Economic Evaluation of Telerobotic Ultrasound Technology to Remotely Provide Ultrasound Services in Rural and Remote Communities.

INTRODUCTION: Telerobotic ultrasound technology allows radiologists and sonographers to remotely provide ultrasound services in underserved areas. This study aimed to compare costs associated with using telerobotic ultrasound to provide ultrasound services in rural and remote communities to costs associated with alternate models. METHODS: A cost-minimization approach was used to compare four ultrasound service delivery models: telerobotic ultrasound (Model 1), telerobotic ultrasound and an itinerant sonographer (Model 2), itinerant sonographer without telerobotic ultrasound (Model 3), and travel to another community for all exams (Model 4). In Models 1-3, travel was assumed when exams could not be successfully performed telerobotically or by an itinerant sonographer. A publicly funded healthcare payer perspective was used for the reference case and a societal perspective was used for a secondary non-reference case. Costs were based on the literature and experience using telerobotic ultrasound in Saskatchewan, Canada. Costs were expressed in 2020 Canadian dollars. RESULTS: Average cost per ultrasound exam was $342, $323, $368, and $478 for Models 1, 2, 3, and 4, respectively, from a publicly funded healthcare payer perspective, and $461, $355, $447, and $849, respectively, from a societal perspective. In one-way sensitivity analyses, Model 2 was the lowest cost from a payer perspective for communities with population >2075 people, distance >350 km from the nearest ultrasound facility, or >47% of the population eligible for publicly funded medical transportation. CONCLUSION: Health systems may wish to consider solutions such as telerobotic ultrasound and itinerant sonographers to reduce healthcare costs and improve access to ultrasound in rural and remote communities.

Use of Virtual Care Strategies to Join Multidisciplinary Teams Evaluating Work-Related Injuries in Rural Residents.

Background: Rural injured workers requiring multidisciplinary assessments for musculoskeletal disorders face health access disparities, which include travel to urban centers. Virtual care can enhance access to multidisciplinary team care for musculoskeletal conditions in rural areas. Materials and Methods: A retrospective chart audit of 136 multidisciplinary assessment reports of injured workers was conducted. Comprehensive management recommendations from the health care assessment team were extracted for analysis. The health care team used virtual technologies to join with patients and at least one local rural health practitioner in one of three locations. Remote presence robotics (RPR; Xpress Technology™) or laptop-based telehealth was used to complete the assessments. Results: RPR were used in 46% of assessments over two sites, with 54% using laptop-based telehealth at a third site. Frequencies of team members' assessment using technologies were as follows: physical therapist (100%), psychologist (78%), plastic surgeon (8%), and physician (43%). Spine (42%) and shoulder (32%) disorders were the most common problems. Most workers (79%) were 3 or more months postinjury. The most common management recommendation was the need for daily comprehensive rehabilitation care (76%). Travel time was saved by 89% of participants. Conclusions: Virtual care was used to unite multidisciplinary assessment teams for the evaluation of injured rural workers with complex musculoskeletal injuries. Future research recommendations include comparing between virtual and fully in-person multidisciplinary assessment and recommendation findings, and evaluation of patient and practitioner experiences with comprehensive virtual team assessments.

Sociodemographic and Geographic Factors Associated With Non-Obstetrical Ultrasound Imaging Utilization: A Population-Based Study.

