Ultrasound-guided Percutaneous Laser Disc Decompression (PLDD) with Fluoroscopic Validation for the Treatment of Cervical Disc Herniation: Technical Note.

OBJECTIVE: Percutaneous laser disc decompression (PLDD) has been regarded as an effective alternative for the treatment of cervical soft disc herniations. Repeated X-Ray scanning is essential when performing this technique. DESIGN: Technical note. METHODS: We present a new method for the treatment of cervical disc herniation using ultrasound to guide the needle entry to the cervical disc, to avoid excess of radiation exposure during the surgical procedure. We evaluated the efficacy of this cervical approach. We retrospectively reviewed the clinical data of 14 cases who underwent a PLDD under ultrasound guidance for the treatment of contained cervical disc herniation using a 1,470 Nm diode laser. The lower cervical discs (C5-C6 and C6-C7) were the most affected sites, accounting for 78.6% of surgical discs. A significant NRS reduction between baseline and 1 month (P = .0002) and between baseline and 12 months (P = .0007) was observed. CONCLUSIONS: Our results support the conclusion that ultrasound guided PLDD with fluoroscopic validation is a minimally invasive technique for patients affected by herniated cervical discs, but proper choice of patients is critical. This approach should not be performed except after adequate training under close supervision of surgeons experienced in this procedure and in interventional US.

Impact shock origin of diamonds in ureilite meteorites.

The origin of diamonds in ureilite meteorites is a timely topic in planetary geology as recent studies have proposed their formation at static pressures >20 GPa in a large planetary body, like diamonds formed deep within Earth's mantle. We investigated fragments of three diamond-bearing ureilites (two from the Almahata Sitta polymict ureilite and one from the NWA 7983 main group ureilite). In NWA 7983 we found an intimate association of large monocrystalline diamonds (up to at least 100 µm), nanodiamonds, nanographite, and nanometric grains of metallic iron, cohenite, troilite, and likely schreibersite. The diamonds show a striking texture pseudomorphing inferred original graphite laths. The silicates in NWA 7983 record a high degree of shock metamorphism. The coexistence of large monocrystalline diamonds and nanodiamonds in a highly shocked ureilite can be explained by catalyzed transformation from graphite during an impact shock event characterized by peak pressures possibly as low as 15 GPa for relatively long duration (on the order of 4 to 5 s). The formation of "large" (as opposed to nano) diamond crystals could have been enhanced by the catalytic effect of metallic Fe-Ni-C liquid coexisting with graphite during this shock event. We found no evidence that formation of micrometer(s)-sized diamonds or associated Fe-S-P phases in ureilites require high static pressures and long growth times, which makes it unlikely that any of the diamonds in ureilites formed in bodies as large as Mars or Mercury.

Evaluation of Lumbar Adhesiolysis Using a Radiofrequency Catheter During Epiduroscopy in the Treatment of Failed Back Surgery Syndrome (FBSS).

Failed back surgery syndrome (FBSS) is a complication of spinal surgery that results in severe and disabling back/leg pain. Epiduroscopy is a percutaneous minimally invasive surgical technique used in the treatment of lumbar radicular pain that enables both direct visualization of epidural adhesions in patients with FBSS and the mechanical release of fibrotic scars in the epidural space. Although the use of a balloon catheter during epiduroscopy can usually remove adhesions between the dura and the vertebrae, in the thickest areas of fibrosis, the use of a catheter with a molecular quantum resonance radiofrequency generator may resect hard epidural fibrotic obstructions. The aim of this study was to evaluate the efficacy and safety of this radiofrequency catheter in the treatment of severe epidural fibrotic scars. Ninety-three patients with FBSS were enrolled in this study. In 49 cases, a thick area of fibrosis was visualized during epiduroscopy and the use of a balloon catheter could not remove the fibrotic scars. In all of these cases, we used a molecular quantum resonance radiofrequency catheter to remove dense fibrotic areas. Intraoperatively during epiduroscopy, we could directly visualize lysis of the fibrotic scars. Immediately after the procedure and at 1-month and 6-month follow-up, the patients reported significant pain reduction. Pain reduction and patient satisfaction were also reported at 12 months in all but 5 cases. This study found a clinically relevant reduction of pain at 1 and 6 months after epiduroscopy in patients with FBSS. The use of a radiofrequency catheter is safe and effective in resection of hard and thick epidural scars.

Autoimmune Heart Disease: A Comprehensive Summary for Forensic Practice.

