Journal of Hematotherapy & Stem Cell Research, Dec 1, 2003
Recent evidence suggests that cells from bone marrow can acquire neuroectodermal phenotypes in ce... more Recent evidence suggests that cells from bone marrow can acquire neuroectodermal phenotypes in cell culture or after transplantation in animal models and in the human brain. However, isolation of the bone marrow cell subpopulation with neuronal differentiation potential remains a challenge. To isolate and expand neural progenitors from whole murine bone marrow, bone marrow was obtained from hind limb bone of C57BL6 mice and plated in culture with neuronal medium with basic fibroblast growth factor and epidermal growth factor. After 5-7 days in culture, cellular spheres similar to brain neurospheres appeared either floating or attached to culture dishes. These spheres were collected, dissociated, and expanded. The bone marrow-derived spheres were positive for nestin as assessed by immunocytochemistry and by reverse transcriptase polymerase chain reaction. Thy-1- and Sca-1-positive bone marrow cells selected by magnetic cell sorting resulted in a higher yield of nestin-positive spheres. After exposure to neuronal differentiative medium retinoic acid with and without Sonic hedgehog, cells positive for neuronal markers tubulin III (TuJ-1) and neurofilament (NF) were detected. The mRNA profile of these cells included the expression of TuJ-1, neuronal-specific enolase (NSE), and NF-light chain. To evaluate the in vivo behavior of these cells, spheres derived from bone marrow-derived cells of transgenic green fluorescent protein (GFP) mice were transplanted into newborn mouse brain. Two months later, the mouse neural cortex contained a minor proportion of GFP(+) cells co-expressing neuronal markers (TuJ-1, NF, MAP-2, NeuN). Although cell fusion phenomena with the host cells could not be ruled out, bone marrow-derived neurosphere transplantation could be a strategy for cellular mediated gene therapy.
Traumatic brain injury (TBI) is the leading cause of death and permanent disability in developmen... more Traumatic brain injury (TBI) is the leading cause of death and permanent disability in developmental age. Neurobehavioural symptoms are not uncommon in these patients. The aim of this study was to identify the main neuropsychiatric sequelae of TBI at different ages and study the possible correlations with clinical features in the acute phase and outcome in order to better plan rehabilitative treatment and re-entry into society. Ninety-six post-traumatic patients, ranging from 0-18 years, underwent a complete psychological evaluation protocol at I year from trauma. Patients were divided into three different age groups (0-6 years; 7-13 years; 14-18 years) and received a protocol made up of age-appropriate scales. Different psychological problems were found across the three groups; more frequently younger patients show internalizing problems such as withdrawal and closure, while, with age, behaviour problems become more frequent, characterized by hyperactivity and aggressiveness. Factors that were most predictive of psychological, behaviour and adjustment problems include GOS scores, the degree of impairment on the neurological examination and male gender. Psychological and behavioural problems differ across the three age groups and determine a different outcome, rehabilitation plan and re-entry into society. These problems should, thus, be investigated and treated specifically according to age.
Volume 1B: Extremity; Fluid Mechanics; Gait; Growth, Remodeling, and Repair; Heart Valves; Injury Biomechanics; Mechanotransduction and Sub-Cellular Biophysics; MultiScale Biotransport; Muscle, Tendon and Ligament; Musculoskeletal Devices; Multiscale Mechanics; Thermal Medicine; Ocular Biomechani..., Jun 26, 2013
Neuromuscular diseases as a consequence of brain damage are complex phenomena involving disuse, i... more Neuromuscular diseases as a consequence of brain damage are complex phenomena involving disuse, immobility, brain tissue remodeling and cortical function remapping. They may have various causes and strike any part of the population. The vicious circle leading to a worsening of the patients’ conditions proceeds through muscle shortening by contractures, disruption of the normal reflex behavior and sensory problems, development of spasticity [1]. Physical rehabilitation alone or in association with surgery or pharmacological treatments can be useful in limiting those degenerations. Besides manual rehabilitation, splints and braces are prescribed to control the limb posture and obtain stretching of the muscles. The role of those orthoses is to maintain the paretic limb in a set ‘physiological’ position and let it relax into that posture, in an attempt to reduce muscle rigidity and contractures. However applying a fixed constraint to the limb and waiting for relaxation to take place, may cause discomfort, pain, skin rash, and sundry different complications [2]. Also, any residual voluntary movement is prevented by a fixed-angle splinting. In addition, all these negative characteristics limit tolerability and daily application times. This work presents a different way to promote limb repositioning, based on the application of NiTi-alloy-based dynamic splints, which favor mobility and any residual use of the affected limb. Furthermore it suggests that application of mild contact forces prolonged in time has the advantage of feeling less painful and uncomfortable for the patients, improving overall treatment tolerability.
