Spinal cord injury (SCI) remains a significant cause for morbidity and mortality in North America. Bladder dysfunction following SCI is very common and could lead to severe complications including renal failure and autonomic dysreflexia (AD). AD involves life threatening episodes of hypertension in patients with SCI above T6 level. Current management protocols for AD are symptomatic and usually ineffective. Botulinum toxin-A (BTX-A), has been successfully used recently in SCI patients because it reduces the detrusor contractility via inhibiting acetylcholine release from efferent nerve endings. Recent evidence, however, suggests a sensory involvement via modulation of sensory neuropeptides, neurotransmitters, and receptors. It is still, however, unclear whether BTX-A can affect putative spinal neurons involved in AD. In this study we demonstrated that intravesical BTX-A treatment has blocked AD in rats with T4-SCI, and also provided a novel mechanism for the control of autonomic dysreflexia via a minimally invasive treatment modality.

Survival of transplanted neural stem/progenitor cells (NSPC) is limited after spinal cord injury (SCI). This thesis tested whether ephrin-B3 could enhance the survival of spinal cord derived NSPC because ephrin-B3 enhanced the survival of endogenous NSPC in the mouse brain. Preclustered ephrin-B3-Fc was tested, and preclustered Fc fragments and phosphate-buffered saline (PBS) were used as controls. This study showed that spinal cord derived NSPC and normal and injured rat spinal cord expressed EphA4 receptors. In culture, ephrin-B3-Fc increased the survival of NSPC at 1µg/mL (p<0.05), but Fc fragments reduced NSPC survival dose-dependently. In the injured spinal cord, infusion of ephrin-B3-Fc increased the proliferation of endogenous ependymal cells compared with infusion of PBS (p<0.05). However, in the injured cord, infusion of either ephrin-B3-Fc or Fc fragments caused a 20-fold reduction in the survival of transplanted NSPC (p<0.001). Thus, after SCI, ephrin-B3-Fc and Fc fragments are toxic to transplanted NSPC.

Spinal cord injury (SCI) remains a significant cause for morbidity and mortality in North America. Bladder dysfunction following SCI is very common and could lead to severe complications including renal failure and autonomic dysreflexia (AD). AD involves life threatening episodes of hypertension in patients with SCI above T6 level. Current management protocols for AD are symptomatic and usually ineffective. Botulinum toxin-A (BTX-A), has been successfully used recently in SCI patients because it reduces the detrusor contractility via inhibiting acetylcholine release from efferent nerve endings. Recent evidence, however, suggests a sensory involvement via modulation of sensory neuropeptides, neurotransmitters, and receptors. It is still, however, unclear whether BTX-A can affect putative spinal neurons involved in AD. In this study we demonstrated that intravesical BTX-A treatment has blocked AD in rats with T4-SCI, and also provided a novel mechanism for the control of autonomic dysreflexia via a minimally invasive treatment modality.

Survival of transplanted neural stem/progenitor cells (NSPC) is limited after spinal cord injury (SCI). This thesis tested whether ephrin-B3 could enhance the survival of spinal cord derived NSPC because ephrin-B3 enhanced the survival of endogenous NSPC in the mouse brain. Preclustered ephrin-B3-Fc was tested, and preclustered Fc fragments and phosphate-buffered saline (PBS) were used as controls. This study showed that spinal cord derived NSPC and normal and injured rat spinal cord expressed EphA4 receptors. In culture, ephrin-B3-Fc increased the survival of NSPC at 1µg/mL (p<0.05), but Fc fragments reduced NSPC survival dose-dependently. In the injured spinal cord, infusion of ephrin-B3-Fc increased the proliferation of endogenous ependymal cells compared with infusion of PBS (p<0.05). However, in the injured cord, infusion of either ephrin-B3-Fc or Fc fragments caused a 20-fold reduction in the survival of transplanted NSPC (p<0.001). Thus, after SCI, ephrin-B3-Fc and Fc fragments are toxic to transplanted NSPC.