Autoimmune heart disease is a non-random condition characterised by immune system-mediated aggression against cardiac tissue. Cardiac changes often exhibit nonspecific features and, if unrecognised, can result in fatal outcomes even among seemingly healthy young individuals. In the absence of reliable medical history, the primary challenge lies in differentiating between the various cardiopathies. Numerous immunohistochemical and genetic studies have endeavoured to characterise distinct types of cardiopathies, facilitating their differentiation during autopsy examinations. However, the presence of a standardised protocol that forensic pathologists can employ to guide their investigations would be beneficial. Hence, this summary aims to present the spectrum of autoimmune cardiopathies, including emerging insights such as SARS-CoV-2-induced cardiopathies, and proposes the utilisation of practical tools, such as blood markers, to aid forensic pathologists in their routine practice.

Factors Predicting Successful Outcome for Ozone Chemonucleolysis in Lumbar Disk Herniation.

OBJECTIVES: The aim of this study was to retrospectively investigate factors predicting a successful outcome after ozone chemonucleolysis (OCN) in patients with radicular pain and poor response to conservative treatments. METHODS: Univariable and multivariable logistic regression analysis was used to identify the predictors of good outcome after OCN. Good outcome was defined as 33% Oswestry Disability Index (ODI) reduction (model 1) or 13-point ODI improvement (model 2) at 1 month after OCN. RESULTS: Two hundred seventy-three patients were analyzed. A significant pain reduction (pre-operative Numerical Rating Scale [NRS] 6.7 ± 1.5, postoperative NRS 2.6 ± 2.2, P < 0.0001) and ODI improvement (pre-operative ODI 39 ± 13.7, postoperative ODI 21.4 ± 13.8, P < 0.0001) was obtained 1 month after OCN. Pain duration (< 1 year), type of disk herniation based on Michigan State University classification (MSU), stages of disk degeneration revealed by discogram and absence of foraminal stenosis (bony or ligament flavum hypertrophy) appeared as predictors of successful outcome. Age, gender, previous spine surgery, level site of disk herniation, presence of uncontained lumbar disk herniation, and vertebral Modic changes were not statistically associated with the outcome. Both the models showed a good accuracy (model 1, area under the curve [AUC] = 0.84 ± 0.027, 95% confidence interval [CI] = 0.79 to 0.89; model 2, AUC = 0.86 ± 0.024, 95% CI = 0.81 to 0.91). CONCLUSIONS: OCN is an effective treatment for radicular pain due to disk herniation. Pain duration (< 1 year), MSU disk herniation type (1A, 1B, 1C, 2A, and 2B), disk degeneration grade 2, and absence of foraminal stenosis are all associated with the successful outcome and should be carefully evaluated before OCN.

Surgical Management of Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma. Experience in 25 Patients.

PURPOSE: To delineate the clinicopathologic features and biologic behavior of the diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) and to report its outcome. METHODS: The clinical records of 25 patients who had surgery for DSV-PTC from 2004 to 2017 were retrospectively analyzed. Comparisons were made to similar studies in the literature reporting ≥8 cases and a cohort of classical PTC. RESULTS: There were 20 females and 5 males with an average age of 23 years (range 10-39 years). Bilateral disease occurred in 80% of cases. The mean size of the dominant mass was 4.2 ± 1.92 cm. In 92% of cases, therapeutic neck dissection was performed. Male sex significantly correlated with a higher yield of positive lymphadenopathy (p = 0.045). 62% of patients had recurrent disease. Recurrence significantly correlated with male sex, the number of metastatic lymph nodes (cutoff: 22 lymph nodes), and multifocality (p = 0.044, p ˂ 0.008, p ˂ 0.003, respectively). However, it did not correlate with the age at presentation. No disease-specific mortality occurred after an average follow-up of 77 months (range 12-168 months). The two comparisons made demonstrated a statistically significant greater tendency of the current series of DSV-PTC toward more aggressive clinicopathologic features and biologic behavior. No differences in overall survival were observed. CONCLUSION: The DSV-PTC should be considered a high-risk PTC that mandates an aggressive therapeutic strategy with the intent of optimizing disease-free survival.

Melanoma in children, adolescents and young adults: anatomo-clinical features and prognostic study on 426 cases.

