-surgery, an AQP4 agonist (AqF026), antagonist (AqB050), or vehicle was administered daily over 4 days, with MRIs performed before and after the completion of treatment. Histological analysis was performed at 12 weeks post-surgery. Syrinx volume and length were not altered with AQP4 modulation. The correlation between increased AQP4 expression with syrinx area suggests that AQP4 or the glia expressing AQP4 are recruited to regulate water movement. Given this, further investigation should examine AQP4 modulation with dose regimens at earlier time-points after PTS induction, as these may alter the course of syrinx development.

Compositional effects of clay-fly ash geopolymers on the sorption process of lead and zinc.

Because long-term leachate penetration through a hydraulic barrier is unavoidable, active-passive liners are widely used to mitigate the migration of potential contaminants. Geopolymerization represents a viable method for metals removal, which simultaneously improves the properties of local clay to compensate for the lack of suitable soil in the design of active-passive liners. This study investigated how clay-fly ash geopolymers enhance the sorption of divalent lead [Pb(II)] and divalent zinc [Zn(II)] from leachate compared with an untreated clay. Two clay-fly ash geopolymers were synthesized from the mixtures containing 50 and 60% fly ash to the total solid mass and then activated by 10 M NaOH solutions. The influence of Na/fly ash ratios and activator content was also examined. The results indicate that a fly ash-based geopolymer could be a simple solution to increase the sorption capacity of local clay. A lower ratio of Na/fly ash and activator content, resulting in a higher porosity, led to a better performance for metal removal. According to the results of sorption isotherms and batch experiments, Pb(II) and Zn(II) exhibit different sorption behaviors affected by the compositions of synthesized clay-fly ash geopolymers, which could be adjusted to reach a proper sorption capacity. The results of the kinetic study also show that the heterogeneous matrix of the clay-fly ash geopolymers with different porosities led to mutual cooperation between reaction and diffusion-controlled steps for metal removal.

Lateral Lumbar Interbody Fusion at L4-5: A Morphometric Analysis of Psoas Anatomy and Cage Placement.

BACKGROUND: The ventral elevation (VE) of the psoas from the vertebral column as seen on axial magnetic resonance imaging has been suggested as a preclusion of a safe working zone for lateral lumbar interbody fusion (LLIF) at L4-5. However, no quantitative study has been conducted to verify this. METHODS: L4-5 LLIF was attempted using 22-mm wider cages whenever feasible over 18-mm standard cages in a consecutive series of 62 patients. The degree of VE of the psoas measured from the anterior border of the L5 endplate and the anteroposterior cage position measured from the posterior vertebral border to the center of the cage normalized to the anteroposterior width of the L5 endplate were recorded on axial images. RESULTS: LLIF was successfully performed in all cases despite 18 patients (29%) harboring elevated psoas. Standard cage was applied in 25 (40%) patients due to nerve proximity. Wider cage was applied equally frequent in both elevated (56%) and nonelevated groups (60%, P = 0.78). The mean cage position was found to be 0.54 ± 0.10 (standard deviation) and no difference was detected between the elevated (0.54 ± 0.11) and nonelevated (0.53 ± 0.10, P = 0.78) groups. Multivariate analyses and receiver operating characteristic analysis demonstrated that VE displayed low performance in predicting the choice of cages. CONCLUSIONS: LLIF is feasible in patients with ventrally elevated psoas, and the choice of cages does not appear to be influenced by the location of the psoas. Relying on the rising psoas sign on magnetic resonance imaging as a case selection criterion may unjustly exclude patients from LLIF.

Abnormalities in spinal cord ultrastructure in a rat model of post-traumatic syringomyelia.

BACKGROUND: Syringomyelia is a serious complication of spinal cord trauma, occurring in approximately 28% of spinal cord injuries. Treatment options are limited and often produce unsatisfactory results. Post-traumatic syringomyelia (PTS) is presumably related to abnormalities of cerebrospinal fluid (CSF) and interstitial fluid hydrodynamics, but the exact mechanisms are unknown. METHODS: Transmission electron microscopy (TEM) was used to investigate in detail the interfaces between fluid and tissue in the spinal cords of healthy Sprague-Dawley rats (n = 3) and in a rat model of PTS (n = 3). PTS was induced by computer-controlled impact (75 kDyn) to the spinal cord between C6 and C8, followed by a subarachnoid injection of kaolin to produce focal arachnoiditis. Control animals received a laminectomy only to C6 and C7 vertebrae. Animals were sacrificed 12 weeks post-surgery, and spinal cords were prepared for TEM. Ultra-thin spinal cord sections at the level of the injury were counterstained for structural anatomy. RESULTS: Spinal cords from animals with PTS displayed several abnormalities including enlarged perivascular spaces, extracellular edema, cell death and loss of tissue integrity. Additionally, alterations to endothelial tight junctions and an abundance of pinocytotic vesicles, in tissue adjacent to syrinx, suggested perturbations to blood-spinal cord barrier (BSCB) function. CONCLUSIONS: These findings support the hypothesis that perivascular spaces are important pathways for CSF flow into and out of the spinal cord, but also suggest that fluid may enter the cord through vesicular transport and an altered BSCB.

Effect of extradural constriction on CSF flow in rat spinal cord.

