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1.
J Anesth ; 38(1): 35-43, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37898990

RESUMEN

PURPOSE: There are few reports regarding the association between the neutrophil-lymphocyte ratio (NLR), uric acid, and the development of postoperative delirium (POD) in patients who are undergoing spine surgeries. We investigated the associations between the NLR, uric acid as a natural antioxidant, and POD in elderly patients undergoing degenerative spine surgery. PATIENTS AND METHODS: This was a single-center, observational, and retrospective study conducted in Japan. We enrolled 410 patients who underwent degenerative spine surgery. POD was diagnosed after the surgeries by psychiatrists, based on the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). We performed a multivariable logistic regression analysis to clarify whether the NLR and uric acid values were associated with the development of POD in the patients. RESULTS: 129 of the 410 patients were excluded from the analysis. Of the 281 patients (137 females, 144 males), 32 patients (11.4%) were diagnosed with POD. The multivariable logistic regression analysis revealed that the preoperative uric acid level (adjusted odds ratio [aOR]: 0.67, 95% confidence interval [CI]: 0.49-0.90, p = 0.008) and age (aOR: 1.09, 95% CI: 1.02-1.16, p = 0.008) were significantly associated with POD. The preoperative NLR (aOR: 0.82, 95% CI: 0.60-1.13, p = 0.227) and antihyperuricemic medication (aOR: 0.97, 95% CI: 0.24-3.82, p = 0.959) were not significantly associated with POD. CONCLUSION: Our results demonstrated that in elderly patients undergoing degenerative spine surgery, the preoperative NLR was not significantly associated with POD, but a lower preoperative uric acid value was an independent risk factor for developing POD. Uric acid could have a neuroprotective impact on POD in patients with degenerative spine diseases.


Asunto(s)
Delirio , Delirio del Despertar , Masculino , Femenino , Humanos , Anciano , Ácido Úrico , Estudios Retrospectivos , Neutrófilos , Complicaciones Posoperatorias , Factores de Riesgo , Linfocitos
2.
Eur Spine J ; 32(10): 3352-3359, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37326838

RESUMEN

PURPOSE: This study aimed to evaluate the association between cervical atherosclerosis on Doppler ultrasonography and postoperative delirium (POD) in patients undergoing spinal surgery. METHODS: In this retrospective observational study using prospectively collected data, 295 consecutive patients aged > 50 years underwent spine surgery at a single institution between March 2015 and February 2021. Cervical atherosclerosis was defined as the intima-media thickness (IMT) of the common carotid artery (CCA) being ≥ 1.1 mm on pulsed-wave Doppler ultrasonography. Univariate and multivariate logistic regression analyses were performed with the prevalence of postoperative delirium as a dependent variable. Age, sex, body mass index, medical history, American Society of Anesthesiologists Physical Status (ASA-PS), CHADS2 score (an assessment score for stroke), instrumentation, duration of surgery, blood loss, and cervical arteriosclerosis were the independent variables. RESULTS: Twenty-seven patients of 295 (9.2%) developed delirium postoperatively. Forty-one (13.9%) of the 295 patients had cervical atherosclerosis. Their univariate analyses showed that age (P = 0.001), hypertension (P = 0.016), cancer (P = 0.046), antiplatelet agent use (P < 0.001), ASA-PS ≥ 3 (P < 0.001), CHADS2 score (P < 0.001), cervical atherosclerosis (P = 0.008), and right CCA-IMT (P = 0.007) were significantly associated with POD. However, multivariate logistic regression analyses showed older age (odds ratio [OR], 1.109; 95% confidence interval [CI] 1.035-1.188; P = 0.03) and antiplatelet agent use (OR, 3.472; 95% CI 1.221-9.870; P = 0.020) to be significantly associated with POD. CONCLUSIONS: There was a significant association between POD and the prevalence of cervical atherosclerosis using the univariate logistic regression analysis. Furthermore, multivariate logistic regression analyses showed that older age and antiplatelet agent use were independently associated with POD.