PURPOSE: This study was conducted to determine the difference in anatomo-pathological and prognostic features of cutaneous melanoma in children, adolescents and young adults. METHODS: This is a retrospective review on 383 young patients ≤ 39 years of age with cutaneous melanoma, in a period from 2006 to 2016 in Area Vasta Nord Ovest, Tuscany, Italy. We subdivided patients in three groups (children ≤ 14 years, adolescents 15-21 years, young adults 22-39 years). We correlated all the anatomo-pathological parameters with age groups. RESULTS: We identified a total of 426 cases of cutaneous melanoma on an overall total of 383 patients. Mean age at diagnosis for all the patients ≤ 39 years of age was 31.2 years: in group A was 11.2 years, in group B 19.2 years and in group C 32.5 years. Incidence, in the subjects between 0 and 14 years, is 14 cases per million inhabitants, between 15 and 21 years of 145, and between 22 and 39 years of 394. Global incidence was 1.6 case per million for group A, 8.9 cases per million for group B, 105 cases per million for group C. No statistically significative correlation could be described for clinical parameters and age groups. CONCLUSIONS: Incidence of melanoma in our casuistry results as the highest in the world. These data open new study for this kind of cancer.

Comparison of Tonic vs. Burst Spinal Cord Stimulation During Trial Period.

BACKGROUND: Spinal cord stimulation (SCS) is a well-known treatment in patients with failed back surgery syndrome (FBSS). Burst stimulation is a recently developed stimulation modality that seems to be superior to tonic stimulation. METHODS: This observational multicenter study compared tonic and burst stimulation during a trial period in patients with FBSS or radiculopathy. All the patients enrolled underwent two weeks of tonic stimulation followed by another two weeks of BurstDR stimulation, without randomization. The primary outcome was the reduction of pain in the legs and back. Health-related quality of life (EQ-5D) and the pain catastrophizing scale (PCS) were assessed before and after the trial. Patients were reevaluated after 12 months. RESULTS: We recruited 23 patients, 57% of whom had FBSS and 43% had radiculopathies. Five patients failed both the tonic and burst stimulation trials. While tonic stimulation reduced leg pain (p < 0.05), the burst mode added an extra pain reduction (ΔNRS 1.2 ± 1.5) (p < 0.01). No significant reduction in back pain was found (p 0.29). Pain on movement was reduced only by BurstDR (p < 0.01). Both stimulation modalities increased EQ-5D and reduced PCS from the baseline (p < 0.0001). At the end of the SCS trial phase, 26% patients chose tonic SCS, while 74% preferred burst. On 12-month follow-up examination, the benefits recorded at the end of the trial were maintained. CONCLUSIONS: Burst stimulation confers a greater reduction in leg pain intensity at rest and on movement. Reducing axial pain is still a challenge. Further studies are needed in order to provide each patient with the most appropriate stimulation paradigm.

Serum soluble urokinase-type plasminogen activator receptor as a serum marker of inflammatory response that leads to tissue damage and surgical complication.

Unrestrained activation of the proteolytic systems in anastomotic tissue during repair has been implicated in the pathogenesis of anastomotic leakage. We hypothesized that this mechanism may promote an up-regulation of the urokinase-type plasminogen activator system and a spillover of soluble urokinase-type plasminogen activator receptor (suPAR) into blood. In this retrospective analysis patients with anastomotic leakage were compared with a group of matched uncomplicated patients. Anastomotic leakage complicated patients had significantly higher suPAR (p = 0.04) levels until day 3 after surgery. The area under the receiver-operating characteristic (ROC) for suPAR was higher than that CRP (0.874 vs. 0.836). Their analysis suggests the possible use of suPAR as serum marker to characterize the persistent inflammatory response that lead to tissue damage and surgical complication.

Crystal structure and microstructural changes of molybdenum nitrides traced during catalytic reaction by in situ X-ray diffraction studies.

X-ray diffraction was used to study changes in the crystal structure and microstructure of molybdenum nitrides during ammonia decomposition. In addition, electron microscopy was employed to analyse morphological changes of the nitrides caused by the catalytic reaction. Molybdenum nitride catalysts (MoxNy) were prepared via high temperature ammonolysis of molybdenum oxide (MoO3) at 650 °C and 800 °C. The materials are nanocrystalline and highly porous, the samples produced at 650 °C still contain the partly reduced precursor (MoO2). In situ X-ray diffraction studies performed on a laboratory instrument equipped with a catalysis reaction chamber reveal significant compositional and structural changes taking place during the reaction. Ball milling, known to enhance the activity of catalysts, has a deleterious effect on the molybdenum nitride specimens: it gives an initial boost due to the reduction of size and increase in dislocation content, but it also favours the formation of the less active hexagonal MoN.

