Extracellular matrix (ECM) deposition after central nervous system (CNS) injury leads to inhibitory scarring in mammals, whereas it facilitates axon regeneration in the zebrafish. However, the molecular basis of these different fates is not understood. Here, we identify small leucine-rich proteoglycans (SLRPs) as a causal factor in regeneration failure. We demonstrate that the SLRPs Chondroadherin, Fibromodulin, Lumican, and Prolargin are enriched in human, but not zebrafish, CNS lesions. Targeting SLRPs to the zebrafish injury ECM inhibits axon regeneration and functional recovery. Mechanistically, we find that SLRPs confer structural and mechanical properties to the lesion environment that are adverse to axon growth. Our study reveals SLRPs as previously unknown inhibitory ECM factors in the human CNS that impair axon regeneration by modifying tissue mechanics and structure.
Biomechanical properties drive the functioning of cells and tissue. Measurement of such properties in the clinic is quite challenging, however. Optical coherence elastography is an emerging technique in this field that can measure the biomechanical properties of the tissue. Unfortunately, such systems have been limited to benchtop configuration with limited clinical applications. A truly portable system with a flexible probe that could probe different sample sites with ease is still missing. In this work, we report a portable optical coherence elastography system based on a flexible common path optical fiber probe. The common path approach allows us to reduce the undesired phase noise in the system by an order of magnitude less than the standard non-common path systems. The flexible catheter makes it possible to probe different parts of the body with ease. Being portable, our system can be easily transported to and from the clinic. We tested the efficacy of the system by measuring the mechanical properties of the agarbased tissue phantoms. We also measured the mechanical properties (Young's Modulus) of the human skin at different sites. The measured values for the agar phantom and the skin were found to be comparable with the previously reported studies. Ultra-high phase stability and flexibility of the probe along with the portability of the whole system makes an ideal combination for the faster clinical adoption of the optical coherence elastography technique.
The measurement of the biomechanical properties of the skin is of great interest since these properties play an important role in the development of several diseases such as skin cancer and systemic sclerosis. In this direction, several diagnostic tools have been developed to analyze the mechanical properties of the skin. Optical coherence elastography (OCE) is one of the emerging imaging techniques used for the characterization of the mechanical properties of the tissue quantitatively. In systemic sclerosis patients, the measurement of the mechanical properties of the deeper skin layers is desirable compared to the superficial layers. There are several variants of OCE that exist, but it is still not clear which method is more suitable for the measurement of the mechanical properties of the deeper tissue. In this work, we tested three common methods, the pulsed excitation method, the continuous wave excitation method, and the resonant frequency method, for the measurement of the mechanical properties of the deeper layers in the tissue. We found out that the pulsed wave excitation method provides the most reliable measurements in the shortest possible time compared to the other two methods.
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