Asunto(s)
Aterosclerosis , Delirio , Delirio del Despertar , Humanos , Estudios Retrospectivos , Factores de Riesgo , Delirio/epidemiología , Grosor Intima-Media Carotídeo , Inhibidores de Agregación Plaquetaria , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiología , Ultrasonografía Doppler
4.
Medicine (Baltimore) ; 102(49): e36194, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38065880

RESUMEN

This study aimed to clarify the association between swallowing disorder and prevertebral hyperintensity on magnetic resonance imaging (MRI) in patients with cervical spinal cord injury (CSCI) without a major fracture. This retrospective observational study included 30 patients who were diagnosed with acute CSCI without a major fracture (mean age: 69.3 years, 27 men). Swallowing disorder was defined as tube-dependent nutrition because of obvious aspiration 28 days after injury. The high-intensity area (HIA) and anteroposterior width (HIW) of the prevertebral space at C1-7 levels were measured using MRI short-TI inversion recovery midsagittal images. Receiver operating characteristic curve analysis was used to determine the optimal cutoff values of the HIA for predicting swallowing disorder. The incidence of swallowing disorder after CSCI was 16.7%. The HIA was significantly higher in the swallowing disorder group (median, 409.0 mm2) than in the non- swallowing disorder group (median, 159.1 mm2) (P = .04). There was no significant difference in HIW between the two groups. The optimal cutoff point of the HIA was measured at 203.2 mm2 with 80.0% and 20.0% sensitivity and specificity, respectively, with an area under the curve of 0.848 (95% confidence interval, 0.657-1.000, P = .01). The prevertebral hyperintensity area on MRI for swallowing disorder in patients after cervical cord injury without skeletal injury is associated with swallowing disorder. The optimal cutoff point of the area was determined to be 203.2 mm2.


Asunto(s)
Médula Cervical , Trastornos de Deglución , Fracturas Óseas , Traumatismos del Cuello , Traumatismos de los Tejidos Blandos , Traumatismos de la Médula Espinal , Anciano , Humanos , Masculino , Médula Cervical/lesiones , Vértebras Cervicales/patología , Trastornos de Deglución/etiología , Trastornos de Deglución/complicaciones , Fracturas Óseas/complicaciones , Imagen por Resonancia Magnética/métodos , Traumatismos del Cuello/complicaciones , Estudios Retrospectivos , Traumatismos de los Tejidos Blandos/complicaciones , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/diagnóstico por imagen , Femenino
5.
Medicine (Baltimore) ; 102(39): e35369, 2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37773811

RESUMEN

The Injury Severity Score (ISS) is widely used to evaluate patients with multiple injuries. This study investigated the association between ISS and clinical outcomes of patients with spinal cord injury (SCI) in an aging Japanese population. This retrospective cohort study investigated patients admitted to a Japanese university hospital. In the study, 89 patients with traumatic SCI were included. Traumatic SCI was categorized as monotrauma or polytrauma, and the ISS was used to evaluate trauma severity. Spearman's correlation coefficient was used to estimate the correlation between ISS and the American Spinal Injury Association (ASIA) motor score, Barthel Index (activities of daily living assessment), and the European Quality of Life (QOL) scale (EQ5d) as an assessment of QOL at admission or the last follow-up with the adjustment for age, sex, and body mass index. Return to home and work were analyzed using the chi-squared test after the ISS was divided into three groups (<14, 14-19, and 20). The mean ISS was significantly higher for polytrauma than monotrauma. Significant negative correlations between the ISS and ASIA motor scores at the first visit (P < .001, r = -0.37) and the last follow-up (adjusted, P = .007, r = -0.30) were observed. The Barthel Index was also negatively correlated with ISS at the first visit (P = .04, r = -0.21) and at the last follow-up period (P < .001, r = -0.35). Moreover, ISS was significantly negatively correlated with EQ5d score at the last follow-up (P = .01, r = -0.28). The chi-squared test demonstrated that patients with an ISS of < 14 returned home (P = .03), while those with an ISS of < 19 returned to work (P = .02). ISS is associated with paralysis, activities of daily living, QOL, and lifestyle in patients with SCI and is an important initial injury assessment method.


