Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells From Different Donors on Spinal Cord Injury in Mice

Spinal cord injury (SCI) is caused by an external force, leading to severe dysfunction of the limbs below the injured segment. The inflammatory response plays a vital role in the prognosis of SCI. Human umbilical cord mesenchymal stem cell (hUCMSC) transplantation can promote repair of SCI by reducing the inflammatory response. We previously showed that hUCMSCs from 32 donors had different inhibitory abilities on BV2 cell proliferation. In this study, three experimental groups were established, and the mice were injected with different lines of hUCMSCs. Hind limb motor function, hematoxylin-eosin (H&E) staining, immunohistochemistry, Western blot (WB), qualitative real-time polymerase chain reaction (qRT-PCR), and RNA sequencing and correlation analysis were used to investigate the effects of hUCMSC transplantation on SCI mice and the underlying mechanisms. The results showed that the therapeutic effects of the three hUCMSC lines were positively correlated with their inhibitory abilities of BV2 cell proliferation rates in vitro. The MSC_A line had a better therapeutic effect on improving the hind limb motor function and greater effect on reducing the expression of glial fibrillary acidic protein (Gfap) and ionized calcium binding adaptor molecule 1 (Iba1) and increasing the expression of neuronal nuclei (NeuN). Differentially expressed genes including Zbtb16, Per3, and Hif3a were probably the key genes involved in the protective mechanism by MSC_A after nerve injury. qRT-PCR results further verified that Zbtb16, Per3, and Hif3a expressions reduced by SCI could be reversed by MSC_A application. These results suggest that the effect of hUCMSCs transplantation on acute SCI depends on their inhibitory abilities to inflammation reaction after nerve injury, which may help to shape future use of hUCMSCs combined with improving the effectiveness of clinical transformation.

Administration of Particulate Oxygen Generators Improves Skeletal Muscle Contractile Function Following Ischemia-Reperfusion Injury in the Rat Hind Limb

Extended tourniquet application, often associated with battlefield extremity trauma, can lead to severe ischemia-reperfusion (I/R) injury in skeletal muscle. Particulate oxygen generators (POGs) can be directly injected into tissue to supply oxygen to attenuate the effects of I/R injury in muscle. The goal of this study was to investigate the efficacy of a sodium percarbonate (SPO)-based POG formulation in reducing ischemic damage in a rat hind limb during tourniquet application. Male Lewis rats were anesthetized and underwent tourniquet application for 3 hours, at a pressure of 300 mmHg. Shortly after tourniquet inflation animals received intramuscular injections of either 0.2 mg/mL SPO with catalase (n=6) or 2.0 mg/mL SPO with catalase (n=6) directly into the tibialis anterior (TA) muscle. An additional Tourniquet-Only group (n=12) received no intervention. Functional recovery was monitored using in vivo contractile testing of the hind limb at 1-, 2-, and 4-weeks post-injury. By the 4 week time point, the Low Dose POGs group continued to show improved functional recovery (85% of baseline) compared to the Tourniquet-Only (48%) and High Dose POG (56%) groups. In short, the Low Dose POGs formulation appeared, at least in part, to mitigate the impact of ischemic tissue injury, thus improving contractile function following tourniquet application. Functional improvement correlated with maintenance of larger muscle fiber cross sectional area, and the presence of fewer fibers containing centrally located nuclei. As such, POGs represent a potentially attractive therapeutic solution for addressing I/R injuries associated with extremity trauma.

Case Report: Successful Management of a Compressive Intraspinal Coccidioides Species Granuloma in a Cat

A 9-year-old, neutered male, domestic shorthair cat from Arizona, was presented for evaluation of a 7-day history of hind limb paraparesis that progressed to paraplegia. There was no history of respiratory abnormalities. Neurologic examination supported localization of a T3-L3 myelopathy. Computed tomography (CT) revealed an expansile widening of the spinal canal dorsal to L4 associated with a strongly contrast-enhancing mass. Moreover, CT series of the thorax revealed a diffuse miliary pulmonary pattern, as well as tracheobronchial, sternal, and cranial mediastinal lymphadenomegaly. Transthoracic lung lobe and sternal lymph node fine needle aspiration revealed pyogranulomatous inflammation with Coccidioides spp. spherules and endospores. A suspected diagnosis of spinal coccidioidomycosis was made; fluconazole (10.9 mg/kg PO q12h) treatment was initiated, and decompressive neurosurgery was performed. The granuloma was removed en bloc and histopathology revealed marked, chronic-active, pyogranulomatous myelitis with intralesional Coccidioides spp. spherules with endosporulation. Serum anti-Coccidioides spp. antibody titer results revealed a negative IgM and a positive IgG (1:4). The cat was treated with fluconazole for 445 days and examined at various time points, with the last examination 2 years after initial presentation. The cat returned to full ambulation with only mild functional deficits of the right hind limb. In conclusion, this report documents the diagnosis, treatment, and long-term follow up of a cat with a compressive Coccidioides spp. spinal cord granuloma. This case highlights the importance of including coccidioidomycosis as a differential diagnosis for cats with peracute hindlimb paraplegia that have lived in or traveled to regions where Coccidioides spp. is endemic, and demonstrates the potential for a good long-term outcome with decompressive neurosurgery and antifungal therapy.