Hand rehabilitation after injury or illness may allow a patient to regain full or at least partial use of a limb. However, rehabilitation often requires the patient to perform multiple repetitions of motions. While absolutely essential to regaining usage, such exercises are not always mentally engaging or enjoyable for the patient. The loss or degradation of the use of the hands can cause considerable loss of independence. In this dissertation, we present Mobile Music Touch (MMT), a wireless glove paired with a computing device, such as a laptop, smart phone, or MP3 player. The MMT system plays a song, while also "tapping" the fingers using vibration motors to indicate the correct finger to use to play the song on a piano keyboard. Learning a new skill or activity without active focus, an idea called Passive Haptic Learning(PHL) may allow an individual to learn one skill through their sense of touch while performing another, unrelated activity. Most rehabilitation activities are active in nature, requiring the focused participation of the injured person. Passive rehabilitation is the idea that some technologies and activities may bring about beneficial changes without the active engagement of the injured person. In order to study the concepts of PHL and PHR, we propose the Mobile Music Touch (MMT) system. We show that using passive rehabilitation in conjunction with the active rehabilitation of piano playing will bring about a greater degree of improvement in the hands than that achieved using only active rehabilitation. This dissertation research makes three unique contributions. First, we demonstrate that Passive Haptic Learning (PHL) using just the sense of touch is feasible and provides a form of learning and reinforcement of learned skills and tasks. Second, we identify the attributes and design features of a glove suited for long term wear by persons who use a manual wheelchair for mobility. Third, we show that Passive Haptic Rehabilitation (PHR) is possible using vibrotactile stimulation of the hands in persons classified as tetraplegic due to incomplete spinal cord injury.

Synucleins represent a conserved family of small proteins that include α-, β-, and γ- isoforms, which are highly expressed in neurons of the vertebrate nervous system. The normal function of these proteins is not well understood. However, in humans α- synuclein dysfunction is causatively linked to Parkinson’s Disease (PD), where it abnormally accumulates in neuronal cell bodies as protein aggregates that are associated with neuronal death. Although the associations between synuclein accumulation and cellular death are established in PD, the extent to which this occurs in other contexts, such as neuronal injury, is unknown. Furthermore, the effects of synuclein aggregation on the function of synapses, where synuclein is normally localized, are not well understood. To address these questions I took advantage of the experimentally accessible nervous system of the sea lamprey (Petromyzon marinus). I used molecular cloning and phylogenetic analyses to characterize three lamprey synuclein orthologues, one of which is highly expressed within a class of neurons called the giant reticulospinal (RS) neurons. Spinal cord injury induces the accumulation of synuclein protein only within a population of poor surviving RS neurons, and this accumulation is correlated with cellular death. Thus, similar to PD, the abundance of synuclein protein is associated with neuronal toxicity. In a related project, I demonstrated that elevating synuclein levels at synapses, such as occurs in PD, is deleterious to synaptic function through an inhibition of synaptic vesicle (SV) recycling. By injecting excess synuclein protein directly into the axons of giant RS neurons, and analyzing the ultrastructural morphology of synapses, I have shown that clathrin-mediated synaptic vesicle endocytosis was greatly inhibited. The conserved N-terminal domain was sufficient to inhibit vesicle recycling, and injecting synuclein mutants with disrupted N-terminal α-helices caused reduced defects in SV recycling. Therefore the α-helical structure of the N-terminus is necessary to inhibit SV recycling at early stages of clathrin-mediated endocytosis. Binding interactions with clathrin-mediated endocytosis components, such as the phosphoinositide lipid PI(4)P support this hypothesis. These studies provide a better understanding of the mechanisms by which synuclein dysfunction leads to neuronal death after injury and synaptic dysfunction in PD and other synuclein-associated diseases. / text

