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Expression of hyaluronidase-4 in a rat spinal cord hemisection model.

ABSTRACT: STUDY DESIGN:Examination of hyaluronidase-4 (Hyal-4) expression in a rat spinal cord hemisection model. PURPOSE:To determine the status of Hyal-4 expression after hemisection of the spinal cord, and the relationship between its expression and that of chondroitin sulfate proteoglycans (CSPGs). OVERVIEW OF LITERATURE:CSPGs are expressed at the site of spinal cord injury and inhibit axon regeneration. Administration of exogenous chrondroitinase ABC (ChABC), derived from bacteria, digested CSPGs and promoted axonal regrowth. Using a rat hemisection model, we have demonstrated peak CSPGs levels at by 3 weeks after injury but then decreased spontaneously. Could there be an endogenous enzyme similar to ChABC in the spinal cord? It has been suggested that Hyal-4 is involved in CSPG degradation. METHODS:A rat hemisection model was prepared and spinal cord frozen sections were prepared at 4 days and 1, 2, 3, 4, 5, and 6 weeks post-cordotomy and stained for CSPGs and Hyal-4 and subjected to Western blotting. RESULTS:CSPGs appeared at the injury site at 4 days after hemisection, reached a peak after 3 weeks, and then decreased. Hyal-4 was observed around the injury site from 4 days after cordotomy and increased until after 5-6 weeks. Double staining showed Hyal-4 around CSPGs. Western blotting identified a band corresponding to Hyal-4 from 4 days after hemisection. CONCLUSIONS:Hyal-4 was expressed in a rat hemisection model in areas surrounding CSPGs, and as its peak was delayed compared with that of CSPGs. These results suggest the involvement of Hyal-4 in the digestion of CSPGs.

SUBMITTER: Tachi Y

PROVIDER: S-EPMC4330222 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Expression of hyaluronidase-4 in a rat spinal cord hemisection model.

Tachi Yoshiyuki Y Okuda Tetsuhito T Kawahara Norio N Kato Nobuo N Ishigaki Yasuhito Y Matsumoto Tadami T

Asian spine journal 20150213 1

<h4>Study design</h4>Examination of hyaluronidase-4 (Hyal-4) expression in a rat spinal cord hemisection model.<h4>Purpose</h4>To determine the status of Hyal-4 expression after hemisection of the spinal cord, and the relationship between its expression and that of chondroitin sulfate proteoglycans (CSPGs).<h4>Overview of literature</h4>CSPGs are expressed at the site of spinal cord injury and inhibit axon regeneration. Administration of exogenous chrondroitinase ABC (ChABC), derived from bacter ...[more]

PMID: 25705329

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Project description:Acute spinal cord injury is a devastating injury that may lead to loss of independent function. Stem-cell therapies have shown promise; however, a clinically efficacious stem-cell therapy has yet to be developed. Functionally, endothelial progenitor cells induce angiogenesis, and neural stem cells induce neurogenesis. In this study, we explored using a multimodal therapy combining endothelial progenitor cells with neural stem cells encapsulated in a bioactive biomimetic hydrogel matrix to facilitate stem cell-induced neurogenesis and angiogenesis in a rat hemisection spinal cord injury model.DesignLaboratory experimentation.SettingUniversity laboratory.SubjectsFemale Fischer 344 rats.InterventionsThree groups of rats: 1) control, 2) biomimetic hydrogel therapy, and 3) combined neural stem cell, endothelial progenitor cell, biomimetic hydrogel therapy underwent right-sided spinal cord hemisection at T9-T10. The blinded Basso, Beattie, and Bresnahan motor score was obtained weekly; after 4 weeks, observational histologic analysis of the injured spinal cords was completed.Measurements and main resultsBlinded Basso, Beattie, and Bresnahan motor score of the hind limb revealed significantly improved motor function in rats treated with combined neural stem cell, endothelial progenitor cell, and biomimetic hydrogel therapy (p < 0.05) compared with the control group. The acellular biomimetic hydrogel group did not demonstrate a significant improvement in motor function compared with the control group. Immunohistochemistry evaluation of the injured spinal cords demonstrated de novo neurogenesis and angiogenesis in the combined neural stem cell, endothelial progenitor cell, and biomimetic hydrogel therapy group, whereas, in the control group, a gap or scar was found in the injured spinal cord.ConclusionsThis study demonstrates proof of concept that multimodal therapy with endothelial progenitor cells and neural stem cells combined with a bioactive biomimetic hydrogel can be used to induce de novo CNS tissue in an injured rat spinal cord.

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Expression of hyaluronidase-4 in a rat spinal cord hemisection model.

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Expression of hyaluronidase-4 in a rat spinal cord hemisection model.

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