elastin and Spinal-Cord-Injuries

The effects of human amniotic fluid stem cell (hAFSC) transplantation on bladder function and molecular changes in spinal cord-injured (SCI) rats were investigated. Four groups were studied: sham and SCI plus phosphate-buffered saline (SCI + PBS), human embryonic kidney 293 (HEK293) cells, and hAFSCs transplantation. In SCI + PBS rat bladders, cystometry showed increased peak voiding pressure, voiding volume, bladder capacity, residual volume, and number of non-voiding contractions, and the total elastin/collagen amount was increased but collagen concentration was decreased at days 7 and 28. Immunoreactivity and mRNA levels of IGF-1, TGF-β1, and β3-adrenoceptor were increased at days 7 and/or 28. M2 immunoreactivity and M3 mRNA levels of muscarinic receptor were increased at day 7. M2 immunoreactivity was increased, but M2/M3 mRNA and M3 immunoreactivity levels were decreased at day 28. Brain derived-neurotrophic factor mRNA was increased, but immunoreactivity was decreased at day 7. HEK293 cell transplantation caused no difference compared to SCI + PBS group. hAFSCs co-localized with neural cell markers and expressed BDNF, TGF-β1, GFAP, and IL-6. The present results showed that SCI bladders released IGF-1 and TGF-β1 to stimulate elastin and collagen for bladder wall remodelling, and hAFSC transplantation improved these changes, which involved the mechanisms of BDNF, muscarinic receptors, and β3-adrenoceptor expression.

Topics: Amniotic Fluid; Animals; Collagen; Elastin; Female; HEK293 Cells; Humans; Microscopy, Confocal; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Spinal Cord Injuries; Stem Cell Transplantation; Urinary Bladder; Urinary Bladder Diseases

High-thoracic or cervical spinal cord injury (SCI) is associated with several critical clinical conditions related to impaired cerebrovascular health, including: 300-400% increased risk of stroke, cognitive decline and diminished cerebral blood flow regulation. The purpose of this study was to examine the influence of high-thoracic (T3 spinal segment) SCI on cerebrovascular structure and function, as well as molecular markers of profibrosis. Seven weeks after complete T3 spinal cord transection (T3-SCI, n = 15) or sham injury (Sham, n = 10), rats were sacrificed for either middle cerebral artery (MCA) structure and function assessments via ex vivo pressure myography, or immunohistochemical analyses. Myogenic tone was unchanged, but over a range of transmural pressures, inward remodelling occurred after T3-SCI with a 40% reduction in distensibility (both P < 0.05), and a 33% reduction in vasoconstrictive reactivity to 5-HT trending toward significance (P = 0.09). After T3-SCI, the MCA had more collagen I (42%), collagen III (24%), transforming growth factor β (47%) and angiotensin II receptor type 2 (132%), 27% less elastin as well as concurrent increased wall thickness and reduced lumen diameter (all P < 0.05). Sympathetic innervation (tyrosine hydroxylase-positive axon density) and endothelium-dependent dilatation (carbachol) of the MCA were not different between groups. This study demonstrates profibrosis and hypertrophic inward remodelling within the largest cerebral artery after high-thoracic SCI, leading to increased stiffness and possibly impaired reactivity. These deleterious adaptations would substantially undermine the capacity for regulation of cerebral blood flow and probably underlie several cerebrovascular clinical conditions in the SCI population.

Topics: Animals; Axons; Collagen; Elastin; Fibrosis; Male; Middle Cerebral Artery; Rats; Rats, Wistar; Receptor, Angiotensin, Type 2; Spinal Cord Injuries; Transforming Growth Factor beta; Tyrosine 3-Monooxygenase; Vasoconstriction

To determine the inhibitory effects of pudendal nerve stimulation (5 Hz) on bladder overactivity at the early stage of spinal cord injury (SCI) in dogs, and to explore the possible effects on delayed progression of bladder fibrosis after SCI.. The study was performed using six dogs with spinal cord transection at the T9–T10 level. Group 1 (three dogs) under went low-frequency electrical stimulation of the pudendal nerve 1 day after spinal cord transection. Group 2 (three dogs) underwent only spinal cord transection. All dogs underwent urodynamic examination at 1 and 3 months after SCI. The bladders were removed for histological examination of fibrosis at 3 months after SCI.. Bladder capacity and compliance were significantly increased (P<0.05) by pudendal nerve stimulation in group 1 when compared with group 2 at 1 and 3 months after SCI. Non-voiding contractions (NVCs) were inhibited in group 1 compared with group 2. Collagen fibers were significantly increased and elastic fibers were significantly decreased (P<0.05) in group 2 when compared with group 1.. Early low-frequency pudendal nerve stimulation can inhibit detrusor overactivity (DO), increase bladder capacity and delay the progression of bladder fibrosis.