Persistent post-injury cognitive, academic and behavioural deficits have been documented in child... more Persistent post-injury cognitive, academic and behavioural deficits have been documented in children who sustained severe TBI during the school-age years. The major aim of this study was to examine and follow-up for 2 years the cognitive profile of a sample of post-injured patients (aged 6-16.11), in order to verify to what extent they recovered their intellectual functions after rehabilitation. Twenty-six patients who received a specific neuropsychological treatment and three cognitive evaluations with WISC-III were selected from a pool of 77. This group of patients showed a mild cognitive deficit at baseline, which improved over the 2 years to a borderline level. Despite the improvement in intellectual quotients and single sub-test scores achieved through rehabilitation, different recovery times were seen according to the function under study. The most common deficits are in processing speed, inferential and lexical-semantic skills. Detailed analysis of the WISC-III sub-tests allows for an accurate description of single cognitive functions after TBI. This allows one to make differential diagnoses between functional profiles and plan individualized rehabilitation treatments. Post-injured school-aged patients should receive rehabilitation for a period of at least 2 years, which is the time necessary for an at-least partial reorganization of basic cognitive functions.
SummaryBackground: Acquired brain injury (ABI) may result in lifelong impairment of physical, cog... more SummaryBackground: Acquired brain injury (ABI) may result in lifelong impairment of physical, cognitive, and psychosocial functions. Several rehabilitative treatments are often needed to support walking recovery, thus participants’ engagement becomes a crucial aspect, especially when patients are children. In the last few years, traditional physiotherapy (PT) has been flanked by innovative technologies for rehabilitation in the fields of robotics and Virtual Reality (VR). Preliminary results have shown interesting perspectives in the use of a VR system, the GRAIL (Gait Real-time Analysis Interactive Lab), in improving walking abilities in a small group of children with ABI, although further insights are needed about its use as rehabilitative tool in the pediatric population.Objectives: To evaluate the efficacy of a rehabilitation treatment on a GRAIL system for the improvement of walking abilities, in a group of children suffering from ABI.Methods: 12 children with ABI (study group – SG; mean age = 12.1 ± 3.8 years old) underwent a 10-session treatment with the GRAIL, an instrumented multi-sensor platform based on immersive VR for gait training and rehabilitation in engaging VR environments. Before (T0) and at the end of the treatment (T1), the participants were assessed by means of functional scales (Gross Motor Function Measure (GMFM), Functional Assessment Questionnaire (FAQ), 6-Minute Walk Test (6minWT) and the 3D-Gait Analysis, over ground (OGA) and on GRAIL (GGA).Results: All the participants completed the rehabilitative treatment. The functional evaluations showed an improvement in Gross Motor abilities (GMFM-88, p = 0.008), especially in standing (GMFM-D, p = 0.007) and walking (GMFM-E, p = 0.005), an increase of the endurance (6minWT, p = 0.002), and enhanced autonomy in daily life activities (FAQ, p = 0.025). OGA identified a significant decrease of the Gillette Gait Index for the impaired side and a general increase of symmetry. GGA showed improvements in spatiotemporal parameters and joints range of motion that moved towards normality and symmetry recovery.Conclusions: A 10-session treatment with GRAIL on children with ABI led to improvements in their walking abilities and enhanced their engagement during the training. This is desirable when long life impairments are faced and children’s motor functions have to be regained and it supports the leading role that VR might have in the rehabilitation field.
