Intrathecal decompression versus epidural decompression in the treatment of severe spinal cord injury in rat model: a randomized, controlled preclinical research

Abstract Background In the setting of severe spinal cord injury (SCI), there is no markedly efficacious clinical therapeutic regimen to improve neurological function. After epidural decompression, as is shown in animal models, the swollen cord against non-elastic dura and elevation of intrathecal pressure may be the main causes of aggravated neurologic function. We performed an intrathecal decompression by longitudinal durotomy to evaluate the neuroprotective effect after severe SCI by comparing with epidural decompression. Methods Eighty-four adult male Sprague-Dawley rats were assigned to three groups: sham group (group S), epidural decompression (group C), and intrathecal decompression group (group D). A weight-drop model was performed at T9. The Basso-Beattie-Bresnahan (BBB) score was used to evaluate neurological function. Animals were sacrificed at corresponding time points, and we performed pathohistological examinations including HE staining and immunohistochemical staining (IHC) of glial fibrillary acidic protein (GFAP), neurocan, and ED1 at the epicenter of injured cords. Finally, the lesions were quantitatively analyzed by SPSS 22.0. Results The mortality rates were, respectively, 5.55 % (2/36) and 13.9 % (5/36) in groups C and D, and there was no significant difference between groups C and D (P = 0.214). Compared with epidural decompression, intrathecal decompression could obviously improve BBB scores after SCI. HE staining indicated that more white matter was spared, and fewer vacuoles and less axon degradation were observed. The expression peak of GFAP, neurocan, and ED1 occurred at an earlier time and was down-regulated in group D compared to group C. Conclusions Our findings based on rat SCI model suggest that intrathecal decompression by longitudinal durotomy can prompt recovery of neurological function, and this neuroprotective mechanism may be related to the down-regulation of GFAP, neurocan, and ED1.http://deepblue.lib.umich.edu/bitstream/2027.42/134548/1/13018_2016_Article_369.pd

An optofluidic mechanical system for elasticity measurement of thin biological tissues

As dura mater has an anisotropic fibrous structure and exists under wet and dynamic stretching conditions in the brain, its mechanical properties have not yet been properly investigated. Here we developed a fluid-assisted mechanical system integrated with a photonic sensor and a pressure sensor in order to measure the elasticity of the dura mater. Porcine dura mater sample was loaded as a stretched diaphragm into a liquid chamber to mimic the in vivo condition. Increasing the flow rate of saline solution into the chamber swelled and deformed the dura mater. The micron-scale deflection of the dura mater was optically detected by the photonic sensor. Fluid pressure and deflection values were then used to calculate the elastic modulus. The average elastic modulus of the porcine dura mater was 31.14 MPa. We further measured the elasticity of a well-known material to further validate the system. We expect that this optofluidic system developed in this study will be useful to measure the elasticity of a variety of thin biological tissues.close1

Intrathecal recombinant human 4-sulfatase reduces accumulation of glycosaminoglycans in dura of mucopolysaccharidosis VI cats

IntroductionMucopolysaccharidosis VI (MPS-VI) is caused by a deficiency in N-acetylgalactosamine-4-sulfatase activity, resulting in lysosomal accumulation of partially degraded glycosaminoglycans (GAGs). Compressive myelopathy in early-onset MPS-VI patients has been partly attributed to thickening of the dura mater following engorgement with GAG. In this study, we therefore tested whether the dural abnormalities could be prevented in a feline model of the disorder.ResultsAll intrathecal injections (IT-INJs) were well tolerated. MPS-VI cats treated with IT-INJ of recombinant human N-acetylgalactosamine-4-sulfatase (rhASB) exhibited reduced vacuolation in the dural fibroblasts, diminished levels of sulfated-N-acetylhexosamine (HNAc(+S)) in the cerebrospinal fluid (CSF) and no hind-limb paresis. Serum anti-rhASB antibodies remained low in MPS-VI cats treated with intravenous enzyme replacement therapy (IV-ERT) and increased slightly in normal cats treated with IT-INJ of rhASB alone. Anti-rhASB antibodies in CSF remained undetectable.DiscussionThese data indicate that repeated IT-INJ of rhASB can safely prevent GAG storage in MPS-VI dura.MethodsCats were assigned to three groups: (i) receiving weekly IV-ERT of rhASB from birth plus six monthly IT-INJs of rhASB from age 2 months; (ii) receiving six monthly IT-INJs of vehicle; or (iii) untreated. Additional normal cats received five fortnightly IT-INJs of rhASB or vehicle alone.Dyane Auclair, John Finnie, Steven U. Walkley, Joleen White, Timothy Nielsen, Maria Fuller, Alphonsus Cheng, Charles A. O'Neill and John J. Hopwoo