Asunto(s)
Traumatismo Múltiple , Traumatismos de la Médula Espinal , Traumatismos Vertebrales , Humanos , Puntaje de Gravedad del Traumatismo , Calidad de Vida , Estudios Retrospectivos , Actividades Cotidianas , Pueblos del Este de Asia , Envejecimiento
6.
Spine Deform ; 11(2): 481-486, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36380109

RESUMEN

PURPOSE: To determine the frequencies of various diseases associated with all types of early-onset scoliosis, both idiopathic and nonidiopathic. METHODS: Retrospective collection of patients within a 21-year interval. Children under 10 years old presenting with scoliosis were included. Medical records were used to collect: identifier, date of birth, sex, diagnosis, follow-up, curve pattern, comorbidities, initial and final cobb angle. Different patient variables were tabulated with associated comorbidities for comparison. RESULTS: The cohort contained 469 patients, with 227(48.4%) males and 242(51.6%) females. Total comorbidities equaled 1051, where 190 were unique. Only 124(26.4%) patients had an isolated diagnosis of early-onset scoliosis, 79(16.8%) had a single comorbidity, and 266(56.7%) had multiple comorbidities. "Global developmental delay" was most commonly observed, 198(42.2%) times. The central nervous system was involved more often than other organ systems, seen in 394(54.4%) instances. Males had more comorbidities than females. Idiopathic patients had the least number of comorbidities, while neuromuscular patients had the most. Idiopathic types had more musculoskeletal conditions, while congenital types had more cardiovascular diseases. Curve sides did not affect distributions. Cases which progressed had more comorbidities, especially in the respiratory, digestive, and cardiovascular systems. Diseases that could affect either extremity or side, were more likely to be bilateral. CONCLUSIONS: Early-onset scoliosis patients may present with complex comorbidities in multiple organ systems. The most commonly observed disease entities were: global developmental delay, developmental dysplasia of the hip, and epilepsy. Clinicians should be aware of the common associations, in order to screen for and begin appropriate investigations, referrals, and treatments in affected cases. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Escoliosis , Niño , Masculino , Femenino , Humanos , Escoliosis/epidemiología , Escoliosis/terapia , Estudios Retrospectivos , Comorbilidad , Extremidades , Moldes Quirúrgicos
7.
Spine (Phila Pa 1976) ; 48(1): 67-72, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36007127

RESUMEN

STUDY DESIGN: This was a retrospective multicenter study. OBJECTIVE: To develop a novel progression risk stratification scoring system for early-onset scoliosis. SUMMARY OF BACKGROUND DATA: There is a lack of investigations into variables affecting the risk of curve progression in early-onset scoliosis, which prevents stratification. A novel risk score system is needed to help in progression risk estimation. METHODS: A retrospective analysis was done at three centers, from 1995 to 2020. Scoliosis cases before the age of 10 years, were included. Medical identifier, date of birth, sex, primary diagnosis, curve type, date/modality of treatment, date of follow-up appointments, and Cobb angles, were collected. Five ranks were selected for stratification. Categories with the same ranks were discarded. Point scores started at 0, for the lowest risk, and ended at 4, for highest risk. Iterations of variable combinations were conducted and clinical relevance was determined by evaluating sensitivity, specificity, positive predictive value, and negative predictive value based on score ranges for low and high risk of progression. RESULTS: A total of 476 (230 males, 246 females) early-onset scoliosis patients were collected. The average age at diagnosis was 4.8 years (SD±2.8 yr). The average follow-up duration was 9.3 years (SD±6.9 yr, range: 5 mo-38 yr). Appointments totaled 2911, giving 2182 observations for the analysis. Patient observations numbered: 800 (36.7%) ending in progression, 1265 (58.0%) for nonprogression, 117 (5.4%) for inadequate follow-up, and 368 (16.9%) for rapid progression. The risk scoring system contained four categories: etiology, age, curve magnitude, and curve type. Categorized point combinations totaled 755, giving 1975 iterations. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to be 85.8%, 96.5%, 89.7%, and 95.1%, respectively. CONCLUSION: A novel progression risk score for early-onset scoliosis was derived. The system can reliably differentiate between low and high-risk cases in clinical settings. Further validation in other regions may be important for verifying clinical relevance. LEVEL OF EVIDENCE: Level 3.