OBJECTIVE: Ultrasound is one of the most commonly used imaging modalities, though some populations face barriers in accessing ultrasound services, potentially resulting in disparities in utilization. The objective of this study was to assess the association between sociodemographic and geographic factors and non-obstetrical ultrasound utilization in the province of Saskatchewan, Canada. METHODS: All non-obstetrical ultrasound exams performed from 2014 to 2018 in Saskatchewan, Canada were retrospectively identified from province-wide databases. Univariate and multivariate Poisson regression analyses were performed to assess the association between ultrasound utilization and sex, age, First Nations status, Charlson Comorbidity Index, urban vs. rural residence, geographic remoteness, and neighborhood income. RESULTS: A total of 1,324,846 individuals (5,857,044 person-years) were included in the analysis. Female sex (adjusted incidence rate ratio [aIRR], 2.20; 95% confidence interval [CI], 2.19-2.22), age (aIRR, 4.97; 95% CI, 4.90-5.05 for ≥57 years vs. <11 years), comorbidities (aIRR, 4.36 for Charlson Comorbidity Index >10 vs. 0; 95% CI, 3.78-5.03), and higher neighborhood income (aIRR, 1.04; 95% CI, 1.02-1.05 for highest vs. lowest quintile) were associated with higher rates of ultrasound utilization. Individuals who were status First Nations (aIRR, 0.91; 95% CI, 0.90-0.92) or resided in geographically remote areas (aIRR, 0.87 for most vs. least remote; 95% CI, 0.83-0.91) had lower rates of ultrasound utilization. Individuals who lived in a rural area also had lower rates of ultrasound utilization (aIRR, 0.93; 95% CI, 0.92-0.94). CONCLUSION: Substantial disparities exist in non-obstetrical ultrasound utilization among individuals in low-income neighborhoods, status First Nations individuals, and individuals in rural and remote communities.

Telerobotic Sonography for Remote Diagnostic Imaging: Narrative Review of Current Developments and Clinical Applications.

Access to sonographers and sonologists is limited in many communities around the world. Telerobotic sonography (robotic ultrasound) is a new technology to increase access to sonography, providing sonographers and sonologists the ability to manipulate an ultrasound probe from a distant location and remotely perform ultrasound examinations. This narrative review discusses the development of telerobotic ultrasound systems, clinical studies evaluating the feasibility and diagnostic accuracy of telerobotic sonography, and emerging use of telerobotic sonography in clinical settings. Telerobotic sonography provides an opportunity to provide real-time ultrasound examinations to underserviced rural and remote communities to increase equity in the delivery of diagnostic imaging.

Canadian Assessment of Deep Brain Stimulation Access: The Canada Study.

BACKGROUND: The Canada Health Act requires reasonable access to all medically necessary therapies. No information is available to assess the current access to neuromodulation across Canada. This study quantifies the current rate of deep brain stimulation (DBS) for the entire country of Canada. Analyses were performed to determine whether there were differences in access based on provincial or territorial location, rural or non-rural region, or socioeconomic status. METHODS: All implanted DBS devices in Canada over a 2-year epoch (January 2015 to December 2016) were supplied by either Boston Scientific or Medtronic. Investigators received anonymized data from these companies, including patient age and home residence region. The 2016 Statistics Canada census data were used to determine the rate of DBS surgery and whether access was related to provincial location, rural versus non-rural region or socioeconomic status. RESULTS: A total of 722 patients were studied. The rate of DBS surgery for the entire country was ten per million population per year. Saskatchewan was significantly above (374%) the national average, whereas Quebec (40%) and Newfoundland & Labrador (32%) were significantly below the national average. No patients from the three territories received DBS. There were no significant differences in access from rural versus non-rural areas or in regions within provinces with different socioeconomic status. CONCLUSIONS: This is the first study to quantify all patients receiving DBS within an entire country. The current rate of DBS surgery within Canada is ten cases per million per year. Statistically significant regional differences were discovered and discussed.

A Crossover Comparison of Standard and Telerobotic Approaches to Prenatal Sonography.