Topics: Animals; Collagen; Compliance; Disease Progression; Dogs; Elastin; Electric Stimulation; Electrodes, Implanted; Fibrosis; Male; Muscle, Smooth; Pudendal Nerve; Spinal Cord Injuries; Urinary Bladder Diseases; Urinary Bladder, Overactive; Urodynamics

A key attribute missing from many current biomaterials is the ability to independently tune multiple biomaterial properties without simultaneously affecting other material parameters. Because cells are well known to respond to changes in the initial elastic modulus, degradation rate, and cell adhesivity of a biomaterial, it is critical to develop synthetic design strategies that allow decoupled tailoring of each individual parameter in order to systematically optimize cell-scaffold interactions. We present the development of a family of biomimetic scaffolds composed of chemically crosslinked, elastin-like proteins designed to support neural regeneration through a combination of cell adhesion and cell-induced degradation and remodeling. Through use of a modular protein-design strategy, a range of biomaterials is created that allows independent tuning over the initial elastic modulus, degradation rate, cell adhesivity, and neurite outgrowth. By combining these engineered proteins into composite structures, biomaterials are created with 3D patterns that emerge over time in response to cell-secreted enzymes. These dynamic 3D structures enable the delivery of multiple drugs with precise spatial and temporal resolution and also enable the design of biomaterials that adapt to changing scaffold needs.

Topics: Biocompatible Materials; Biomimetics; Cell Adhesion; Cell Physiological Phenomena; Cells; Elastin; Fibronectins; Humans; Nerve Regeneration; Neurites; Neurons; Peripheral Nervous System; Recombinant Proteins; Spinal Cord Injuries; Tissue Engineering; Tissue Plasminogen Activator; Tissue Scaffolds; Urokinase-Type Plasminogen Activator

We have demonstrated that bladder wall tissue in spinal cord injury (SCI) rats at 10 days post-injury is more compliant and accompanied by changes in material class from orthotropic to isotropic as compared to normal tissue. The present study examined the long-term effects (3-, 6-, and 10-weeks) post-SCI on the mechanical properties of bladder wall tissues, along with quantitative changes in smooth muscle orientation and collagen and elastin content. Bladder wall compliance (defined as det(F) - 1 under an equi-biaxial stress state of 100 kPa, where F is the deformation gradient tensor) was found to be significantly greater at 3- and 6-weeks (0.873 +/- 0.092 and 0.864 +/- 0.112, respectively) when compared to the normal bladders (0.260 +/- 0.028), but at 10 weeks the compliance reduced (0.389 +/- 0.061) to near that of normal bladders. This trend in mechanical compliance closely paralleled the collagen/elastin ratio. Moreover, changes in material class, assessed using a graphical technique, correlated closely with quantitative changes in smooth muscle fiber orientation. The results of the present study provide the first evidence that, while similarities exist between acute and chronic responses of the urinary bladder wall tissue to SCI, the overall alterations are distinct, result in profound and complex time dependent changes in bladder wall structure, and will lay the basis for simulations of the bladder wall disease process.

Topics: Animals; Collagen; Elastin; Female; Muscle, Smooth; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Stress, Mechanical; Time Factors; Urinary Bladder

In order to gain a deeper understanding of bladder function, it is necessary to study the time-dependent response of the bladder wall. The present study evaluated and compared the viscoelastic behaviors of normal and spinal cord injured (SCI) rat bladder wall tissue using an established rat model and planar biaxial stress relaxation tests. Bladders from normal and spinalized (3 weeks) rats were subjected to biaxial stress (either 25 or 100 kPa in each loading direction) rapidly (in 50 ms) and subsequently allowed to relax at the constant stretch levels in modified Kreb's solution (in the absence of calcium; with no smooth muscle tone) for 10,000 s. We observed slower and therefore less stress relaxation in the SCI group compared to the normal group, which varied with the stress-level. These experimental results were fitted (r2 > 0.98) to a reduced relaxation function. Furthermore, biochemical assays revealed that the collagen content of SCI rat bladders was significantly (p < 0.05) lower by 43%, while the elastin content was significantly (p < 0.001) higher by 260% than that of normal bladders. These results suggest that SCI and the associated urologic functional changes induce profound tissue remodeling, which, in turn, provided the structural basis for the alterations in the complex, time-dependent mechanical behavior of the urinary bladder wall observed in the present study.

Topics: Adaptation, Physiological; Animals; Anisotropy; Collagen; Computer Simulation; Elasticity; Elastin; Female; Models, Biological; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Stress, Mechanical; Tensile Strength; Thoracic Vertebrae; Urinary Bladder; Urinary Bladder, Neurogenic; Viscosity