Spinal cord injury results in complete failure of the central neurons to regenerate and is associated with cyst formation and enlargement of the trauma zone. In contrast to the spinal cord, axons in the injured peripheral nerve have the capacity to undergo some spontaneous regeneration. However, significant post-traumatic loss of nervous tissue causing long nerve gap is one of the main reasons for the poor restoration of function following microsurgical repair of injured nerves. The present thesis investigates the effects of biodegradable conduits prepared from fibrin glue and poly-beta-hydroxybutyrate (PHB) in combination with cultured Schwann cells, mesenchymal stem cells and extracellular matrix molecules on regeneration after spinal cord and peripheral nerve injury in adult rats. At 4-8 weeks after transplantation into the injured spinal cord, the PHB conduit was well integrated into the cavity but regenerating axons were found mainly outside the PHB. When suspension of BrdU-labeled Schwann cells was added to the PHB, regenerating axons filled the conduit and became associated with the implanted cells. Modification of the PHB surface with extracellular matrix molecules significantly increased Schwann cell attachment and proliferation but did not alter axonal regeneration. To improve the labeling technique of the transplanted cells, the efficacy of fluorescent cell tracers Fast Blue, PKH26, Vibrant DiO and Cell Tracker™ Green CMFDA was evaluated. All tested dyes produced very efficient initial labeling of olfactory ensheathing glial cells in culture. The number of Fast Blue-labeled cells remained largely unchanged during the first 4 weeks whereas the number of cells labeled with other tracers was significantly reduced after 2 weeks. After transplantation into the spinal cord, Fast Blue-labeled glial cells survived for 8 weeks but demonstrated very limited migration from the injection sites. Additional immunostaining with glial and neuronal markers demonstrated transfer of the dye from the transplanted cells to the host tissue. In a sciatic nerve injury model, the extent of axonal regeneration through a 10mm gap bridged with tubular PHB conduit was compared with a fibrin glue conduit. At 2 weeks after injury, the fibrin conduit supported similar axonal regeneration and migration of the host Schwann cells compared with the PHB conduit augmented with a diluted fibrin matrix and GFP-labeled Schwann cells or mesenchymal stem cells. The long-term regenerative response was evaluated using retrograde neuronal labeling. The fibrin glue conduit promoted regeneration of 60% of sensory neurons and 52% of motoneurons when compared with the autologous nerve graft. The total number of myelinated axons in the distal nerve stump in the fibrin conduit group reached 86% of the nerve graft control and the weight of gastrocnemius and soleus muscles recovered to 82% and 89%, respectively. When a fibrin conduit was used to bridge a 20mm sciatic nerve gap, the weight of gastrocnemius muscle reached only 43% of the nerve graft control. The morphology of the muscle showed more chaotic appearance and the mean area and diameter of fast type fibers were significantly worse than those of the corresponding 10mm gap group. In contrast, both gap sizes treated with nerve graft showed similar fiber size. In summary, these results show that a PHB conduit promotes attachment, proliferation and survival of adult Schwann cells and supports marked axonal growth after transplantation into the injured spinal cord. The data suggest an advantage of the fibrin conduit for the important initial phase of peripheral nerve regeneration and demonstrate potential of the conduit to promote long-term neuronal regeneration and muscle recovery.

The level and completeness of spinal cord injury (SCI) above the first lumbar vertebra determine the degree of multi-system impairments including altered respiratory function and decreased capacity to maintain upright posture and seated postural stability in humans. Both systems were studied in able-bodied (AB) subjects and individuals with tetraplegia to explore the potential of functional electrical stimulation (FES) as a neuroprosthesis for seated postural control without compromising respiratory function. Data for AB participants (n=10) indicated higher tidal volumes, greater trunk extensor muscle activity, and different values of seated postural stability in upright sitting compared to slouch sitting. In three case studies of individuals with tetraplegia, surface FES was applied to trunk muscles. Changes in tidal volume, respiratory rate, and seated postural stability were case specific. These studies inform the development of a strategy for non-invasive FES as a neuroprosthesis for sitting balance while preserving respiratory function in individuals with SCI.

