Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury

Abstract

<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel–treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H &amp; E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells).</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel–treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel–treated group. There was a decreased presence of inflammatory cells in the HA hydrogel–treated group. No axonal or neuronal regeneration was observed.</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>The results of these experiments show that HA hydrogel had a neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.</jats:p></jats:sec>

Three-dimensional hyaluronic acid hydrogel-based models for in vitro human iPSC-derived NPC culture and differentiation

“…Previous studies also showed that HA with high molecular weight was an essential organizational and structural component in the native brain ECM and had neuroprotective effects. 71,72 However, no discernible neurite outgrowth was generated in our Me-HA hydrogels. Instead, single hiPSC-NPCs spontaneously migrated and accumulated in dispersive sphere-like circular islands.…”

High molecular weight form of hyaluronic acid reduces neuroinflammatory response in injured sciatic nerve via the intracellular domain of CD44

“…A rat model of sciatic nerve crush is commonly used to study the cellular and molecular mechanisms in the peripheral nerve, 30 reported that HMW-HA has neuroprotective, 31,32 antioxidants, 33 and antiinflammatory 7,34 properties, which is believed that a variety of pharmacological actions of HMW-HA might contribute to its beneficial effect on axonal regeneration by suppressing the neuroinflammatory response. Even though our results showed the beneficial effect of HMW-HA on the injured sciatic nerve, data regarding the molecular mechanisms were limited in the current study.…”

Hierarchically aligned fibrin nanofiber hydrogel accelerated axonal regrowth and locomotor function recovery in rat spinal cord injury

“…[8][9][10] To mimic the stiffness of native nerve extracellular matrix (ECM), a variety of hydrogels with mechanical properties that can be tuned to be similar to those of native nerve tissue have been investigated as ideal candidates for spinal cord regeneration, showing positive roles in inducing stem cell neurogenic differentiation in vitro and axonal regrowth in vivo with significant and long-lasting motor functional recovery. [11][12][13][14][15][16][17][18][19] Unfortunately, most of these hydrogels are isotropic in architecture and lack oriented topography. Spinal cord tissue, especially the white matter that is composed of well-aligned axon tracts, has hierarchically oriented tissue structures ranging from a single neural axon to nerve fibers.…”