Asunto(s)
Escoliosis , Masculino , Femenino , Humanos , Preescolar , Niño , Estudios Retrospectivos , Escoliosis/diagnóstico , Escoliosis/epidemiología , Escoliosis/terapia , Valor Predictivo de las Pruebas , Factores de Riesgo , Progresión de la Enfermedad
8.
J Neurotrauma ; 40(23-24): 2596-2609, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37051701

RESUMEN

Abstract Spinal cord injury (SCI) is a serious neurological disorder, with the consequent disabilities conferred by this disorder typically persisting for life. Multilineage-differentiating stress-enduring (Muse) cells are endogenous stem cells that can be collected from various tissues as well as from mesenchymal stem cells (MSCs); additionally, these Muse cells are currently being used in clinical trials. The anti-inflammatory effect of stem cell transplantation prevents secondary injuries of SCI; however, its effect on Muse cells remains unclear. In this study, we aimed to compare the anti-inflammatory effects of adipose (AD)- and bone marrow (BM)-Muse cells that were isolated from mice (6-week-old C57BL/6J) following intralesional administration during the acute phase of SCI. Flow cytometry was used to isolate Muse cells from AD and BM MSCs. The percentage of Muse cells was 3.9 and 2.7% for AD and BM MSCs, respectively. To examine cell viability, Muse cells were incubated under H2O2-induced oxidative stress conditions. Overall, AD-Muse cells exhibited higher viability than BM-Muse cells (p = 0.032). In enzyme-linked immunosorbent assay analysis, AD-Muse cells displayed greater secretion of brain-derived neurotrophic factor (BDNF; p = 0.008), vascular endothelial growth factor (p = 0.032), and hepatocyte growth factor (p = 0.016). DNA microarray analysis revealed higher expression of Bdnf, neurotrophin-3 (Ntf3), nerve growth factor (Ngf), pleiotrophin (Ptn), and midkine (Mdk) in AD-Muse cells than in BM-Muse cells. To assess their anti-inflammatory effects in vitro, Muse cells and macrophages were co-cultured, and the levels of cytokines (tumor necrosis factor [TNF] α and interleukin [IL] 10) were measured in the medium. Consequently, we found that TNFα levels were lower in AD-Muse cells than in BM-Muse cells (p = 0.009), and IL10 levels were higher in AD-Muse cells than in BM-Muse cells (p = 0.008). Further, we induced moderate injuries via contusion of the spinal cord at the T10 level; Muse cells were transplanted intralesionally 7 days post-SCI. The number of surviving cells, alongside the number of CD86+ (M1 inflammatory effect), and CD206+ (M2 anti-inflammatory effect) macrophages in the spinal cord were measured 7 days post-transplantation. The number of surviving AD-Muse cells was higher than the number of surviving BM-Muse cells (ratio of AD-Muse/BM-Muse = 2.5, p > 0.05). The M1/M2 ratio in the AD-Muse cell-group (0.37) was lower than that in the control (phosphate-buffered saline) group (3.60, p = 0.008). The lesion area in the AD-Muse cell group was smaller than that in the BM-non-Muse (p = 0.049) and control groups (p = 0.012). As AD-Muse cells conferred a higher cell survival and neurotrophic factor secretion ability in vitro, AD-Muse cells demonstrated reduced inflammation after SCI. Overall, intralesional AD-Muse cell therapy is a potential therapeutic candidate that is expected to exhibit anti-inflammatory effects following acute SCI.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Traumatismos de la Médula Espinal , Ratones , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Médula Ósea/metabolismo , Médula Ósea/patología , Factor A de Crecimiento Endotelial Vascular , Alprostadil , Peróxido de Hidrógeno , Ratones Endogámicos C57BL , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/patología , Médula Espinal/metabolismo , Antiinflamatorios
9.
Neurotrauma Rep ; 4(1): 82-96, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36874147