OBJECTIVES: To determine the feasibility of a telerobotic approach to remotely perform prenatal sonographic examinations. METHODS: Thirty participants were prospectively recruited. Participants underwent a limited examination (assessing biometry, placental location, and amniotic fluid; n = 20) or a detailed examination (biometry, placental location, amniotic fluid, and fetal anatomic survey; n = 10) performed with a conventional ultrasound system. This examination was followed by an equivalent examination performed with a telerobotic ultrasound system, which enabled sonographers to remotely control all ultrasound settings and fine movements of the ultrasound transducer from a distance. Telerobotic images were read independently from conventional images. RESULTS: The mean gestational age ± SD of the 30 participants was 22.9 ± 5.3 weeks. Paired-sample t tests showed no statistically significant difference between conventional and telerobotic measurements of fetal head circumference, biparietal diameter, or single deepest vertical pocket of amniotic fluid; however, a small but statistically significant difference was observed in measurements of abdominal circumference and femur length (P < .05). Intraclass correlations showed excellent agreement (>0.90) between telerobotic and conventional measurements of all 4 biometric parameters. Of 21 fetal structures included in the anatomic survey, 80% of the structures attempted across all patients were sufficiently visualized by the telerobotic system (range, 57%-100% per patient). Ninety-seven percent of patients strongly or somewhat agreed that they would be willing to have another telerobotic examination in the future. CONCLUSIONS: A telerobotic approach is feasible for remotely performing prenatal sonographic examinations. Telerobotic sonography (robotic telesonography) may allow for the development of satellite ultrasound clinics in rural, remote, or low-volume communities, thereby increasing access to prenatal imaging in underserved communities.

Remote Presence Robotic Technology Reduces Need for Pediatric Interfacility Transportation from an Isolated Northern Community.

BACKGROUND: Providing acutely ill children in isolated communities access to specialized care is challenging. This study aimed to evaluate remote presence robotic technology (RPRT) for enhancing pediatric remote assessments, expediting initiation of treatment, refining triaging, and reducing the need for transport. METHODS: We conducted a pilot prospective observational study at a primary/urgent care clinic in an isolated northern community. Participants (n = 38) were acutely ill children <17 years presenting to the clinic, whom local healthcare professionals had considered for interfacility transportation (IFT). Participants were assessed and managed by a tertiary center pediatric intensivist through a remote presence robot. The intensivist triaged participants to either remain at the clinic or be transported to regional/tertiary care. Controls from a pre-existing local transport database were matched using propensity scoring. The primary outcome was the number of IFTs among participants versus controls. RESULTS: Fourteen of 38 (37%) participants required transport, whereas all controls were transported (p < 0.0001). Six of 14 (43%) transported participants were triaged to a nearby regional hospital, while no controls were regionalized (p = 0.0001). All participants who remained at the clinic stayed <24 h, and were matched to controls who stayed 4.9 days in tertiary care (p < 0.001). There was no statistically significant difference in hospital length of stay between transported participants and controls (6.0 vs. 5.7 days). CONCLUSIONS: RPRT reduced the need for specialized pediatric IFT, while enabling regionalization when appropriate. This study may have implications for the broader implementation of RPRT, while reducing costs to the healthcare system.

Initial Experience Using a Telerobotic Ultrasound System for Adult Abdominal Sonography.

PURPOSE: The study sought to assess the feasibility of performing adult abdominal examinations using a telerobotic ultrasound system in which radiologists or sonographers can control fine movements of a transducer and all ultrasound settings from a remote location. METHODS: Eighteen patients prospectively underwent a conventional sonography examination (using EPIQ 5 [Philips] or LOGIQ E9 [GE Healthcare]) followed by a telerobotic sonography examination (using the MELODY System [AdEchoTech] and SonixTablet [BK Ultrasound]) according to a standardized abdominal imaging protocol. For telerobotic examinations, patients were scanned remotely by a sonographer 2.75 km away. Conventional examinations were read independently from telerobotic examinations. Image quality and acceptability to patients and sonographers was assessed. RESULTS: Ninety-two percent of organs visualized on conventional examinations were sufficiently visualized on telerobotic examinations. Five pathological findings were identified on both telerobotic and conventional examinations, 3 findings were identified using only conventional sonography, and 2 findings were identified using only telerobotic sonography. A paired sample t test showed no significant difference between the 2 modalities in measurements of the liver, spleen, and diameter of the proximal aorta; however, telerobotic assessments overestimated distal aorta and common bile duct diameters and underestimated kidney lengths (P values < .05). All patients responded that they would be willing to have another telerobotic examination. CONCLUSIONS: A telerobotic ultrasound system is feasible for performing abdominal ultrasound examinations at a distant location with minimal training and setup requirements and a moderate learning curve. Telerobotic sonography (robotic telesonography) may open up the possibility of remote ultrasound clinics for communities that lack skilled sonographers and radiologists, thereby improving access to care.