Prosthetics and Orthotics International, Sep 1, 2010
NiTi is a metal alloy with unconventional functional characteristics: Shape memory and pseudoelas... more NiTi is a metal alloy with unconventional functional characteristics: Shape memory and pseudoelasticity. Its use in the field of rehabilitation is very innovative. This work presents applications in lower limb orthotics. Three different devices were assembled and tested: An equinus gait dynamic splint, a compliant ankle positioning brace, and a dual-mode haptic/active exerciser for the dorsiflexors. Results are derived from technical and preclinical trials. The gait splint improves several walking parameters even better than a traditional flexible ankle-foot orthoses (AFO). In particular, it supports mid-stance and propulsion biomechanics and affects physiological activation of tibialis anterior during swing much less than posterior leaf AFO. The haptic/active exerciser, able to provide dorsiflexion through a suitable articular range, could be controlled on the basis of minimal surface electromyo-graphic (sEMG) signals, suggesting its use as an aid for early active workouts as soon as patients start to recover voluntary control of tibialis anterior. Further evidence must be sought in future to confirm for the ankle joint the promising results obtained in repositioning applications in prior upper limb studies. The work done so far on the tested prototypes is encouraging: Material characteristics and dimensioning will be optimized so that customized NiTi devices can be prescribed to best meet individual patients' requirements.
The Gait Real-time Analysis Interactive Lab (GRAIL) is an instrumented multi-sensor platform base... more The Gait Real-time Analysis Interactive Lab (GRAIL) is an instrumented multi-sensor platform based on immersive virtual reality for gait training and rehabilitation. Few studies have been included GRAIL to evaluate gait patterns in normal and disabled people and to improve gait in adults, while at our knowledge no evidence on its use for the rehabilitation of children is available. In this study, 4 children suffering from acquired brain injury (ABI) underwent a 5 session treatment with GRAIL, to improve walking and balance ability in engaging VR environments. The first and the last sessions were partially dedicated to gait evaluation. Results are promising: improvements were recorded at the ankle level, selectively at the affected side, and at the pelvic level, while small changes were measured at the hip and knee joints, which were already comparable to healthy subjects. All these changes also conveyed advances in the symmetry of the walking pattern. In the next future, a longer intervention will be proposed and more children will be enrolled to strongly prove the effectiveness of GRAIL in the rehabilitation of children with ABI.
Volume 1A: Abdominal Aortic Aneurysms; Active and Reactive Soft Matter; Atherosclerosis; BioFluid Mechanics; Education; Biotransport Phenomena; Bone, Joint and Spine Mechanics; Brain Injury; Cardiac Mechanics; Cardiovascular Devices, Fluids and Imaging; Cartilage and Disc Mechanics; Cell and Tiss..., 2013
ABSTRACT The ankle joint is a fundamental element in the biomechanical system of locomotion. When... more ABSTRACT The ankle joint is a fundamental element in the biomechanical system of locomotion. When its functions are impaired, due to neurological insult such as brain trauma or a stroke, severe disability and loss of personal independence may ensue. For this reason, great care is given to the physical rehabilitation of the lower limb. On the other hand, it is often the case that only a limited amount of time can be specifically devoted to the ankle joint manipulation during routine rehabilitation sessions. Furthermore, early initiation of active workout may be impossible for patients showing paresis; even passive exercise is often delivered to a minimal degree while the general conditions of the patients impose that they are kept bedridden. The delay in commencing rehabilitation may have negative consequences in terms of detrimental changes in tissue properties, deafferentation through lack of proprioceptive stimulation, learned non-use, and, ultimately, spastic paresis [1].