BACKGROUND: Fluid homeostasis in the central nervous system (CNS) is essential for normal neurological function. Cerebrospinal fluid (CSF) in the subarachnoid space and interstitial fluid circulation in the CNS parenchyma clears metabolites and neurotransmitters and removes pathogens and excess proteins. A thorough understanding of the normal physiology is required in order to understand CNS fluid disorders, including post-traumatic syringomyelia. The aim of this project was to compare fluid transport, using quantitative imaging of tracers, in the spinal cord from animals with normal and obstructed spinal subarachnoid spaces. METHODS: A modified extradural constriction model was used to obstruct CSF flow in the subarachnoid space at the cervicothoracic junction (C7-T1) in Sprague-Dawley rats. Alexa-Fluor 647 Ovalbumin conjugate was injected into the cisterna magna at either 1 or 6 weeks post-surgery. Macroscopic and microscopic fluorescent imaging were performed in animals sacrificed at 10 or 20 min post-injection. Tracer fluorescence intensity was compared at cervical and thoracic spinal cord levels between control and constriction animals at each post-surgery and post-injection time point. The distribution of tracer around arterioles, venules and capillaries was also compared. RESULTS: Macroscopically, the fluorescence intensity of CSF tracer was significantly greater in spinal cords from animals with a constricted subarachnoid space compared to controls, except at 1 week post-surgery and 10 min post-injection. CSF tracer fluorescence intensity from microscopic images was significantly higher in the white matter of constriction animals 1 week post surgery and 10 min post-injection. At 6 weeks post-constriction surgery, fluorescence intensity in both gray and white matter was significantly increased in animals sacrificed 10 min post-injection. At 20 min post-injection this difference was significant only in the white matter and was less prominent. CSF tracer was found predominantly in the perivascular spaces of arterioles and venules, as well as the basement membrane of capillaries, highlighting the importance of perivascular pathways in the transport of fluid and solutes in the spinal cord. CONCLUSIONS: The presence of a subarachnoid space obstruction may lead to an increase in fluid flow within the spinal cord tissue, presenting as increased flow in the perivascular spaces of arterioles and venules, and the basement membranes of capillaries. Increased fluid retention in the spinal cord in the presence of an obstructed subarachnoid space may be a critical step in the development of post-traumatic syringomyelia.

A radiographic analysis of cage positioning in lateral transpsoas lumbar interbody fusion.

Direct Lumbar Interbody Fusion (DLIF) and eXtreme Lateral Interbody Fusion (XLIF) are the most common surgical platforms available for performing transpsoas spinal fusion but no study has been carried out to compare them. We evaluated 21 DLIF and 22 XLIF cage positions by measuring the distance between the posterior vertebral border and the centre of the cage normalised to the midsagittal length of the inferior end plate. We found that DLIF cages were significantly more anteriorly located than XLIF (0.65 vs 0.52, p = 0.001) at L4-5, suggesting that XLIF would permit implantation of wider cages than DLIF.

The ultrastructure of spinal cord perivascular spaces: Implications for the circulation of cerebrospinal fluid.

Perivascular spaces play a pivotal role in the exchange between cerebrospinal and interstitial fluids, and in the clearance of waste in the CNS, yet their precise anatomical components are not well described. The aim of this study was to characterise the ultrastructure of perivascular spaces and their role in the transport of fluid, in the spinal cord of healthy rats, using transmission electron microscopy. The distribution of cerebrospinal fluid tracers injected into the subarachnoid space was studied using light, confocal and electron microscopy. Perivascular spaces were found around arterioles and venules, but not capillaries, throughout the spinal cord white and grey matter. They contained fibroblasts and collagen fibres, and were continuous with the extracellular spaces of the surrounding tissue. At 5 min post injection, tracers were seen in the subarachnoid space, the peripheral white matter, the perivascular spaces, basement membranes, extracellular spaces of the surrounding tissue, and surprisingly, in the lumen of blood vessels, suggesting trans-vascular clearance. These findings point out an unrecognised outflow pathway for CNS fluids, with potential implications for volume regulation in health and disease states, but also clinically for the detection of CNS-derived biomarkers in plasma, the immune response and drug pharmacokinetics.

Longitudinal measurements of syrinx size in a rat model of posttraumatic syringomyelia.

OBJECTIVE Syringomyelia pathophysiology is commonly studied using rodent models. However, in vivo studies of posttraumatic syringomyelia have been limited by the size of animals and lack of reliable noninvasive evaluation techniques. Imaging the rat spinal cord is particularly challenging because the spinal cord diameter is approximately 1-3 mm, and pathological lesions within the spinal cord parenchyma are even smaller. The standard technique has been histological evaluation, but this has its limitations. The aim of the present study was to determine whether syrinx size could be reliably measured using a preclinical high-field MRI animal system in a rat model of posttraumatic syringomyelia. METHODS The authors used an existing rat model of posttraumatic syringomyelia, which was created using a controlled pneumatic compression device to produce the initial spinal cord injury, followed by a subarachnoid injection of kaolin to produce arachnoiditis. T2-weighted MRI was performed on each animal using a 9.4-T scanner at 7, 10, and 13 weeks after injury. Animals were killed and syrinx sizes were calculated from in vivo MRI and histological studies. RESULTS MRI measurements of syrinx volume and length were closely correlated to histological measurements across all time points (Pearson product moment correlation coefficient r = ± 0.93 and 0.79, respectively). CONCLUSIONS This study demonstrates that high-field T2-weighted MRI can be used to measure syrinx size, and data correlate well with syrinx size measured using histological methods. Preclinical MRI may be a valuable noninvasive technique for tracking syrinx formation and enlargement in animal models of syringomyelia.