RESUMEN

Neuroinflammation occurs in the acute phase of spinal cord injury (SCI) and inhibits neural regeneration. In mouse models, etizolam (ETZ) is a strong anxiolytic with unclear effects on SCI. This study investigated the effects of short-term administration of ETZ on neuroinflammation and behavior in mice after SCI. We administrated an ETZ (0.5 mg/kg) daily intraperitoneal injection from the day after SCI for 7 days. Mice were randomly divided into three groups (sham group: only laminectomy, saline group, and ETZ group). Inflammatory cytokine concentrations in the injured spinal cord epicenter were measured using an enzyme-linked immunosorbent assay on day 7 after SCI to evaluate spinal cord inflammation in the acute phase. Behavior analysis was performed the day before surgery and on days 7, 14, 28, and 42 after surgery. The behavioral analysis included anxiety-like behavior using the open field test, locomotor function using the Basso Mouse Scale, and sensory function using the mechanical and heat test. Inflammatory cytokine concentrations were significantly lower in the ETZ group than in the saline group in the acute phase after spinal surgery. After SCI, anxiety-like behaviors and sensory functions were comparable between the ETZ and saline groups. ETZ administration reduced neuroinflammation in the spinal cord and improved locomotor function. Gamma-amino butyric acid type A receptor stimulants may be effective therapeutic agents for patients with SCI.

10.
J Orthop Surg Res ; 17(1): 52, 2022 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-35093097

RESUMEN

PURPOSE: Although the use of intraoperative computed tomography (CT)-based navigation systems is unlikely to cause intraoperative contamination more than the use of intraoperative fluoroscopy, the association between intraoperative CT/navigation and surgical site infections (SSIs) remains unclear. We investigated the incidence of SSIs and the association between intraoperative CT/navigation and SSIs for spinal surgeries. METHODS: Of the 512 patients who underwent spinal surgery between April 2016 and December 2020, 304 underwent C-arm intraoperative fluoroscopy and/or Medtronic O-arm intraoperative CT/navigation system. We investigated the incidence of SSIs in patients with four techniques; no intraoperative imaging C-arm only, O-arm only, and both O- and C-arm used. Multivariate logistic analyses were conducted using the prevalence of SSIs as the dependent variable. The independent variables were age, sex, and potential confounders including preoperative Japanese Orthopaedic Association (JOA) score, use of instrumentation, C-arm, and/or O-arm. RESULTS: The incidence of the SSIs in patients with no imaging, C-arm only, O-arm only, and both modalities used was 1.9%, 7.3%, 4.7%, and 8.3%, respectively. There was no significant difference in the incidence of SSIs between the four techniques. Multivariate logistic analyses showed a significant correlation between the prevalence of SSI and JOA scores (odds ratio, 0.878; 95% CI 0.759-0.990) and use of instrumentation (odds ratio, 6.241; 95% CI 1.113-34.985), but not use of O-arm. CONCLUSIONS: The incidence of the SSIs in patients with only O-arm used was 4.7%. Preoperative clinical status and use of instrumentation, but not use of the O-arm, were associated with SSIs after spinal surgeries.


