A 50-step walking test for analysis of recovery after decompressive surgery for thoracolumbar disc herniation in dogs.

BACKGROUND: Despite its importance, there is no agreed definition of recovery of ambulation in dogs with spinal cord injury. OBJECTIVES: To validate a new walking test in dogs recovering from thoracolumbar spinal cord injury. ANIMALS: Two hundred twenty-four dogs weighing <20 kg: 120 normally ambulatory dogs, plus 104 dogs undergoing decompressive surgery for acute thoracolumbar intervertebral disc herniation. METHODS: Prospective cohort studies. The distance each freely-ambulatory dog walked during 50 step cycles was regressed on ulna length. For each postsurgical dog, we recorded when the calculated 50-step distance was completed without falling, or their inability to complete this distance by 4 months or more after surgery. Bayesian analysis compared outcomes for presurgical neurologic categories; association of recovery with several preoperative variables was explored using logistic and time-to-event regression. RESULTS: For control dogs, 50-step distance (m) = 1.384 × ulnar length (cm) + 2.773. In postsurgical dogs, the 50-step test provided decisive evidence that deep pain-negative dogs were less likely to recover ambulation than dogs with intact pain perception (12/29 recovered vs 71/75; Bayes factor [BF] = 5.9 × 106 ) and, if they did recover, it took much longer (median 91 days vs median 14 days; BF = 1.5 × 103 ). Exploratory analysis suggested that presurgical neurologic status (subhazard ratio [SHR] = 0.022; P < .001) and duration of presurgical anesthesia (SHR = 0.740; P = .04) were associated with rapidity of recovery. CONCLUSIONS AND CLINICAL IMPORTANCE: This straightforward 50-step walking test provides robust data on ambulatory recovery well-suited to large scale pragmatic trials on treatment of thoracolumbar spinal cord injury in dogs.

Clinical and Histopathological Findings of Hemorrhagic Progressive Myelomalacia after Lumbar Tap in 2 Dogs: Case Report.

Bichon frise (1) and Boxer (2), both with epileptic seizures, underwent lumbar taps for cerebrospinal fluid collection. After the procedure, the first dog became paraplegic, and the second dog did not recover from anesthesia and remained in a coma. Both dogs were euthanatized 12 h after the examination. The dogs were diagnosed with idiopathic epilepsy and fibrillar astrocytoma, respectively, after postmortem examination. They were also diagnosed with progressive myelomalacia, involving C1-C5 until the L4-S3 spinal segments. Since it was not possible to attribute the development of myelomalacia to the primary diseases observed, the lumbar tap likely caused this severe spinal cord injury. These reports highlight myelomalacia as a possible complication of lumbar taps.

Evaluation of body surface temperature variations in dogs affected by spinal cord injuries during physiotherapy exercise in a water treadmill.

The aim this study was to evaluate variation in body surface temperature (BST) in healthy and spinal cord injured (SCI) dogs, and to outline temperature variation at rest (T0), during (T1) and after (T2) water-treadmill physiotherapy sessions in SCI using infrared thermography (IRT). Sixty-seven dogs of different sex, breed, body weight and age were enrolled: 14 healthy dogs and 53 dogs affected by disc pathologies. The study examined three regions of interest (ROIs): the total image of the spine (IMAGE), the spinal cord area from 1st thoracic vertebra to the last lumbar vertebra (AR01) and the surgery wound or spinal cord lesion area (AR02). Significant BST variations between healthy and SCI were reported in T°max and T°max-min (ΔT) values in IMAGE (P < 0.05). In SCI group, AR01 and AR02 assessment showed an increase in temperature ate the sited of the injured area and adjacent body structures. In SCI, a significant effect of water-treadmill exercise in AR01 and AR02 was reported. In fact, both AR01 and AR02 reported higher BST (T°max, T°mean, T°min and ΔT) during the physical exercise (T1), representing the response to physical activity of the spine vascularization, muscles and column contiguous tissues. Furthermore, in T2, the same areas reported a significant lower BST (T°max, T°mean, and ΔT), related to a decrease in tissue inflammation on the target area of the water treadmill physiotherapy. This study highlights how IRT can detect BST variations associated with injured areas. In addition, IRT revealed a positive effect of water-treadmill exercise on the injured spinal cord areas, thus it could be a viable non-invasive and rapid method to support both clinical examination and assessment of the effectiveness of medical treatment in SCI.