A Telerobotic Ultrasound Clinic Model of Ultrasound Service Delivery to Improve Access to Imaging in Rural and Remote Communities.

OBJECTIVE: Patients living in many rural and remote areas do not have readily available access to ultrasound services because of a lack of sonographers and radiologists in these communities. The objective of this study was to determine the feasibility of using telerobotic ultrasound to establish a service delivery model to remotely provide access to diagnostic ultrasound in rural and remote communities. METHODS: Telerobotic ultrasound clinics were developed in three remote communities more than 500 km away from our academic medical center. Sonographers remotely performed all ultrasound examinations using telerobotic ultrasound systems, and examinations were subsequently interpreted by radiologists at an academic medical center. Diagnostic performance was assessed by each interpreting radiologist using a standardized reporting form. Patient experience was assessed through quantitative and qualitative analysis of survey responses. Operational challenges and solutions were identified. RESULTS: Eighty-seven telerobotic ultrasound examinations were remotely performed and included in this study, with the most frequent examination types being abdominal (n = 35), first-trimester obstetrical (n = 26), and second-trimester complete obstetrical (n = 12). Across all examination types, 70% of telerobotic ultrasound examinations were sufficient for diagnosis, minimizing travel or reducing wait times for these patients. Ninety-five percent of patients would be willing to have another telerobotic ultrasound examination in the future. Operational challenges were related to technical infrastructure, human resources, and coordination between clinic sites. CONCLUSION: Telerobotic ultrasound can provide access to diagnostic ultrasound services to underserved rural and remote communities without regular ultrasound services, thereby reducing disparities in access to care and improving health equity.

Telerobotic ultrasound to provide obstetrical ultrasound services remotely during the COVID-19 pandemic.

INTRODUCTION: Obstetrical ultrasound imaging is critical in identifying at-risk pregnancies and informing clinical management. The coronavirus disease 2019 (COVID-19) pandemic has exacerbated challenges in accessing obstetrical ultrasound for patients in underserved rural and remote communities where this service is not available. This prospective descriptive study describes our experience of providing obstetrical ultrasound services remotely using a telerobotic ultrasound system in a northern Canadian community isolated due to a COVID-19 outbreak. METHODS: A telerobotic ultrasound system was used to perform obstetrical ultrasound exams remotely in La Loche, Canada, a remote community without regular access to obstetrical ultrasound. Using a telerobotic ultrasound system, a sonographer 605 km away remotely controlled an ultrasound probe and ultrasound settings. Twenty-one exams were performed in a five-week period during a COVID-19 outbreak in the community, including limited first-, second- and third-trimester exams (n = 11) and complete second-trimester exams (n = 10). Participants were invited to complete a survey at the end of the telerobotic ultrasound exam describing their experiences with telerobotic ultrasound. Radiologists subsequently interpreted all exams and determined the adequacy of the images for diagnosis. RESULTS: Of 11 limited obstetrical exams, radiologists indicated images were adequate in nine (81%) cases, adequate with some reservations in one (9%) case and inadequate in one (9%) case. Of 10 second-trimester complete obstetrical exams, radiologists indicated images were adequate in two (20%) cases, adequate with some reservations in three (30%) cases and inadequate in five (50%) cases. Second-trimester complete obstetrical exams were limited due to a combination of body habitus, foetal lie and telerobotic technology. DISCUSSION: A telerobotic ultrasound system may be used to answer focused clinical questions such as foetal viability, dating and foetal presentation in a timely manner while minimising patient travel to larger centres and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during the COVID-19 pandemic.

Sociodemographic and Geographic Disparities in Obstetrical Ultrasound Imaging Utilization: A Population-based Study.

