Schwann cells naturally support axonal regeneration after injury in the peripheral nervous system, and have also shown a significant, albeit limited, ability to support axonal growth and remyelination after grafting to the central nervous system (CNS). It is possible that Schwann cell-induced axonal growth in the CNS could be substantially increased by genetic manipulation to secrete augmented amounts of neurotrophic factors. To test this hypothesis, cultured primary adult rat Schwann cells were genetically modified using retroviral vectors to produce and secrete high levels of human nerve growth factor (NGF). These cells were then grafted to the midthoracic spinal cords of adult rats. Findings were compared to animals that received grafts of nontransduced Schwann cells. Spinal cord lesions were not placed prior to grafting because the primary aim of this study was to examine features of grafted Schwann cell survival, growth, and effects on host axons. In vitro prior to grafting, Schwann cells secreted 1.5+/-0.1 ng human NGF/ml/10(6) cells/day. Schwann cell transplants readily survived for 2 wk to 1 yr after in vivo placement. Some NGF-transduced grafts slowly increased in size over time compared to nontransduced grafts; the latter remained stable in size. NGF-transduced transplants were densely penetrated by primary sensory nociceptive axons originating from the dorsolateral fasciculus of the spinal cord, whereas control grafts showed significantly fewer penetrating sensory axons. Over time, Schwann cell grafts also became penetrated by TH- and DBH-labeled axons of putative coerulospinal origin, unlike control cell grafts. Ultrastructurally, axons in both graft types were extensively myelinated by Schwann cells. Grafted animals showed no changes in gross locomotor function. In vivo expression of the human NGF transgene was demonstrated for periods of at least 6 m. These findings demonstrate that primary adult Schwann cells 1) can be transduced to secrete augmented levels of neurotrophic factors, 2) survive grafting to the CNS for prolonged time periods, 3) elicit robust growth of host neurotrophin-responsive axons, 4) myelinate CNS axons, and 5) express the transgene for prolonged time periods in vivo. Some grafts slowly enlarge over time, a feature that may be attributable to the propensity of Schwann cells to immortalize after multiple passages. Transduced Schwann cells merit further study as tools for promoting CNS regeneration.
Police duties place many officers at risk of traumatic stress and subsequent development of symptoms of post‐traumatic stress disorder (PTSD). A survey of 527 New Zealand Police officers was carried out to investigate the prevalence of PTSD and its relationship with traumatic experiences, both on and off the job. The results showed that the prevalence of PTSD in the New Zealand Police is comparable with that in other civilian populations who have experienced trauma. The number of reported traumatic events was positively correlated with the intensity of PTSD symptoms. Traumatic events experienced while on duty as a police officer were more strongly correlated with PTSD, and chronic experience of the same type of event predicted higher PTSD scores. The results are discussed in terms of implications for police organizations whose members are at risk of multiple traumatic experiences.
Autism spectrum disorder (ASD) is categorized by deficits in social communication and interaction, alongside repetitive, restrictive behaviors or interests (RRBIs). Previous research supports the efficacy of virtual reality (VR) to train a variety of specific skills (i.e., riding a bus or crossing the street) as well as more complex social skills, such as emotion recognition and functional communication. The present reports the implementation of a VR-based air travel functional communication activity in five children diagnosed with ASD. Using an iPhone X and Google Cardboard device, researchers delivered the VR intervention once per week for 3 weeks to each participant. During these interventions, researchers measured activity completion ability on a 4-point scale. At week 4, all children participated in a real-world air travel rehearsal at the San Diego International Airport. Parents were asked to rate their child's air travel abilities before week 1 and after week 4. All children improved their air travel skills from pre-to postintervention, reflected in both the researchers' and parents' observations. All children navigated the real-world airport under their own power. This preliminary report suggests the efficacy of VR to teach basic air travel skills to young children diagnosed with autism. Clinician observations regarding attention to the VR and strategies for helping participants accept the intervention technique are discussed. Future iterations of this program will require larger sample sizes and more robust clinical measurements-such as communication samples and physiological monitoring.
Previously we reported that grafts of cells genetically modified to produce human nerve growth factor (hNGF) promoted specific and robust sprouting of spinal sensory, motor, and noradrenergic axons. In the present study we extend these investigations to assess NGF effects on corticospinal motor axons and on functional outcomes after spinal cord injury. Fibroblasts from adult rats were transduced to express human NGF; control cells were not genetically modified. Fibroblasts were then grafted to sites of midthoracic spinal cord dorsal hemisection lesions. Three months later, recipients of NGF-secreting grafts showed deficits on conditioned locomotion over a wire mesh that did not differ in extent from control-lesioned animals. On histological examination, NGF-secreting grafts elicited specific sprouting from spinal primary sensory afferent axons, local motor axons, and putative cerulospinal axons as previously reported, but no specific responses from corticospinal axons. Axons responding to NGF robustly penetrated the grafts but did not exit the grafts to extend to normal innervation territories distal to grafts. Grafted cells continued to express NGF protein through the experimental period of the study. These findings indicate that 1) spinal cord axons show directionally sensitive growth responses to neurotrophic factors, 2) growth of axons responding to a neurotrophic factor beyond an injury site and back to their natural target regions will likely require delivery of concentration gradients of neurotrophic factors toward the target, 3) corticospinal axons do not grow toward a cellular source of NGF, and 4) functional impairments are not improved by strictly local sprouting response of nonmotor systems.
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