The Long-Term Efficacy Study of Multiple Allogeneic Canine Adipose Tissue-Derived Mesenchymal Stem Cells Transplantations Combined With Surgery in Four Dogs With Lumbosacral Spinal Cord Injury.

Severe lumbosacral pain, paraparesis or paraplegia, and urinary incontinence are common but frustrating problems in dogs with lumbosacral spinal cord injury (SCI). The surgical interventions including stabilization and decompression may not restore satisfying neurological functions in severe SCI. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) show benefits in immunomodulation, anti-inflammation, and promotion of axonal growth and remyelination, and also display efficacy in several diseases in veterinary medicine. In this report, four dogs presented with fracture of sacrum vertebrae or fracture of seventh lumbar and lumbosacral displacement after road traffic accidents. The clinical signs include lumbosacral pain (4/4), paraparesis (3/4), paraplegia (1/4), and urinary incontinence (4/4). All dogs were treated by surgical decompression with or without stabilization 1 to 7 weeks after trauma. Allogeneic canine Ad-MSCs (cAd-MSCs) were injected locally on nerve roots through the surgical region in all dogs. One dose of intravenous transplantation and 4 doses of local transplantation were also performed within 8 weeks after the surgery separately. All dogs showed significant neurological improvements with normal ambulatory ability (4/4) and urinary control (3/4) 3 months after the surgery and the first cAd-MSCs transplantation. No side effect was related to multiple cAd-MSCs transplantations during 6 months monitoring in all dogs. In conclusion, multiple cAd-MSCs transplantations could be a recommended treatment combined with surgery in dogs with lumbosacral SCI.

Circulating neutrophil activation in dogs with naturally occurring spinal cord injury secondary to intervertebral disk herniation.

OBJECTIVE: To investigate the time course of circulating neutrophil priming and activity in dogs with spinal cord injury secondary to intervertebral disk herniation that undergo decompressive surgery. ANIMALS: 9 dogs with spinal cord injury and 9 healthy dogs (controls). PROCEDURES: For dogs with spinal cord injury, blood samples were collected on the day of hospital admission and 3, 7, 30, and 90 days after injury and decompressive surgery. A single blood sample was collected from the control dogs. Flow cytometry analysis was performed on isolated neutrophils incubated with antibody against CD11b and nonfluorescent dihydrorhodamine 123, which was converted to fluorescent rhodamine 123 to measure oxidative burst activity. RESULTS: Expression of CD11b was increased in dogs with spinal cord injury 3 days after injury and decompressive surgery, relative to day 7 expression. Neutrophils expressed high oxidative burst activity both 3 and 7 days after injury and decompressive surgery, compared with activity in healthy dogs. CLINICAL RELEVANCE: For dogs with spinal cord injury, high CD11b expression 3 days after injury and decompressive surgery was consistent with findings for rodents with experimentally induced spinal cord injury. However, the high oxidative burst activity 3 and 7 days after injury and decompressive surgery was not consistent with data from other species, and additional studies on inflammatory events in dogs with naturally occurring spinal cord injury are needed.

Intramuscular tetanus neurotoxin reverses muscle atrophy: a randomized controlled trial in dogs with spinal cord injury.

BACKGROUND: Motor symptoms of spinal cord injury (SCI) considerably impair quality of life and are associated with a high risk of secondary diseases. So far, no pharmacological treatment is available for these symptoms. Therefore, we conducted a randomized, double-blinded, placebo-controlled study in dogs with spontaneous SCI due to disc herniation to test whether a reduction of spinal inhibitory activity by intramuscular injections of tetanus neurotoxin (TeNT) alleviates motor symptoms such as muscle atrophy or gait function. METHODS: To this end, 25 dogs were treated with injections of either TeNT or placebo into their paretic hindlimb muscles. Effects of TeNT on muscle thickness were assessed by ultrasound, while effects on gait function were measured using the modified functional scoring system in dogs. RESULTS: Four weeks after the TeNT injections, muscle thickness of the gluteus medius muscle (before median 1.56 cm [inter-quartile range {IQR} 1.34-1.71 cm] and after median 1.56 cm [IQR 1.37-1.85 cm], P-value 0.0133) as well as of the rectus femoris muscle (before median 0.76 cm [IQR 0.60-0.98 cm] and after median 0.93 cm [IQR 0.65-1.05 cm], P-value 0.0033) significantly increased in the TeNT group. However, there was no difference in gait function between the TeNT and placebo groups. The treatment was well tolerated by all dogs without any signs of generalized tetanus symptoms or any spreading of effects beyond the lumbar level of the injected hindlimbs. CONCLUSIONS: With regard to the beneficial effects on muscle thickness, intramuscular injections of TeNT represent the first pharmacological approach that focally reverses muscle atrophy in SCI. Moreover, the study data support the safety of this treatment when TeNT is used at low dose.