RATIONALE AND OBJECTIVES: Obstetrical ultrasound imaging is an important part of prenatal care, though not all patients have readily available access to ultrasound services. This study aimed to assess the association between sociodemographic and geographic factors and (1) having a second trimester complete obstetrical ultrasound and (2) overall obstetrical ultrasound utilization. METHODS: All pregnancies and obstetrical ultrasound exams billed from 2014-2018 in Saskatchewan, Canada were identified from province-wide databases. Generalized estimating equation (GEE) models with binomial and Poisson distributions were used to identify factors associated with having a second trimester ultrasound and overall obstetrical ultrasound utilization, respectively. RESULTS: 80,536 pregnancies from 57,881 individuals were included. Of 57,186 pregnancies carried to ≥23 weeks, a second trimester ultrasound was performed in 50,180 (87.7%). Patients living in rural areas (adjusted odds ratio [aOR], 0.70; 95% confidence interval [CI], 0.63-0.77; p <0.0001), remote areas (aOR, 0.35 for greatest vs. least remoteness level; 95% CI, 0.32-0.39; p <0.0001), and status First Nations individuals (aOR, 0.50; 95% CI, 0.46-0.53; p <0.0001) were less likely to have a second trimester ultrasound. Patients living in higher income neighbourhoods (aOR, 1.86 for highest vs. lowest quintile; 95% CI, 1.62-2.13; p <0.0001) were more likely to have a second trimester ultrasound. GEE Poisson regression analysis demonstrated these same factors, except rural residence, were associated with overall obstetrical ultrasound utilization. CONCLUSION: Substantial disparities in obstetrical ultrasound utilization exist among patients in remote geographic areas, Indigenous peoples, and patients in low income neighbourhoods. Addressing barriers which these demographic groups face in accessing ultrasound imaging is critical to ensure health equity.

Implementation and evaluation of a pilot antenatal ultrasound imaging programme using tele-ultrasound in Ethiopia.

INTRODUCTION: Ultrasound imaging is an important aspect of antenatal care, though access to antenatal ultrasound imaging is limited in many developing countries. The objective of this study was to evaluate a pilot programme which aimed to improve access to antenatal ultrasound for rural Ethiopians through enhanced training of healthcare providers (including midwives, nurses and clinical officers) with support remotely provided by obstetricians using a tele-ultrasound platform. METHODS: Thirteen healthcare providers in the North Shoa Zone in Ethiopia completed training to enable them to perform antenatal ultrasound with the remote supervision of an obstetrician via a tele-ultrasound platform. Pregnant women attending an antenatal appointment at two facilities were offered an antenatal ultrasound exam performed by one of the healthcare providers. Image interpretations between obstetricians and healthcare providers were compared. Participants and healthcare providers were invited to complete a questionnaire regarding their experience with tele-ultrasound, and participants, healthcare providers and obstetricians were interviewed regarding their experience with the tele-ultrasound pilot programme. RESULTS: 2795 pregnant women had an antenatal ultrasound exam. Of 100 exams randomly selected to assess concordance between healthcare providers' and obstetricians' image interpretations, concordance ranged from 79% to 100% for each parameter assessed. 99.4% of participants surveyed indicated that they would recommend antenatal ultrasound using tele-ultrasound to friends and family. Themes relating to participants' experiences of having a tele-ultrasound exam were reduced travel and cost, equivalence in quality of virtual care to in-person care and empowerment through diagnostic information. CONCLUSION: Healthcare provider-performed antenatal ultrasound - supported by obstetricians via tele-ultrasound - showed high levels of concordance, was well-received by participants and provided rural Ethiopian women with enhanced access to antenatal imaging.

Access to ultrasound imaging: A qualitative study in two northern, remote, Indigenous communities in Canada.

Ultrasound imaging is an essential component of healthcare services. This study sought to explore perceptions of access, and factors which shape access, to ultrasound imaging in two northern, remote, Indigenous communities in Canada. Using interpretive description as a methodological approach and a multi-dimensional conceptualisation of access to care as a theoretical framework, 15 semi-structured interviews were conducted in the northern Canadian communities of Stony Rapids and Black Lake, Saskatchewan. All participants had an obstetrical or non-obstetrical ultrasound exam performed in the past 10 years. Interviews were audio recorded and interview transcripts were analysed using constant comparative analysis. Geographic isolation from imaging facilities was a central barrier to participants accessing ultrasound imaging. Other barriers became apparent when participants had to travel for ultrasound, including fear of air travel, isolation from family, financial means, and unfamiliarity with larger cities. Barriers such as family and work responsibilities were exacerbated by the barrier of geography. Participants overcame these barriers as they were motivated by potential diagnostic benefits of ultrasound imaging. This study highlights disparities in access to ultrasound for northern, remote, Indigenous populations. Future efforts to improve access to imaging should consider barriers of distance to imaging facilities and strategies to bridge these barriers.

