The Effect of Tissue Inhibitor of Metalloproteinases on Scar Formation after Spinal Cord Injury.

Spinal cord injury (SCI) often results in permanent loss of motor and sensory function. After SCI, the blood-spinal cord barrier (BSCB) is disrupted, causing the infiltration of neutrophils and macrophages, which secrete several kinds of cytokines, as well as matrix metalloproteinases (MMPs). MMPs are proteases capable of degrading various extracellular matrix (ECM) proteins, as well as many non-matrix substrates. The tissue inhibitor of MMPs (TIMP)-1 is significantly upregulated post-SCI and operates via MMP-dependent and MMP-independent pathways. Through the MMP-dependent pathway, TIMP-1 directly reduces inflammation and destruction of the ECM by binding and blocking the catalytic domains of MMPs. Thus, TIMP-1 helps preserve the BSCB and reduces immune cell infiltration. The MMP-independent pathway involves TIMP-1's cytokine-like functions, in which it binds specific TIMP surface receptors. Through receptor binding, TIMP-1 can stimulate the proliferation of several types of cells, including keratinocytes, aortic smooth muscle cells, skin epithelial cells, corneal epithelial cells, and astrocytes. TIMP-1 induces astrocyte proliferation, modulates microglia activation, and increases myelination and neurite extension in the central nervous system (CNS). In addition, TIMP-1 also regulates apoptosis and promotes cell survival through direct signaling. This review provides a comprehensive assessment of TIMP-1, specifically regarding its contribution to inflammation, ECM remodeling, and scar formation after SCI.

Comparison of nylon, vicryl, and fibrin glue for nerve grafting in rats.

OBJECTIVES: For nerve injuries, not amendable to tensionless epineural coaptation of the nerve, autografts are the preferred treatment. Although absorbable sutures are not recommended for nerve repair, there is no evidence that non-absorbable sutures are superior to absorbable sutures. This study aims to assess the effectiveness of non-absorbable monofilament nylon sutures, absorbable monofilament vicryl sutures, and fibrin glue when used for nerve grafting. METHODS: Lewis rats (N = 32) were subjected to a sciatic nerve transection and randomly assigned to a group: graft with Nylon, graft with Vicryl, graft with Fibrin Glue, or no graft. Motor function, sensory function, and thermal pain were assessed during a 12-week recovery period, and immunohistochemistry was used to assess macrophage response. RESULTS: At 12 weeks, the Vicryl and Nylon groups had significantly larger ankle angles at to lift off, which is a measure of motor function, compared to injured controls (p < 0.05). Grafted rats displayed no difference in thermal response but hypersensitivity to mechanical stimuli compared to the uninjured hindlimb. The Nylon, Vicryl, and Fibrin Glue groups all had significantly less atrophy of the gastrocnemius muscle compared to injured controls (p < 0.0001). In the Fibrin Glue group, 3/9 grafts did not incorporate. The Nylon group had significantly less (p = 0.0004) axon growth surrounding the suture holes compared to the Vicryl group. There were no differences in the axon counts, motor neurons, or sensory neurons between all grafted rats. CONCLUSIONS: These results demonstrate that vicryl sutures work just as well as nylon for nerve recovery after injury and grafting.

Gait analysis in swine, sheep, and goats after neurologic injury: a literature review.

Medical research on neurologic ailments requires representative animal models to validate treatments before they are translated to human clinical trials. Rodents are the predominant animal model used in neurological research despite limited anatomic and physiologic similarities to humans. As a result, functional testing designed to assess locomotor recovery after neurologic impairment is well established in rodent models. Comparatively, larger, more clinically relevant models have not been as well studied. To achieve similar locomotor testing standardization in larger animals, the models must be accessible to a wide array of researchers. Non-human primates are the most relevant animal model for translational research, however ethical and financial barriers limit their accessibility. This review focuses on swine, sheep, and goats as large animal alternatives for transitional studies between rodents and non-human primates. The objective of this review is to compare motor testing and data collection methods used in swine, sheep, and goats to encourage testing standardization in these larger animal models. The PubMed database was analyzed by searching combinations of swine, sheep, and goats, neurologic injuries, and functional assessments. Findings were categorized by animal model, data collection method, and assessment design. Swine and sheep were used in the majority of the studies, while only two studies were found using goats. The functional assessments included open pen analysis, treadmill walking, and guided free walking. Data collection methods included subjective behavioral rating scales and objective tools such as pressure-sensitive mats and image-based analysis software. Overall, swine and sheep were well-suited for a variety of assessment designs, with treadmill walking and guided free walking offering the most consistency across multiple trials. Data collection methods varied, but image-based gait analysis software provided the most robust analysis. Future studies should be conducted to standardize functional testing methods after neurologic impairment in large animals.