Vertebrectomia total e estabilização com pinos e polimetilmetacrilato como tratamento para luxação entre vértebras torácicas em cão ­ relato de caso / Total vertebrectomy and stabilization with pins and polymethylmethacrylate as treatment for thoracic vertebral luxation in a dog - case report

As lesões decorrentes de atropelamento são as principais causas de fraturas e luxações vertebrais, ocasionando graus variáveis de injúrias vertebrais e medulares. O presente trabalho tem como objetivo relatar a ocorrência de lesão traumática em coluna vertebral de cão sem raça definida, com quatro anos de idade, resultando em luxação T11-12, com exposição de T11 e secção medular, estando o paciente paraplégico, com sinais de lesão em neurônio motor superior e ausência de nocicepção profunda em membros pélvicos. O tratamento de escolha foi a vertebrectomia de T11, associada ao alinhamento de T10-12 com introdução de pinos e fixação com polimetilmetacrilato (PMMA) associado à ceftriaxona. Em decorrência de lesão na pleura parietal no trans-cirúrgico, optou-se pela toracostomia para introdução de tubo torácico, o qual permaneceu no paciente por quatro dias. No pós-operatório, o paciente apresentou recuperação satisfatória, sendo recomendado aos tutores a confecção de cadeira de rodas a fim de facilitar sua locomoção. A técnica mostrou-se satisfatória para minimizar as infecções passíveis de ocorrência em fraturas expostas, bem como melhorar a qualidade de vida do paciente, evitando-se dores crônicas.

Injuries resulting from being run over are the leading causes of vertebral fractures and dislocations, causing varying vertebral and spinal injuries. The present study aims to report the occurrence of traumatic injury to the spine of a mixed breed dog, aged four years, resulting in a T11-12 dislocation, with T11 exposure and spinal section, with the patient showing paraplegia, signs of an upper motor neuron lesion and absence of deep nociception in pelvic limbs. The treatment of choice was T11 vertebrectomy, associated with the alignment of T10-12 with the introduction of pins and fixation with polymethylmethacrylate (PMMA) associated with ceftriaxone. Due to a lesion in the parietal pleura during the surgery, thoracostomy was chosen to introduce a chest tube, which remained in the patient for four days. In the postoperative period, the patient presented a satisfactory recovery, and it was recommended that tutors make a wheelchair to facilitate their mobility. The technique proved to be satisfactory for minimizing infections that could occur in open fractures and improving the patient's quality of life, avoiding chronic pain.

Effect of combined intrathecal/intravenous injection of bone marrow derived stromal cells in platelet-rich plasma on spinal cord injury in companion animals.

Background: Companion animals are prone to spinal cord injuries commonly associated with severe locomotor and sensory complications, which can escalate to a state of irreversible paralysis. Stem cell therapies propose a hope for treating spinal cord injuries via differentiation into neurons and associated glial cells, halting the immune attacks, inhibiting apoptosis and necrosis, and secretion of neurotrophic factors that stimulate the regeneration process. Aim: The study aims to evaluate the use of autologous bone marrow derived stromal cells in platelet-rich plasma carrier for selected clinical cases having chronic spinal cord injuries in dogs and cats via a one-time combined intrathecal/intravenous injection. Methods: Cells were injected in five dogs and three cats suffering from disc protrusion leading to spinal cord injury and in thosewho did not respond to conventional treatment during a clinical trial. Results: Results indicated that the transplanted cells led to the restoration of the weight bearing locomotor function and spinal reflexes in a period less than 90 days with physical rehabilitation. The treatment showed minor changes in the magnetic resonance images of extruded discs. Conclusion: This study concluded that the combined intrathecal/intravenous injection of bone marrow stromal cells is a safe and promising procedure for treating chronic spinal cord injuries in companion animals.