Bioreactor expansion of human neural precursor cells in serum-free media retains neurogenic potential.

Human neural precursor cells (hNPCs), harvested from somatic tissue and grown in vitro, may serve as a source of cells for cell replacement strategies aimed at treating neurodegenerative disorders such as Parkinson's disease (PD), Huntington's disease (HD), and intractable spinal cord pain. A crucial element in a robust clinical production method for hNPCs is a serum-free growth medium that can support the rapid expansion of cells while retaining their multipotency. Here, we report the development of a cell growth medium (PPRF-h2) for the expansion of hNPCs, achieving an overall cell-fold expansion of 10(13) over a period of 140 days in stationary culture which is significantly greater than other literature results. More importantly, hNPC expansion could be scaled-up from stationary culture to suspension bioreactors using this medium. Serial subculturing of the cells in suspension bioreactors resulted in an overall cell-fold expansion of 7.8 x 10(13) after 140 days. These expanded cells maintained their multipotency including the capacity to generate large numbers of neurons (about 60%). In view of our previous studies regarding successful transplantation of the bioreactor-expanded hNPCs in animal models of neurological disorders, these results have demonstrated that PPRF-h2 (containing dehydroepiandrosterone, basic fibroblast growth factor and human leukemia inhibitory factor) can successfully facilitate the production of large quantities of hNPCs with potential to be used in the treatment of neurodegenerative disorders.

Preliminary clinical algorithm to optimise remote delivery of paediatric concussion care in Canada's North.

Concussion is a form of traumatic brain injury that affects thousands of children and adolescents across Canada annually. With timely access to comprehensive medical care, the majority of patients with acute concussion will recover within 1-4 weeks. Those who develop persistent post-concussion symptoms often benefit from early recognition and referral to multi-disciplinary concussion clinics that have the personnel and resources to meet their complex needs. Youth who live in remote and isolated communities within Canada's North, a significant proportion of whom are Indigenous, face unique barriers and obstacles to accessing primary and specialised concussion care. Although telemedicine has recently emerged as a tool that can help address these gaps in care, there are presently no clinical guidelines or tools available to assist multi-disciplinary concussion clinics in providing remote concussion care to these medically underserved patients. Here we incorporate literature from a scoping review and our early institutional experience to present an evidence-informed preliminary clinical algorithm and resources to help guide and optimise remote paediatric concussion care delivery in Canada's North. We also discuss how innovative technologies and partnerships can be leveraged to enhance the delivery of safe, equitable, cost-effective and culturally appropriate care to these communities.

Enhancing access to care in northern rural communities via telehealth.

The cost of providing health care in northern Canada is higher than the rest of Canada. Telehealth has the potential to reduce health care expenditures. Yet this is still underutilised in Canada and globally. This paper describes the services provided through telehealth in some northern regions of Canada. It provides recommendations on the requirements for setting up real presence telehealth and how utilisation can be enhanced. Telehealth offers potential benefits for health outcomes by increasing access to healthcare, and reducing expenditures.

Spinal GABAergic transplants attenuate mechanical allodynia in a rat model of neuropathic pain.