Sudden cardiac death during scuba diving: a case report of a patient with unknown hypertrophic cardiomyopathy.

Background: Scuba diving is a recreational activity usually considered at low impact on cardiovascular system. However, when diving, increased ambient pressure exerts several effects on the cardiovascular and pulmonary systems, mainly due to redistribution of peripheral blood into the central circulation. This phenomenon, also known as blood shift, may produce a significant overload on a non-healthy heart. Case summary: We present the case of a female patient who experienced sudden cardiac death during scuba diving: post-mortem cardiac magnetic resonance and autopsy revealed that the patient was affected by previously unknown hypertrophic cardiomyopathy. Discussion: Diving exposes the body to significant physiological changes that may overstress a diseased heart. This case suggests the need for some cardiovascular exams, such as an echocardiogram or, at least, an electrocardiogram, for screening cardiovascular abnormalities in subjects who wish to practice scuba diving.

Stand-Alone Percutaneous Pedicle Screw Lumbar Fixation to Indirectly Decompress the Neural Elements in Spinal Stenosis: A Radiographic Assessment Case Series.

BACKGROUND: The ideal surgical treatment of lumbar canal stenosis remains controversial. Although decompressive open surgery has been widely used with good clinical outcome, minimally invasive indirect decompression techniques have been developed to avoid the complications associated with open approaches. The purpose of this study was to evaluate the radiologic outcome and safety of the indirect decompression achieved with stand-alone percutaneous pedicle screw fixation in the surgical treatment of lumbar degenerative pathologies. METHODS: Twenty-eight patients presenting with spinal degenerative diseases including concomitant central and/or lateral stenosis were treated with stand-alone percutaneous pedicle screw fixation. Radiographic measurements were made on axial and sagittal magnetic resonance (MR) images, performed before surgery and after a mean follow-up period of 25.2 months. Measurements included spinal canal and foraminal areas, and anteroposterior canal diameter. RESULTS: Percutaneous screw fixation was performed in 35 spinal levels. Measurements on the follow-up MR images showed statistically significant increase in the cross-sectional area of the spinal canal and the neural foramen, from a mean of 88.22 and 61.05 mm2 preoperatively to 141.52 and 92.18 mm2 at final follow-up, respectively. The sagittal central canal diameter increased from a mean of 4.9 to 9.1 mm at final follow-up. Visual analog scale (VAS) pain score and Oswestry Disability Index (ODI) both improved significantly after surgery (p < 0.0001). CONCLUSION: Stand-alone percutaneous pedicle screw fixation is a safe and effective technique for indirect decompression of the spinal canal and neural foramina in lumbar degenerative diseases. This minimally invasive technique may provide the necessary decompression in cases of common degenerative lumbar disorders with ligamentous stenosis.

Delphi-Based Expert Consensus Statements for the Management of Percutaneous Radiofrequency Neurotomy in the Treatment of Lumbar Facet Joint Syndrome.

INTRODUCTION: A modified Delphi strategy was implemented for obtaining recommendations that could be useful in the management of percutaneous radiofrequency treatment of lumbar facet joint syndrome, as the literature on the argument was poor in quality. METHODS: An Italian research team conducted a comprehensive literature search, defined the investigation topics (diagnosis, treatment, and outcome evaluation), and developed an explorative semi-structured questionnaire. They also selected the members of the panel. After an online meeting with the participants, the board developed a structured questionnaire of 15 closed statements (round 1). A five-point Likert scale was used and the cut-off for consensus was established at a minimum of 70% of the number of respondents (level of agreement ≥ 4, agree or strongly agree). The statements without consensus were rephrased (round 2). RESULTS: Forty-one clinicians were included in the panel and responded in both rounds. After the first round, consensus (≥ 70%) was obtained in 9 out of 15 statements. In the second round, only one out of six statements reached the threshold. The lack of consensus was observed for statements concerning the use of imaging for a diagnosis [54%, median 4, interquartile range (IQR) 3-5], number of diagnostic blocks (37%, median 4, IQR 2-4), bilateral denervation (59%, median 4, IQR 2-4), technique and number of lesions (66%, median 4, IQR 3-5), and strategy after denervation failure (68%, median 4, IQR 3-4). CONCLUSION: Results of the Delphi investigations suggest that there is a need to define standardized protocols to address this clinical problem. This step is essential for designing high-quality studies and filling current gaps in scientific evidence.