Collagen/heparin sulfate scaffold combined with mesenchymal stem cells treatment for canines with spinal cord injury: A pilot feasibility study.

BACKGROUND: Due to endogenous neuronal deficiency and glial scar formation, spinal cord injury (SCI) often leads to irreversible neurological loss. Accumulating evidence has shown that a suitable scaffold has important value for promoting nerve regeneration after SCI. Collagen/heparin sulfate scaffold (CHSS) has shown effect for guiding axonal regeneration and decreasing glial scar deposition after SCI. The current research aimed to evaluate the utility of the CHSSs adsorbed with mesenchymal stem cells (MSCs) on nerve regeneration, and functional recovery after acute complete SCI. METHODS: CHSSs were prepared, and evaluated for biocompatibility. The CHSSs adsorbed with MSCs were transplanted into these canines with complete SCI. RESULTS: We observed that MSCs had good biocompatibility with CHSSs. In complete transverse SCI models, the implantation of CHSS co-cultured with MSCs exhibited significant improvement in locomotion, motor evoked potential, magnetic resonance imaging, diffusion tensor imaging, and urodynamic parameters. Meanwhile, nerve fibers were markedly improved in the CHSS adsorbed with MSCs group. Moreover, we observed that the implantation of CHSS combined with MSCs modulated inflammatory cytokine levels. CONCLUSIONS: The results preliminarily demonstrated that the transplantation of MSCs on a CHSS could improve the recovery of motor function after SCI. Thus, implanting the MSCs-laden CHSS is a promising combinatorial therapy for treatment in acute SCI.

Lumbar Myelopathy Caused by Multiple Cartilaginous Exostoses in a Dog.

A 6-months-old male mixed-breed dog was admitted to the veterinary hospital with lameness in the right pelvic limb, proprioceptive ataxia, and suspected spinal cord injury in the lumbosacral segment. Upon palpation, firm nodules were noted on the bony surface of the thoracic and pelvic limbs, ribs, vertebrae, and tail. The radiographic study showed nodules of low radiopacity with well-defined limits and smooth contours, one of which was overlapping the fifth lumbar vertebra. Given the clinical presentation indicative of spinal cord injury, the animal was subjected to hemilaminectomy for nodular resection. Histopathological examination of the biopsy enabled the diagnosis of osteochondroma. The clinical follow up after surgery showed improvement in walking, despite persistent monoparesis in the right pelvic limb. The radiographic study in association with clinical and histopathological exams allowed the diagnosis and monitoring of the lesions.

Outcomes of extensive hemilaminectomy with durotomy on dogs with presumptive progressive myelomalacia: a retrospective study on 34 cases.

BACKGROUND: Progressive myelomalacia (PMM) is a fatal complication of progressive ascending and descending necrosis of the spinal cord after acute spinal cord injury. A recent study suggested that extensive hemilaminectomy with durotomy (EHLD) at the intramedullary T2-hyperintense region which performed immediately after magnetic resonance imaging (MRI) improved the survival rate in dogs with presumptive PMM. The objective of this retrospective study was to evaluate the effects of EHLD on halting the progression of PMM in dogs presumptively diagnosed with PMM which had the interval between MRI and surgery. RESULTS: Thirty-four dogs with presumptive PMM which had undergone EHLD with the delay following MRI examination (range, 0 to 3 days) were included. The cranial side of EHLD was set depending on the delay time after MRI, MRI findings, neurological examination and intraoperative macroscopic appearance. Two weeks after surgery, the perioperative survival rate was 97% (33/34). During follow-up with a median time period of 82.5 weeks (range, 0-290 weeks), the postoperative survival rate was 91% (31/34). At the end of the follow-up period, 31 out of 34 dogs were alive without severe postoperative complications while the remaining 2 dogs died from causes not directly attributable to the surgery. There was no improvement in the pelvic limb function of all dogs. CONCLUSIONS: EHLD appears to be effective in halting the progression of presumptive PMM and preventing morbidity even in dogs which had the interval between MRI and EHLD. Our algorithm of determining the range of EHLD may enable to set the appropriate ranges of EHLD in the cases which develop signs consistent with PMM after MRI examination.