Injury to the spinal cord or peripheral nerves can lead to the development of allodynia due to the loss of inhibitory tone involved in spinal sensory function. The potential of intraspinal transplants of GABAergic cells to restore inhibitory tone and thus decrease pain behaviors in a rat model of neuropathic pain was investigated. Allodynia of the left hind paw was induced in rats by unilateral L5- 6 spinal nerve root ligation. Mechanical sensitivity was assessed using von Frey filaments. Postinjury, transgenic fetal green fluorescent protein mouse GABAergic cells or human neural precursor cells (HNPCs) expanded in suspension bioreactors and differentiated into a GABAergic phenotype were transplanted into the spinal cord. Control rats received undifferentiated HNPCs or cell suspension medium only. Animals that received either fetal mouse GABAergic cell or differentiated GABAergic HNPC intraspinal transplants demonstrated a significant increase in paw withdrawal thresholds at 1 week post-transplantation that was sustained for 6 weeks. Transplanted fetal mouse GABAergic cells demonstrated immunoreactivity for glutamic acid decarboxylase and GABA that colocalized with green fluorescent protein. Intraspinally transplanted differentiated GABAergic HNPCs demonstrated immunoreactivity for GABA and beta-III tubulin. In contrast, intraspinal transplantation of undifferentiated HNPCs, which predominantly differentiated into astrocytes, or cell suspension medium did not affect any behavioral recovery. Intraspinally transplanted GABAergic cells can reduce allodynia in a rat model of neuropathic pain. In addition, HNPCs expanded in a standardized fashion in suspension bioreactors and differentiated into a GABAergic phenotype may be an alternative to fetal cells for cell-based therapies to treat chronic pain syndromes.

Duration of lipid peroxidation after acute spinal cord injury in rats and the effect of methylprednisolone.

OBJECT: Oxidative stress leading to lipid peroxidation is a major cause of secondary injury following spinal cord injury (SCI). The objectives of this study were to determine the duration of lipid peroxidation following acute SCI and the efficacy of short-and long-term administration of methylprednisolone on decreasing lipid peroxidation. METHODS: A total of 226 female Wistar rats underwent clip-compression induced SCI. In the first part of the study, spinal cords of untreated rats were assayed colorimetrically for malondialdehyde (MDA) to determine lipid peroxidation levels at various time points between 0 and 10 days. In the second part of the study, animals were treated with methylprednisolone for either 24 hours or 7 days. Control animals received equal volumes of normal saline. Treated and control rats were killed at various time points between 0 and 7 days. RESULTS: The MDA levels initially peaked 4 hours postinjury. By 12 hours, the MDA levels returned to baseline. A second increase was observed from 24 hours to 5 days. Both peak values differed statistically from the trough values (p < 0.008). The methylprednisolone reduced MDA levels (p < 0.04) within 12 hours of injury. No effect was seen at 24 hours or later. CONCLUSIONS: The results of this study indicate that oxidative stress persists for 5 days following SCI in rats, and although methylprednisolone reduces MDA levels within the first 12 hours, it has no effect on the second lipid peroxidation peak.

Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats.

OBJECT: Fetal tissue transplantation for Parkinson disease (PD) has demonstrated promising results in experimental and clinical studies. However, the widespread clinical application of this therapeutic approach is limited by a lack of fetal tissue. Human neural precursor cells (HNPCs) are attractive candidates for transplantation because of their long-term proliferation activity. Furthermore, these cells can be reproducibly expanded in a standardized fashion in suspension bioreactors. In this study the authors sought to determine whether the survival, differentiation, and migration of HNPCs after transplantation depended on the region of precursor cell origin, intracerebral site of transplantation, and duration of their expansion. METHODS: Human neural precursor cells were isolated from the telencephalon, brainstem, ventral mesencephalon, and spinal cord of human fetuses 8-10 weeks of gestational age, and their differentiation potential characterized in vitro. After expansion in suspension bioreactors, the HNPCs were transplanted into the striatum and substantia nigra of parkinsonian rats. Histological analyses were performed 7 weeks posttransplantation. RESULTS: The HNPCs isolated from various regions of the neuraxis demonstrated diverse propensities to differentiate into astrocytes and neurons and could all successfully expand under standardized conditions in suspension bioreactors. At 7 weeks posttransplantation, survival and migration were significantly greater for HNPCs obtained from the more rostral brain regions. The HNPCs differentiated predominantly into astrocytes after transplantation into the striatum or substantia nigra regions, and thus no behavioral improvement was observed. CONCLUSIONS: Understanding the regional differences in HNPC properties is prerequisite to their application for PD cell restoration strategies.