Asunto(s)
Imagenología Tridimensional , Columna Vertebral/cirugía , Cirugía Asistida por Computador , Infección de la Herida Quirúrgica/epidemiología , Tomografía Computarizada por Rayos X/métodos , Anciano , Femenino , Fluoroscopía , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Infección de la Herida Quirúrgica/diagnóstico por imagen , Infección de la Herida Quirúrgica/etiología
11.
Spine J ; 22(9): 1540-1550, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35381360

RESUMEN

BACKGROUND CONTEXT: Despite the many advances in understanding and treating early-onset scoliosis, the incidence and prevalence of this disease in the population remains unknown. Such knowledge is important for guiding clinical practice, directing research and raising awareness. PURPOSE: To identify the incidence and prevalence of early-onset scoliosis, including all categories, within the population. STUDY DESIGN: A regional multicenter retrospective cohort study PATIENT SAMPLE: All patients diagnosed with early-onset scoliosis in the region, who were followed-up between January 2000 and December 2020. OUTCOME MEASURES: Frequency distributions for early-onset scoliosis subtypes, demographics, curve patterns and progression statuses. METHODS: Relevant population data, for children under 10 years old, was extracted from the official government census for the years 2000 to 2020. Identification of cases was carried out by pediatricians at mandatory government funded regular child wellness check-up visits. Outpatient records were reviewed for all included patients, with extraction of the following: Medical identifier, date of birth, date of initial visit, sex, primary diagnosis, length of follow-up, curve pattern, initial cobb angle, and final cobb angle. Incidence and prevalence values were calculated using population figures and case numbers. Kaplan-Meier survival analysis and Log-rank testing was performed on curve progression data. RESULTS: The regional population of children, under the age of 10 years, included a total of 2,295,929 children, 1,170,149 (51.0%) males and 1,125,780 (49.0%) females, between the years 2000 and 2020. Early-onset scoliosis cases followed within the same timeframe, totaled 469 patients, 227 (48.4%) males and 242 (51.6%) females. The annual incidence of early-onset scoliosis was found to be 0.019% (95% CI: 0.015%-0.023%), and the prevalence was 0.077% (95% CI: 0.059%-0.096%). The most common age at first presentation was 6 years old. More females (51.6%) than males (48.4%) were observed, and more left-sided curves (54.2%) than right-sided curves (45.8%) were encountered, with the majority being single thoracic curves (38.2%). Scoliosis curves did not progress in 44.3% of cases, while they progressed in 38% of them. Follow-up was inadequate to determine progression status in 17.7% of cases. Neuromuscular etiologies were the most common, at 40.1%, of which 83.5% had cerebral palsy. CONCLUSIONS: Based on the regional population included in this study, the annual incidence of early-onset scoliosis in children under 10 years old was calculated to be 0.019%, while the prevalence of early-onset scoliosis in children under 10 years old was found to be 0.077%.


Asunto(s)
Escoliosis , Niño , Femenino , Humanos , Incidencia , Masculino , Prevalencia , Estudios Retrospectivos , Escoliosis/epidemiología , Escoliosis/terapia
12.
Cells ; 11(7)2022 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-35406701

RESUMEN

A bone marrow-derived mesenchymal stromal cell (MSC) transplant and a bioengineered nanofiber-hydrogel composite (NHC) have been shown to stimulate nervous tissue repair in the contused spinal cord in rodent models. Here, these two modalities were combined to assess their repair effects in the contused spinal cord in adult rats. Cohorts of contused rats were treated with MSC in NHC (MSC-NHC), MSC in phosphate-buffered saline (MSC-PBS), NHC, or PBS injected into the contusion site at 3 days post-injury. One week after injury, there were significantly fewer CD68+ cells in the contusion with MSC-NHC and NHC, but not MSC-PBS. The reduction in CD86+ cells in the injury site with MSC-NHC was mainly attributed to NHC. One and eight weeks after injury, we found a greater CD206+/CD86+ cell ratio with MSC-NHC or NHC, but not MSC-PBS, indicating a shift from a pro-inflammatory towards an anti-inflammatory milieu in the injury site. Eight weeks after injury, the injury size was significantly reduced with MSC-NHC, NHC, and MSC-PBS. At this time, astrocyte, and axon presence in the injury site was greater with MSC-NHC compared with MSC-PBS. We did not find a significant effect of NHC on MSC transplant survival, and hind limb function was similar across all groups. However, we did find fewer macrophages at 1 week post-injury, more macrophages polarized towards a pro-regenerative phenotype at 1 and 8 weeks after injury, and reduced injury volume, more astrocytes, and more axons at 8 weeks after injury in rats with MSC-NHC and NHC alone compared with MSC-PBS; these findings were especially significant between rats with MSC-NHC and MSC-PBS. The data support further study in the use of an NHC-MSC combination transplant in the contused spinal cord.


