Salmon fibrin treatment of spinal cord injury promotes functional recovery and density of serotonergic innervation

Abstract

The neural degeneration caused by spinal cord injury leaves a cavity at the injury site that greatly inhibits repair. One approach to promoting repair is to fill the cavity with a scaffold to limit further damage and encourage regrowth. Injectable materials are advantageous scaffolds because they can be placed as a liquid in the lesion site then form a solid in vivo that precisely matches the contours of the lesion. Fibrin is one type of injectable scaffold, but risk of infection from blood borne pathogens has limited its use. We investigated the potential utility of salmon fibrin as an injectable scaffold to treat spinal cord injury since it lacks mammalian infectious agents and encourages greater neuronal extension in vitro than mammalian fibrin or Matrigel®, another injectable material. Female rats received a T9 dorsal hemisection injury and were treated with either salmon or human fibrin at the time of injury while a third group served as untreated controls. Locomotor function was assessed using the BBB scale, bladder function was analyzed by measuring residual urine, and sensory responses were tested by mechanical stimulation (von Frey hairs). Histological analyses quantified the glial scar, lesion volume, and serotonergic fiber density. Rats that received salmon fibrin exhibited significantly improved recovery of both locomotor and bladder function and a greater density of serotonergic innervation caudal to the lesion site without exacerbation of pain. Rats treated with salmon fibrin also exhibited less autophagia than those treated with human fibrin, potentially pointing to amelioration of sensory dysfunction. Glial scar formation and lesion size did not differ significantly among groups. The pattern and timing of salmon fibrin’s effects suggest that it acts on neuronal populations but not by stimulating long tract regeneration. Salmon fibrin clearly has properties distinct from those of mammalian fibrin and is a beneficial injectable scaffold for treatment of spinal cord injury.

Effects of Biologic Scaffolds on Human Stem Cells and Implications for CNS Tissue Engineering

“…9,10 Safety concerns aside, efficacy of NSCs in CNS therapies may be enhanced by or even require co-delivery with cell-supportive materials such as ECM, which appropriately direct cell behavior, thereby inducing graft-host integration and improving functional outcomes. 4,[46][47][48] With the exception of dura mater repair, 30-32 the development and application of tissue-derived ECM scaffolds for CNS reconstruction has not been commonly described. [17][18][19][20] Minimally invasive implantation of an ECM hydrogel scaffold 4,18,20 may provide a niche-friendly microenvironment at a CNS injury site to encourage endogenous NSCs to migrate to the site, proliferate, and differentiate to replace lost neural cells and ultimately, produce functional tissue.…”

Fibrin Scaffolds Containing Ectomesenchymal Stem Cells Enhance Behavioral and Histological Improvement in a Rat Model of Spinal Cord Injury

“…The fibrin scaffolds transplanted to the sites of SCI inhibit the glial scar formation and promote nerve regeneration [Johnson et al, 2010]. Although fibrin can help the axon sprout in the SCI, the effects observed from the rodents are not satisfactory, in part due to the limited functions of fibrin on promoting axon regeneration and remyelination or inhibiting glial scar formation [Taylor et al, 2006;Sharp et al, 2012]. Enormous efforts have been made to enhance the function of fibrin scaffold.…”

Benefits of Spine Stabilization with Biodegradable Scaffolds in Spinal Cord Injured Rats

“…24,25 This protocol may influence the motor recovery of control rats, given that, it was previously described that fibrin alone promotes tissue regeneration. 26 Due to the subjectivity inherent to BBB test, the motor function of the animals was also assessed by the rotarod and OF test methods. Analysis of motor coordination, balance, motor control, and trunk stability was performed with these tests.…”