Corrosion Inhibition of Carbon Steel in a Sour (H2S) Environment by an Acryloyl-Based Polymer.

Corrosion poses safety and operational challenges in the oil and gas field, particularly in a sour environment. Corrosion inhibitors (CIs) are thus employed to protect the integrity of industrial assets. However, CIs have the potential to dramatically impair the effectiveness of other co-additives, such as kinetic hydrate inhibitors (KHIs). Here, we propose an acryloyl-based copolymer, previously used as a KHI, as an effective CI. The copolymer formulation provided a corrosion inhibition efficiency of up to 90% in a gas production environment, implying that it can reduce or even eliminate the need for an additional dedicated CI in the system. It also demonstrated a corrosion inhibition efficiency of up to 60% under field-simulated conditions for a wet sour crude processing environment. Molecular modeling suggests that the enhanced corrosion protection is imparted by the favorable interaction of the heteroatoms of the copolymer with the steel surface, potentially displacing adhered water molecules. All in all, we show that an acryloyl-based copolymer with dual functionalities can potentially overcome issues caused by incompatibilities in a sour environment, resulting in significant cost savings and operational ease.

Combination Drug Therapy for the Management of Chronic Neuropathic Pain.

Chronic neuropathic pain (NP) is an increasingly prevalent disease and leading cause of disability which is challenging to treat. Several distinct classes of drugs are currently used for the treatment of chronic NP, but each drug targets only narrow components of the underlying pathophysiological mechanisms, bears limited efficacy, and comes with dose-limiting side effects. Multimodal therapies have been increasingly proposed as potential therapeutic approaches to target the multiple mechanisms underlying nociceptive transmission and modulation. However, while preclinical studies with combination therapies showed promise to improve efficacy over monotherapy, clinical trial data on their efficacy in specific populations are lacking and increased risk for adverse effects should be carefully considered. Drug-drug co-crystallization has emerged as an innovative pharmacological approach which can combine two or more different active pharmaceutical ingredients in a single crystal, optimizing pharmacokinetic and physicochemical characteristics of the native molecules, thus potentially capitalizing on the synergistic efficacy between classes of drugs while simplifying adherence and minimizing the risk of side effects by reducing the doses. In this work, we review the current pharmacological options for the treatment of chronic NP, focusing on combination therapies and their ongoing developing programs and highlighting the potential of co-crystals as novel approaches to chronic NP management.

Strain in atomistic models of nanocrystalline clusters.

Strain, as an easy and clearly defined concept in continuum mechanics, has no direct counterpart in atomistic models. Existing methods, relying on the concept of atomic coordination number, do not provide a complete description of volumetric and deviatoric strains across metallic nanocrystalline microstructures. To overcome those limitations a new method is proposed: the Voronoi Cell deformation (VCD) fully accounts for the local geometry and provides a description of the strain field independent of the atomic coordination. As a typical case of study, a large atomic cluster of 200 Al grains (ca 2 million atoms) and overall size of 33 cubic nanometres was considered.

The modified NUTRIC score (mNUTRIC) is associated with increased 28-day mortality in critically ill COVID-19 patients: Internal validation of a prediction model.

BACKGROUND: High prevalence of malnutrition was found in critically ill COVID-19 patients. The modified Nutrition Risk in the Critically ill (mNUTRIC) score is frequently used for nutritional risk assessment in intensive care unit (ICU) COVID-19 patients. The aim of this study was to investigate the role of mNUTRIC score to predict 28-day mortality in critically ill COVID-19 patients admitted to ICU. METHODS: A cohort of consecutive COVID-19 critically ill patients admitted to ICU was retrospectively evaluated and the nutritional risk was assessed with the use of mNUTRIC score. A multivariable Cox regression model to predict 28-day mortality was therefore developed including the mNUTRIC as a covariate. Internal validation was performed using the bootstrap resampling technique to reduce possible bias in the estimated risks. The performance of the prediction model was assessed via calibration and discrimination. RESULTS: A total of 98 critically ill COVID-19 patients with a median age of 66 years (56-73 IQR), 81 (82.7%) males were included in this study. A high nutritional risk (mNUTRIC ≥5 points) was observed in 41.8% of our critically ill COVID-19 patients while a low nutritional risk (mNUTRIC <5 points) was observed in 58.2%. Forty-five patients (45.9%) died within 28 days after ICU admission. In multivariable model after internal validation, mNUTRIC ≥5 (optimism adjusted HR 2.38, 95% CI 1.08-5.25, p = 0.02) and high-sensitivity C-reactive protein values (CRP) (optimism adjusted HR 1.02, 95% CI 1.01-1.07, p = 0.005) were independent predictors of 28-day mortality. CONCLUSIONS: A high prevalence of malnutrition as revealed by mNUTRIC was found in our critically ill COVID-19 patients once admitted in ICU. After adjustment for covariables, mNUTRIC ≥5 and CRP levels were independently associated with 28-day mortality in critically ill COVID-19 patients. The final model revealed good discrimination and calibration. Nutritional risk assessment is essential for the management of critically ill COVID-19 patients as well as for outcome prediction.