Journal of Hematotherapy & Stem Cell Research, Dec 1, 2003
Recent evidence suggests that cells from bone marrow can acquire neuroectodermal phenotypes in ce... more Recent evidence suggests that cells from bone marrow can acquire neuroectodermal phenotypes in cell culture or after transplantation in animal models and in the human brain. However, isolation of the bone marrow cell subpopulation with neuronal differentiation potential remains a challenge. To isolate and expand neural progenitors from whole murine bone marrow, bone marrow was obtained from hind limb bone of C57BL6 mice and plated in culture with neuronal medium with basic fibroblast growth factor and epidermal growth factor. After 5-7 days in culture, cellular spheres similar to brain neurospheres appeared either floating or attached to culture dishes. These spheres were collected, dissociated, and expanded. The bone marrow-derived spheres were positive for nestin as assessed by immunocytochemistry and by reverse transcriptase polymerase chain reaction. Thy-1- and Sca-1-positive bone marrow cells selected by magnetic cell sorting resulted in a higher yield of nestin-positive spheres. After exposure to neuronal differentiative medium retinoic acid with and without Sonic hedgehog, cells positive for neuronal markers tubulin III (TuJ-1) and neurofilament (NF) were detected. The mRNA profile of these cells included the expression of TuJ-1, neuronal-specific enolase (NSE), and NF-light chain. To evaluate the in vivo behavior of these cells, spheres derived from bone marrow-derived cells of transgenic green fluorescent protein (GFP) mice were transplanted into newborn mouse brain. Two months later, the mouse neural cortex contained a minor proportion of GFP(+) cells co-expressing neuronal markers (TuJ-1, NF, MAP-2, NeuN). Although cell fusion phenomena with the host cells could not be ruled out, bone marrow-derived neurosphere transplantation could be a strategy for cellular mediated gene therapy.
Traumatic brain injury (TBI) is the leading cause of death and permanent disability in developmen... more Traumatic brain injury (TBI) is the leading cause of death and permanent disability in developmental age. Neurobehavioural symptoms are not uncommon in these patients. The aim of this study was to identify the main neuropsychiatric sequelae of TBI at different ages and study the possible correlations with clinical features in the acute phase and outcome in order to better plan rehabilitative treatment and re-entry into society. Ninety-six post-traumatic patients, ranging from 0-18 years, underwent a complete psychological evaluation protocol at I year from trauma. Patients were divided into three different age groups (0-6 years; 7-13 years; 14-18 years) and received a protocol made up of age-appropriate scales. Different psychological problems were found across the three groups; more frequently younger patients show internalizing problems such as withdrawal and closure, while, with age, behaviour problems become more frequent, characterized by hyperactivity and aggressiveness. Factors that were most predictive of psychological, behaviour and adjustment problems include GOS scores, the degree of impairment on the neurological examination and male gender. Psychological and behavioural problems differ across the three age groups and determine a different outcome, rehabilitation plan and re-entry into society. These problems should, thus, be investigated and treated specifically according to age.
Volume 1B: Extremity; Fluid Mechanics; Gait; Growth, Remodeling, and Repair; Heart Valves; Injury Biomechanics; Mechanotransduction and Sub-Cellular Biophysics; MultiScale Biotransport; Muscle, Tendon and Ligament; Musculoskeletal Devices; Multiscale Mechanics; Thermal Medicine; Ocular Biomechani..., Jun 26, 2013
Neuromuscular diseases as a consequence of brain damage are complex phenomena involving disuse, i... more Neuromuscular diseases as a consequence of brain damage are complex phenomena involving disuse, immobility, brain tissue remodeling and cortical function remapping. They may have various causes and strike any part of the population. The vicious circle leading to a worsening of the patients’ conditions proceeds through muscle shortening by contractures, disruption of the normal reflex behavior and sensory problems, development of spasticity [1]. Physical rehabilitation alone or in association with surgery or pharmacological treatments can be useful in limiting those degenerations. Besides manual rehabilitation, splints and braces are prescribed to control the limb posture and obtain stretching of the muscles. The role of those orthoses is to maintain the paretic limb in a set ‘physiological’ position and let it relax into that posture, in an attempt to reduce muscle rigidity and contractures. However applying a fixed constraint to the limb and waiting for relaxation to take place, may cause discomfort, pain, skin rash, and sundry different complications [2]. Also, any residual voluntary movement is prevented by a fixed-angle splinting. In addition, all these negative characteristics limit tolerability and daily application times. This work presents a different way to promote limb repositioning, based on the application of NiTi-alloy-based dynamic splints, which favor mobility and any residual use of the affected limb. Furthermore it suggests that application of mild contact forces prolonged in time has the advantage of feeling less painful and uncomfortable for the patients, improving overall treatment tolerability.