Efficacy of autologous bone marrow mononuclear cell transplantation in dogs with chronic spinal cord injury.

Background: Spinal cord injury (SCI) is relatively common in dogs and is a devastating condition involving loss of sensory neurons and motor neurons. However, the main clinical protocol for the management of SCI is surgery to decompress and stabilize the vertebra. Cell transplantation therapy is a very promising strategy for the treatment of chronic SCI, but extensive preclinical and clinical research work remains. Aim: The aim of this study is to confirm the effect of bone marrow-derived mononuclear cell (BM-MNC) transplantation for chronic SCI in dogs. Methods: We tested the treatment efficiency of chronic SCI in 12 dogs using BM-MNC transplantation. Neurological evaluation used the Texas Spinal Cord Injury Scale (TSCIS). Concurrently, we characterized the transplanted cells by evaluation using quantitative real-time polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay. Result: All dogs had a pre-transplantation TSCIS score of 0. Two animals did not show any improvement in their final TSCIS scores. The remaining 10 dogs (83.4%) achieved improvement in the final TSCIS scores. Five of them (41.7%) regained ambulatory function with a TSCIS score greater than 10. We determined that canine BM-MNCs expressed hepatocyte growth factor (HGF) mRNA at higher levels than other cytokines, with significant increases in HGF levels in cerebrospinal fluid within 48 hours after autologous BM-MNC transplantation into the subarachnoid space of the spinal dura matter in dogs. Conclusions: BM-MNC transplantation may be effective for at least some cases of chronic SCI.

Stem Cell Conditioned Medium Treatment for Canine Spinal Cord Injury: Pilot Feasibility Study.

Spinal cord injury (SCI) involves nerve damage and often leads to motor, sensory and autonomic dysfunctions. In the present study, we have designed a clinical protocol to assess the feasibility of systemic delivery of allogenic canine bone marrow tissue-derived mesenchymal stem cell conditioned medium (BMMSC CM) to dogs with SCI. Four client-owned dogs with chronic SCI lasting more than six months underwent neurological and clinical evaluation, MRI imaging and blood tests before being enrolled in this study. All dogs received four intravenous infusions with canine allogenic BMMSC CM within one month. Between the infusions the dogs received comprehensive physiotherapy, which continued for three additional months. No adverse effects or complications were observed during the one, three and six months follow-up periods. Neither blood chemistry panel nor hematology profile showed any significant changes. All dogs were clinically improved as assessed using Olby locomotor scales after one, three and six months of BMMSC CM treatment. Furthermore, goniometric measurements revealed partial improvement in the range of joint motion. Bladder function improved in two disabled dogs. We conclude that multiple delivery of allogenic cell-derived conditioned medium to dogs with chronic SCI is feasible, and it might be clinically beneficial in combination with physiotherapy.

Long-term postoperative pain evaluation in dogs with thoracolumbar intervertebral disk herniation after hemilaminectomy.

BACKGROUND: Chronic neuropathic pain is a common complication in people with spinal cord injury (SCI) but has not been investigated in dogs. OBJECTIVE: To determine the reliability of measuring spinal mechanical sensory thresholds (MSTs) in dogs and to compare MSTs of healthy dogs and dogs with SCI caused by acute thoracolumbar intervertebral disk extrusion after hemilaminectomy over a 1-year period. STUDY DESIGN: Prospective study. ANIMALS: Thirty-two healthy and 40 SCI dogs. METHODS: Dogs were divided into group 1 (healthy Dachshunds), group 2 (healthy dogs including several breeds), and SCI group. The MSTs were measured using algometry at an incision (thoracolumbar) and control site. Dogs in group 1 were tested once; those in group 2 were tested for 5 consecutive days; and SCI dogs were tested on days 7, 14, 28, 42, 180, and 365 postoperatively. The MSTs were compared among days in healthy and SCI dogs and between SCI and healthy dogs using mixed effect models. P < .05 was considered significant. RESULTS: At the incision site of SCI dogs, MST was significantly lower than in healthy dogs for 42 days postoperatively, but not subsequently. However, 4/27 dogs had control site MST below the reference range 1 year after surgery. CONCLUSIONS AND CLINICAL IMPORTANCE: Mechanical sensory thresholds normalize by 6 months after surgery in most dogs with SCI. Approximately 15% of SCI dogs may develop chronic neuropathic pain. Improving long-term pain assessment of SCI dogs is important for offering treatment options and advising owners.