The level and completeness of spinal cord injury (SCI) above the first lumbar vertebra determine the degree of multi-system impairments including altered respiratory function and decreased capacity to maintain upright posture and seated postural stability in humans. Both systems were studied in able-bodied (AB) subjects and individuals with tetraplegia to explore the potential of functional electrical stimulation (FES) as a neuroprosthesis for seated postural control without compromising respiratory function. Data for AB participants (n=10) indicated higher tidal volumes, greater trunk extensor muscle activity, and different values of seated postural stability in upright sitting compared to slouch sitting. In three case studies of individuals with tetraplegia, surface FES was applied to trunk muscles. Changes in tidal volume, respiratory rate, and seated postural stability were case specific. These studies inform the development of a strategy for non-invasive FES as a neuroprosthesis for sitting balance while preserving respiratory function in individuals with SCI.

Tyrimo objektas – pacientų, patyrusių kaklinės dalies nugaros smegenų sužalojimą, ortostatinės reakcijos. Pacientų, patyrusių kaklinės dalies nugaros smegenų sužalojimą, ortostatinės reakcijos – viena didžiausių problemų, trukdanti siekti reabilitacijos programos tikslų. Reabilitacijos pradžioje, keičiant kūno padėtį, jiems dažnai svaigsta galva, pykina, gali net prarasti sąmonę. Visi šie simptomai neigiamai veikia pacientą, todėl svarbu šalinti ortostatinių reakcijų pasireiškimą vertikalizuojant kuo anksčiau. Darbo tikslas – nustatyti, kuris vertikalizavimo stovas – įprastas ar ERIGO – veiksmingiau mažina pacientų, patyrusių kaklinės dalies nugaros smegenų sužalojimą, ortostatines reakcijas. Uždaviniai: 1. Įvertinti tiriamųjų kraujospūdžio pokyčius vertikalizavimo metu su skirtingais stovais. 2. Įvertinti tiriamųjų širdies susitraukimo dažnio pokyčius vertikalizavimo metu su skirtingais stovais. 3. Įvertinti pacientų savijautą po vertikalizavimo su skirtingais stovais. 4. Nustatyti vertikalizavimo procedūros su skirtingais stovais toleruojamą trukmę. Hipotezė. ERIGO – vertikalizavimo stovas su mechanizmu pasyviems kojų judesiams – veiksmingiau mažina pacientų, patyrusių kaklinės dalies nugaros smegenų sužalojimą, ortostatines reakcijas. Tyrimo metodika. Tyrime dalyvavo 24 pacientai, kurie gydėsi Palangos reabilitacijos ligoninėje 2007–2008 metais po nugaros smegenų kaklinės dalies sužalojimo. Tiriamieji buvo suskirstyti į dvi grupes po 12 žmonių. Visiems pacientams buvo... [toliau žr. visą tekstą] / Study subject: Orthostatic reactions of the patients with cervical part spinal cord injuries. Orthostatic reactions for patients with cervical part spinal cord injuries is one of the most biggest problems, which disturbs to seek the aims of rehabilitation. Patients often suffer from dizziness, nausea and even might to lose consciousness at the beginning of the rehabilitation. All these symptoms has a negative impact to patients, so it must be reduced as soon as possible. Study aim: To determine which tilt-table- simple or Erigo-has the bigger effect for patient’s, wiht cervical part spinal cord injuries, orthostatic reactions. Study goals: 1. To evaluate the blood pressure changes of the patients during verticalization with different tilt-table; 2. To evaluate the heart rate changes of the patients during verticalization with different tilt-table; 3. To evaluate the state of the patients health after verticalization with different tilt-table; 4. To determine the tolerated duration of the virtualization procedure with different tilt-table. Hypothesis: Erigo - a tilt-table with passive legs movements – is more effective in reducing orthostatic reactions of the patients with cervical part spinal cord injuries. Study methods: The study included 24 patients with cervical part spinal cord injuries which had treatment at Palanga Hospital of Rehabilitation on 2007-2008 year period. Patients were divided in to two equal groups (12 patients in each group). All patients had the same... [to full text]