Persistent post-injury cognitive, academic and behavioural deficits have been documented in child... more Persistent post-injury cognitive, academic and behavioural deficits have been documented in children who sustained severe TBI during the school-age years. The major aim of this study was to examine and follow-up for 2 years the cognitive profile of a sample of post-injured patients (aged 6-16.11), in order to verify to what extent they recovered their intellectual functions after rehabilitation. Twenty-six patients who received a specific neuropsychological treatment and three cognitive evaluations with WISC-III were selected from a pool of 77. This group of patients showed a mild cognitive deficit at baseline, which improved over the 2 years to a borderline level. Despite the improvement in intellectual quotients and single sub-test scores achieved through rehabilitation, different recovery times were seen according to the function under study. The most common deficits are in processing speed, inferential and lexical-semantic skills. Detailed analysis of the WISC-III sub-tests allows for an accurate description of single cognitive functions after TBI. This allows one to make differential diagnoses between functional profiles and plan individualized rehabilitation treatments. Post-injured school-aged patients should receive rehabilitation for a period of at least 2 years, which is the time necessary for an at-least partial reorganization of basic cognitive functions.
SummaryBackground: Acquired brain injury (ABI) may result in lifelong impairment of physical, cog... more SummaryBackground: Acquired brain injury (ABI) may result in lifelong impairment of physical, cognitive, and psychosocial functions. Several rehabilitative treatments are often needed to support walking recovery, thus participants’ engagement becomes a crucial aspect, especially when patients are children. In the last few years, traditional physiotherapy (PT) has been flanked by innovative technologies for rehabilitation in the fields of robotics and Virtual Reality (VR). Preliminary results have shown interesting perspectives in the use of a VR system, the GRAIL (Gait Real-time Analysis Interactive Lab), in improving walking abilities in a small group of children with ABI, although further insights are needed about its use as rehabilitative tool in the pediatric population.Objectives: To evaluate the efficacy of a rehabilitation treatment on a GRAIL system for the improvement of walking abilities, in a group of children suffering from ABI.Methods: 12 children with ABI (study group – SG; mean age = 12.1 ± 3.8 years old) underwent a 10-session treatment with the GRAIL, an instrumented multi-sensor platform based on immersive VR for gait training and rehabilitation in engaging VR environments. Before (T0) and at the end of the treatment (T1), the participants were assessed by means of functional scales (Gross Motor Function Measure (GMFM), Functional Assessment Questionnaire (FAQ), 6-Minute Walk Test (6minWT) and the 3D-Gait Analysis, over ground (OGA) and on GRAIL (GGA).Results: All the participants completed the rehabilitative treatment. The functional evaluations showed an improvement in Gross Motor abilities (GMFM-88, p = 0.008), especially in standing (GMFM-D, p = 0.007) and walking (GMFM-E, p = 0.005), an increase of the endurance (6minWT, p = 0.002), and enhanced autonomy in daily life activities (FAQ, p = 0.025). OGA identified a significant decrease of the Gillette Gait Index for the impaired side and a general increase of symmetry. GGA showed improvements in spatiotemporal parameters and joints range of motion that moved towards normality and symmetry recovery.Conclusions: A 10-session treatment with GRAIL on children with ABI led to improvements in their walking abilities and enhanced their engagement during the training. This is desirable when long life impairments are faced and children’s motor functions have to be regained and it supports the leading role that VR might have in the rehabilitation field.