Multiple Undifferentiated Pleomorphic Sarcoma (Malignant Fibrous Histiocytoma) with Extradural Involvement in a 7-Year-Old Labrador Retriever

A 7-year-old castrated male Labrador retriever was referred for evaluation of progressive hind limb paresis of 4 weeks’ duration. On computed tomography and magnetic resonance imaging examination, masses were found in several regions including the lung, right kidney, and peritoneum. Additionally, an extradural mass at the region of T13–L1 was identified, which is assumed to related to the chief complaint, progressive hind limb paresis. With the consent of the owner, a dorsal laminectomy was performed to remove the mass and surrounding tissues for the palliation of the hind limb paresis. Hematoxylin and eosin staining and immunohistochemical examination revealed the mass to be consistent with an undifferentiated (high-grade) pleomorphic sarcoma. The patient presented with recurrence of the hind limb paresis, respiratory discomfort, and urinary incontinence. The owner declined treatment and the dog was euthanized. Systemic metastasis was confirmed on postmortem microscopic examination. To the authors’ knowledge, this is the first report describing multiple undifferentiated high-grade pleomorphic sarcoma with extradural involvement developing into the vertebral canal through the intervertebral space, resulting in spinal damage, in a dog.

Traumatic exungulation in cattle: ten cases (1993–2018)

OBJECTIVE To describe clinical findings, treatments, and outcomes for cattle with complete traumatic exungulation. ANIMALS 10 bovines. PROCEDURES Record databases of 2 teaching hospitals were searched to identify cattle treated for traumatic exungulation between January 1993 and December 2018. Information about signalment, clinical signs and findings, treatment, and outcome was extracted from the records or obtained by telephone communication with the owner. RESULTS Records for 5 bulls, 4 heifers, and 1 cow with a median age of 2 years (range, 1 day to 10 years) and weight of 379.1 kg (range, 30 to 909.1 kg) were reviewed. Duration of clinical signs ranged from ≤ 24 hours to 3.5 days. Five of 7 animals had a lameness score > 3/5. Complete exungulation occurred in 6 medial digits (3 hind limbs and 3 forelimbs) and 5 lateral digits (1 hind limb and 4 forelimbs); 1 calf had complete exungulation of both digits of a forelimb. Treatments included bandaging (n = 9), antimicrobials (9), anti-inflammatories (8), hoof block application to the adjacent digit (7), regional anesthesia (6), cast application (4), curettage of the third phalanx (3), regional antimicrobial perfusion (1), and local application of antimicrobial-impregnated beads (1). All 7 cattle with long-term (≥ 9 months) information available returned to their intended function; 6 had no residual lameness, and 3 required regular corrective trimming of the affected digit. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested the prognosis for long-term survival and return to intended function is fair to good for cattle with complete exungulation.

Deficiency of MMP-10 Aggravates the Diseased Phenotype of Aged Dystrophic Mice

Matrix metalloproteinases (MMPs) have been implicated in the progression of muscular dystrophy, and recent studies have reported the role of MMP-10 in skeletal muscle pathology of young dystrophic mice. Nevertheless, its involvement in dystrophin-deficient hearts remains unexplored. Here, we aimed to investigate the involvement of MMP-10 in the progression of severe muscular dystrophy and to characterize MMP-10 loss in skeletal and cardiac muscles of aged dystrophic mice. We examined the histopathological effect of MMP-10 ablation in aged mdx mice, both in the hind limb muscles and heart tissues. We found that MMP-10 loss compromises survival rates of aged mdx mice, with skeletal and cardiac muscles developing a chronic inflammatory response. Our findings indicate that MMP-10 is implicated in severe muscular dystrophy progression, thus identifying a new area of research that could lead to future therapies for dystrophic muscles.