Radiation Exposure during Fluoroscopy-Guided Ozone Chemonucleolysis for Lumbar Disc Herniation.

Introduction: Radiation exposure is a frequent drawback of spinal surgery, even if X-ray guidance plays a pivotal role in improving the accuracy and safety of spinal procedures. Consequently, radiation protection is essential to reduce potential negative biological effects. The aim of this study was to evaluate patients' radiation exposure, the radiation dose emission during fluoroscopy-guided ozone chemonucleolysis (OCN), and the potential role of patient characteristics. Methods: The radiation dose emission reports were retrospectively evaluated in patients who underwent single-level OCN for lumbar disc herniation. A generalized linear model (GLM) with a gamma distribution and log link function was used to assess the association between radiation emission and patients' characteristics such as age, sex, BMI, level of disc herniation, disc height, and site of disc herniation. Results: Two hundred and forty OCN cases were analyzed. A safe and low level of radiation exposure was registered during OCN. The median fluoroscopy time for OCN was 26.3 (19.4−35.9) seconds, the median radiation emission dose was 19.3 (13.2−27.3) mGy, and he median kerma area product (KAP) was 0.46 (0.33−0.68) mGy ⋅ m2. The resulting KAP values were highly dependent on patient variables. In particular, sex, obesity, and residual disc height < 50% significantly increased the measured KAP, while levels of disc herniations other than L5-S1 reduced the KAP values. Conclusions: The radiation exposure during OCN is low and quite similar to a simple discography. However, patient characteristics are significantly related to radiation exposure and should be carefully evaluated before planning OCN.

Human umbilical cord blood mesenchymal stem cells protect mice brain after trauma.

OBJECTIVE: To investigate whether human umbilical cord blood mesenchymal stem cells, a novel source of progenitors with multilineage potential: 1) decrease traumatic brain injury sequelae and restore brain function; 2) are able to survive and home to the lesioned region; and 3) induce relevant changes in the environment in which they are infused. DESIGN: Prospective experimental study. SETTING: Research laboratory. SUBJECTS: Male C57Bl/6 mice. INTERVENTIONS: Mice were subjected to controlled cortical impact/sham brain injury. At 24 hrs postinjury, human umbilical cord blood mesenchymal stem cells (150,000/5 µL) or phosphate-buffered saline (control group) were infused intracerebroventricularly contralateral to the injured side. Immunosuppression was achieved by cyclosporine A (10 mg/kg intraperitoneally). MEASUREMENTS AND MAIN RESULTS: After controlled cortical impact, human umbilical cord blood mesenchymal stem cell transplantation induced an early and long-lasting improvement in sensorimotor functions assessed by neuroscore and beam walk tests. One month postinjury, human umbilical cord blood mesenchymal stem cell mice showed attenuated learning dysfunction at the Morris water maze and reduced contusion volume compared with controls. Hoechst positive human umbilical cord blood mesenchymal stem cells homed to lesioned tissue as early as 1 wk after injury in 67% of mice and survived in the injured brain up to 5 wks. By 3 days postinjury, cell infusion significantly increased brain-derived neurotrophic factor concentration into the lesioned tissue, restoring its expression close to the levels observed in sham operated mice. By 7 days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a nonphagocytic activation of microglia/macrophages as shown by a selective rise (260%) in CD11b staining (a marker of microglia/macrophage activation/recruitment) associated with a decrease (58%) in CD68 (a marker of active phagocytosis). Thirty-five days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a decrease of glial fibrillary acidic protein positivity in the scar region compared with control mice. CONCLUSIONS: These findings indicate that human umbilical cord blood mesenchymal stem cells stimulate the injured brain and evoke trophic events, microglia/macrophage phenotypical switch, and glial scar inhibitory effects that remodel the brain and lead to significant improvement of neurologic outcome.