Association between anesthesia duration and outcome in dogs with surgically treated acute severe spinal cord injury caused by thoracolumbar intervertebral disk herniation.

BACKGROUND: Retrospective research recently identified a possible relationship between duration of surgery and outcome in severely affected dogs treated surgically for acute thoracolumbar intervertebral disk herniation (TL-IVDH). HYPOTHESIS: That increased duration of surgery is associated with poorer outcome in dogs with absent pain perception treated surgically for TL-IVDH. ANIMALS: Two hundred ninety-seven paraplegic dogs with absent pain perception surgically treated for acute TL-IVDH. METHODS: Retrospective cohort study. Medical records of 5 institutions were reviewed. Inclusion criteria were paraplegia with absence of pain perception, surgical treatment of TL-IVDH, and 1-year postoperative outcome (ambulatory: yes or no). Canine data, outcome, and surgery and total anesthesia duration were retrieved. RESULTS: In this study, 183/297 (61.6%) dogs were ambulatory within 1 year, 114 (38.4%) dogs failed to recover, including 74 dogs (24.9%) euthanized because of progressive myelomalacia. Median anesthesia duration in dogs that regained ambulation within 1 year of surgery (4.0 hours, interquartile range [IQR] 3.2-5.1) was significantly shorter than those that did not (4.5 hours, IQR 3.7-5.6, P = .01). Multivariable logistic regression demonstrated a significant negative association between both duration of surgery and total anesthesia time and ambulation at 1 year when controlling for body weight and number of disk spaces operated on. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings support a negative association between increased duration of anesthesia and outcome in this group of dogs. However, the retrospective nature of the data does not imply a causal relationship.

Extended durotomy to treat severe spinal cord injury after acute thoracolumbar disc herniation in dogs.

OBJECTIVE: To report recovery of ambulation of dogs treated with extended thoracolumbar durotomy for severe spinal cord injury caused by intervertebral disc herniation. STUDY DESIGN: Descriptive cohort. ANIMALS: Twenty-six consecutive paraplegic dogs presented with loss of deep pain sensation after acute thoracolumbar intervertebral disc herniation. METHODS: Each dog underwent routine diagnostic assessment and surgery for removal of extradural herniated intervertebral disc, followed by a four-vertebral body length durotomy centered on the herniated disc. Each dog was followed up until it was able to walk 10 steps without assistance or until 6 months after surgery. RESULTS: Sixteen of 26 dogs recovered to walk unaided (all but one also recovered fecal and urinary continence), and six dogs did not; four dogs were lost to follow-up. One dog was euthanized because of signs consistent with progressive myelomalacia. There was no evidence of detrimental effects of durotomy within the period of study. Using Bayesian analysis, we found a point estimate of successful outcome of 71% with 95% credible interval from 52% to 87%. CONCLUSION: Extended durotomy seemed to improve the outcome of dogs in our case series without increase in morbidity. CLINICAL SIGNIFICANCE: Extended durotomy appears safe and may improve the outcome of dogs with severe thoracolumbar mixed contusion and compressive injuries associated with acute intervertebral disc extrusion.

Can Paraplegia by Disruption of the Spinal Cord Tissue Be Reversed? The Signs of a New Perspective.

Central nervous system (CNS) trauma is often related to tissue loss, leading to partial or complete disruption of spinal cord function due to neuronal death. Although generally irreversible, traditional therapeutic efforts, such as physical therapy exercises, are generally recommended, but with a poor or reduced improvement of the microenvironment, which in turn stimulates neuroplasticity and neuroregeneration. Mesenchymal stem cells (MSCs) have paracrine, immunomodulatory, and anti-inflammatory effects. Here we use stem cells to see if they can promote not only physical but also the functional regeneration of neuronal tissue in dogs with CNS traumas. Two dogs, one with chronic spinal cord injury and one with subacute spinal cord injury, underwent infusion of autologous MSCs in association with physiotherapy. The two treatments in combination were able to partially or completely recover the dog's walking movement again. The treatment of MSCs in association with physical therapy improved the microenvironment, which could be evidence of a paradigm shift that the CNS is not capable of functional regeneration after aggressive traumas. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1812-1820, 2020. © 2019 American Association for Anatomy.