Asunto(s)
Contusiones , Células Madre Mesenquimatosas , Nanofibras , Traumatismos de la Médula Espinal , Animales , Hidrogeles , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/terapia
13.
Biomaterials ; 245: 119978, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32217415

RESUMEN

An injury to the spinal cord causes long-lasting loss of nervous tissue because endogenous nervous tissue repair and regeneration at the site of injury is limited. We engineered an injectable nanofiber-hydrogel composite (NHC) with interfacial bonding to provide mechanical strength and porosity and examined its effect on repair and neural tissue regeneration in an adult rat model of spinal cord contusion. At 28 days after treatment with NHC, the width of the contused spinal cord segment was 2-fold larger than in controls. With NHC treatment, tissue in the injury had a 2-fold higher M2/M1 macrophage ratio, 5-fold higher blood vessel density, 2.6-fold higher immature neuron presence, 2.4-fold higher axon density, and a similar glial scar presence compared with controls. Spared nervous tissue volume in the contused segment and hind limb function was similar between groups. Our findings indicated that NHC provided mechanical support to the contused spinal cord and supported pro-regenerative macrophage polarization, angiogenesis, axon growth, and neurogenesis in the injured tissue without any exogenous factors or cells. These results motivate further optimization of the NHC and delivery protocol to fully translate the potential of the unique properties of the NHC for treating spinal cord injury.


Asunto(s)
Nanofibras , Traumatismos de la Médula Espinal , Animales , Axones , Hidrogeles , Regeneración Nerviosa , Ratas , Recuperación de la Función , Médula Espinal , Traumatismos de la Médula Espinal/terapia
15.
Cell Transplant ; 28(9-10): 1132-1139, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31304790

RESUMEN

Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent stem cells that can be isolated based on stage-specific embryonic antigen-3 (SSEA-3), a pluripotent stem cell-surface marker. However, their capacities for survival, neurotrophic factor secretion, and neuronal and glial differentiation are unclear in rodents. Here we analyzed mouse adipose tissue-derived Muse cells in vitro. We collected mesenchymal stem cells (MSCs) from C57BL/6 J mouse adipose tissue and separated SSEA-3+, namely Muse cells, and SSEA-3-, non-Muse cells, to assess self-renewability; pluripotency marker expression (Nanog, Oct3/4, Sox2, and SSEA-3); spontaneous differentiation into endodermal, mesodermal, and ectodermal lineages; and neural differentiation capabilities under cytokine induction. Neurally differentiated Muse and non-Muse cell functions were assessed by calcium imaging. Antioxidant ability was measured to assess survival under oxidative stress. Brain-derived neurotrophic factor (BDNF), vascular endothelial cell growth factor (VEGF), and hepatocyte growth factor (HGF) secretion were analyzed in enzyme-linked immunosorbent assays. SSEA-3+ Muse cells (6.3 ± 1.9% of mouse adipose-MSCs), but not non-Muse cells, exhibited self-renewability, spontaneous differentiation into the three germ layers, and differentiation into cells positive for Tuj-1 (27 ± 0.9%), O4 (17 ± 3.4%), or GFAP (23 ± 1.3%) under cytokine induction. Neurally differentiated Muse cells responded to KCl depolarization with greater increases in cytoplasmic Ca2+ levels than non-Muse cells. Cell survival under oxidative stress was significantly higher in Muse cells (50 ± 2.7%) versus non-Muse cells (22 ± 2.8%). Muse cells secreted significantly more BDNF, VEGF, and HGF (273 ± 12, 1479 ± 7.5, and 6591 ± 1216 pg/mL, respectively) than non-Muse cells (133 ± 4.0, 1165 ± 20, and 2383 ± 540 pg/mL, respectively). Mouse Muse cells were isolated and characterized for the first time. Muse cells showed greater pluripotency-like characteristics, survival, neurotrophic factor secretion, and neuronal and glial-differentiation capacities than non-Muse cells, indicating that they may have better neural-regeneration potential.