Prosthetics and Orthotics International, Sep 1, 2010
NiTi is a metal alloy with unconventional functional characteristics: Shape memory and pseudoelas... more NiTi is a metal alloy with unconventional functional characteristics: Shape memory and pseudoelasticity. Its use in the field of rehabilitation is very innovative. This work presents applications in lower limb orthotics. Three different devices were assembled and tested: An equinus gait dynamic splint, a compliant ankle positioning brace, and a dual-mode haptic/active exerciser for the dorsiflexors. Results are derived from technical and preclinical trials. The gait splint improves several walking parameters even better than a traditional flexible ankle-foot orthoses (AFO). In particular, it supports mid-stance and propulsion biomechanics and affects physiological activation of tibialis anterior during swing much less than posterior leaf AFO. The haptic/active exerciser, able to provide dorsiflexion through a suitable articular range, could be controlled on the basis of minimal surface electromyo-graphic (sEMG) signals, suggesting its use as an aid for early active workouts as soon as patients start to recover voluntary control of tibialis anterior. Further evidence must be sought in future to confirm for the ankle joint the promising results obtained in repositioning applications in prior upper limb studies. The work done so far on the tested prototypes is encouraging: Material characteristics and dimensioning will be optimized so that customized NiTi devices can be prescribed to best meet individual patients' requirements.
The Gait Real-time Analysis Interactive Lab (GRAIL) is an instrumented multi-sensor platform base... more The Gait Real-time Analysis Interactive Lab (GRAIL) is an instrumented multi-sensor platform based on immersive virtual reality for gait training and rehabilitation. Few studies have been included GRAIL to evaluate gait patterns in normal and disabled people and to improve gait in adults, while at our knowledge no evidence on its use for the rehabilitation of children is available. In this study, 4 children suffering from acquired brain injury (ABI) underwent a 5 session treatment with GRAIL, to improve walking and balance ability in engaging VR environments. The first and the last sessions were partially dedicated to gait evaluation. Results are promising: improvements were recorded at the ankle level, selectively at the affected side, and at the pelvic level, while small changes were measured at the hip and knee joints, which were already comparable to healthy subjects. All these changes also conveyed advances in the symmetry of the walking pattern. In the next future, a longer intervention will be proposed and more children will be enrolled to strongly prove the effectiveness of GRAIL in the rehabilitation of children with ABI.
Volume 1A: Abdominal Aortic Aneurysms; Active and Reactive Soft Matter; Atherosclerosis; BioFluid Mechanics; Education; Biotransport Phenomena; Bone, Joint and Spine Mechanics; Brain Injury; Cardiac Mechanics; Cardiovascular Devices, Fluids and Imaging; Cartilage and Disc Mechanics; Cell and Tiss..., 2013
ABSTRACT The ankle joint is a fundamental element in the biomechanical system of locomotion. When... more ABSTRACT The ankle joint is a fundamental element in the biomechanical system of locomotion. When its functions are impaired, due to neurological insult such as brain trauma or a stroke, severe disability and loss of personal independence may ensue. For this reason, great care is given to the physical rehabilitation of the lower limb. On the other hand, it is often the case that only a limited amount of time can be specifically devoted to the ankle joint manipulation during routine rehabilitation sessions. Furthermore, early initiation of active workout may be impossible for patients showing paresis; even passive exercise is often delivered to a minimal degree while the general conditions of the patients impose that they are kept bedridden. The delay in commencing rehabilitation may have negative consequences in terms of detrimental changes in tissue properties, deafferentation through lack of proprioceptive stimulation, learned non-use, and, ultimately, spastic paresis [1].
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Papers by Sandra Strazzer