Combination of stem cells from deciduous teeth and electroacupuncture for therapy in dogs with chronic spinal cord injury: A pilot study.

Spinal cord injury (SCI) is a serious condition that causes profound economic and emotional impact in human patients and companion animal owners. It has been shown that the neurogenic effects of the stem cells are enhanced when combined with electroacupuncture (EA) in rodent models of SCI. To determine the safety and feasibility of combining transplantation of allogenic stem cells derived from canine exfoliated deciduous teeth (SCED) and EA in dogs with chronic spinal cord injury a canine pilot clinical study was conducted. A total of 16 individuals ranging from 5 to 11 years at 3 to 18 months of injury were investigated and randomly assigned to 4 experimental groups (SCED, EA, SCED + EA, control). Mild neurological and functional improvements were seen in all 4 groups. There was no clinical progression or mortality of the cases occurred in a follow up of 7 months after procedure. The study shows that SCED transplantation and electroacupuncture were feasible, safe and potentially beneficial. However Long-term patient monitoring is necessary to rule out any delayed side effects and assess any further improvements.

Nanoparticle-Based Imaging of Clinical Transplant Populations Encapsulated in Protective Polymer Matrices.

A recent clinical trial proves that autologous olfactory mucosal cell (OMC) transplantation improves locomotion in dogs with naturally occurring spinal injuries comparable to human lesions. However, not all dogs respond to the treatment, likely due to the transplantation procedures involving injections of cell suspensions that are associated with cell death, uneven cell distribution, and cell washout. Encapsulating cells in protective hydrogel matrices offers a tissue engineering solution to safely achieve 3D growth of viable transplant cells for implantation into injury sites, to improve regenerative outcomes. It is shown for the first time that canine OMCs (cOMCs) can be propagated with high viability in 3D collagen matrices. Further, a method to incorporate cOMCs pre-labeled with clinical-grade iron oxide nanoparticles into the constructs is described. Intraconstruct labeled cells are visualized using magnetic resonance imaging, offering substantial promise for in vivo tracking of cOMCs delivered in protective matrices.

miR-136-5p Regulates the Inflammatory Response by Targeting the IKKß/NF-κB/A20 Pathway After Spinal Cord Injury.

BACKGROUND/AIMS: miR-136-5p participates in recovery after spinal cord injury (SCI) via an unknown mechanism. We investigated the mechanism underlying the involvement of miR-136-5p in the inflammatory response in a rat model of SCI. METHODS: Sprague-Dawley rat astrocytes were cultured in vitro to construct a reporter plasmid. Luciferase assays were used to detect the ability of miR-136-5p to target the IKKß and A20 genes. Next, recombinant lentiviral vectors were constructed, which either overexpressed miR-136-5p or inhibited its expression. The influence of miR-136-5p overexpression and miR-136-5p silencing on inflammation was observed in vivo in an SCI rat model. The expression of IL-1ß, IL-6, TNF-α, IFN-α, and related proteins (A20, IKKß, and NF-κB) was detected. RESULTS: In vitro studies showed that luciferase activity was significantly activated in the presence of the 3' untranslated region (UTR) region of the IKKß gene after stimulation of cells with miR-136-5p. However, luciferase activity was significantly inhibited in the presence of the 3'UTR region of the A20 gene. Thus, miR-136-5p may act directly on the 3'UTR regions of the IKKß and A20 genes to regulate their expression. miR-136-5p overexpression promoted the production of related cytokines and NF-κB in SCI rats and inhibited the expression of A20 protein. CONCLUSION: Overexpression of miR-136-5p promotes the generation of IL-1ß, IL-6, TNF-α, IFN-α, IKKß, and NF-κB in SCI rats but inhibits the expression of A20. Under these conditions, inflammatory cell infiltration into the rat spinal cord increases and injury is significantly aggravated. Silencing of miR-136-5p significantly reduces the protein expression results described after miR-136-5p overexpression and ameliorates the inflammatory cell infiltration and damage to the spinal cord. Therefore, miR-136-5p might be a new target for the treatment of SCI.