Asunto(s)
Tejido Adiposo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Diferenciación Celular , Factor de Crecimiento de Hepatocito/biosíntesis , Células Madre Mesenquimatosas/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Tejido Adiposo/citología , Animales , Calcio/metabolismo , Señalización del Calcio , Femenino , Células Madre Mesenquimatosas/citología , Ratones , Neuroglía/citología , Neuroglía/metabolismo , Neuronas/citología , Neuronas/metabolismo , Estrés Oxidativo
17.
J Neurotrauma ; 35(12): 1379-1386, 2018 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-29336201

RESUMEN

Mice with a knockout of phospholipase C (PLC)-related inactive protein type 1 (PRIP1-/- mice) display anxiety-like behavior and altered γ-aminobutyric acid (GABA)A-receptor pharmacology. Here, we examined associations between anxiety and motor-function recovery in PRIP1-/- mice after a spinal cord injury (SCI) induced by a moderate contusion injury at the 10th thoracic level. Uninjured PRIP1-/- mice showed less distance than wild-type (WT) mice in the center 25% in an open field test (OFT), indicating anxiety-like behavior. Anxiety behavior increased in both WT and PRIP1-/- mice after SCI. WT and PRIP1-/- mice were completely paralyzed on day 1 after SCI, but gradually recovered until reaching a plateau at ∼4 weeks. After SCI, the PRIP1-/- mice had significantly greater motor dysfunction than the WT mice. In WT mice after SCI, the percentage of distance spent in the center 25% of the OFT was correlated with the OFT distance traveled and velocity, and with the reaction time in a plantar pressure-sensitivity mechanical test. In PRIP1-/- mice after SCI, the percentage of distance spent in the center 25% of the OFT was correlated with the OFT distance traveled and with the latency to fall in the rotarod test. Six weeks after SCI, ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) expressions were elevated at the lesion epicenter in PRIP1-/- mice, and spinal cord atrophy and demyelination were more severe than in WT mice. The axonal fiber development was also decreased in PRIP1-/- mice, consistent with the poor motor-function recovery after SCI in these mice.


Asunto(s)
Ansiedad/complicaciones , Recuperación de la Función , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/psicología , Animales , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Coactivadores de Receptor Nuclear/deficiencia
18.
Artículo en Inglés | MEDLINE | ID: mdl-27579001

RESUMEN

PURPOSE: We encountered a case where an infection with group A streptococcus (GAS; ie, Streptococcus pyogenes) initially caused primary peritonitis and then subsequently caused streptococcal toxic shock syndrome. The patient's life was likely saved by an emergency laparotomy followed by extensive peritoneal lavage and drainage. CASE PRESENTATION: A 40-year-old woman was admitted to the Emergency Department for lower abdominal pain and numbness in the extremities. She presented with systemic inflammatory response syndrome. An emergency laparotomy was performed, and ascites that resembled pus and general peritonitis were noted. Peritoneal lavage and drainage were performed, and GAS was isolated from peritoneal fluid. Gram staining of cervical polyp specimens revealed Gram-positive bacteria. CONCLUSIONS: The patient was diagnosed with streptococcal toxic shock syndrome due to an ascending GAS infection originating from vagina.

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