Restorative Neurology and Neuroscience - Volume 35, issue 6

Authors: Clarke, Darren | Penrose, Marissa A. | Penstone, Tamasin | Fuller-Carter, Paula I. | Hool, Livia C. | Harvey, Alan R. | Rodger, Jennifer | Bates, Kristyn A.

Article Type: Research Article

Abstract: Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that uses magnetic pulses over the cranium to induce electrical currents in underlying cortical tissue. Although rTMS has shown clinical utility for a number of neurological conditions, we have only limited understanding of how rTMS influences cellular function and cell-cell interactions. Objective: In this study, we sought to investigate whether repeated magnetic stimulation (rMS) can influence astrocyte biology in vitro . Method: We tested four different rMS frequencies and measured the calcium response in primary neonatal astrocyte cultures. We also tested the effect of rMS on …astrocyte migration and proliferation in vitro . We tested 3 to 4 culture replicates and 17 to 34 cells for each rMS frequency (sham, 1 Hz, cTBS, 10 Hz and biomemetic high frequency stimulation - BHFS). Results: Of all frequencies tested, 1 Hz stimulation resulted in a statistically significant rise in intracellular calcium in the cytoplasmic and nuclear compartments of the cultured astrocytes. This calcium rise did not affect migration or proliferation in the scratch assay, though astrocyte hypertrophy was reduced in response to 1 Hz rMS, 24 hours post scratch injury. Conclusion: Our results provide preliminary evidence that rMS can influence astrocyte physiology, indicating the potential for a novel mechanism by which rTMS can influence brain activity. Show more

Keywords: Astrocytes, repetitive transcranial magnetic stimulation, calcium signalling, injury

DOI: 10.3233/RNN-160708

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 557-569, 2017

Authors: Stepanichev, Mikhail | Onufriev, Mikhail | Aniol, Viktor | Freiman, Sofia | Brandstaetter, Hemma | Winter, Stefan | Lazareva, Natalia | Guekht, Alla | Gulyaeva, Natalia

Article Type: Research Article

Abstract: Background: Aging is associated with some cognitive decline and enhanced risk of development of neurodegenerative diseases. It is assumed that altered metabolism and functions of neurotrophin systems may underlie these age-related functional and structural modifications. CerebrolysinTM (CBL) is a neuropeptide mixture with neurotrophic effects, which is widely used for the treatment of stroke and traumatic brain injury patients. It is also evident that CBL has an overall beneficial effect and a favorable benefit-risk ratio in patients with dementia. However, the effects of CBL on cognition and brain neurotrophin system in normal aging remain obscure. Objective: The aim …of the present study was to examine the age-related modifications of endogenous neurotrophin systems in the brain of male Wistar rats and the effects of CBL on learning and memory as well as the levels neurotrophins and their receptors. Methods: Old (23–24 months) and young (2–3 months) male Wistar rats were used for the study. A half of animals were subjected to CBL course (2.5 ml/kg, 20 i.p. injections). Behavior of rats was studied using the open field test and simple water maze training. The contents of NGF and BDNF were studied using enzyme-linked immunosorbent assay; the expression of neurotrophin receptors was estimated by Western-blot analysis. Results: CBL treatment did not affect general status, age-related weight changes, general locomotor activity as well as general brain histology. In a water maze task, a minor effect of CBL was observed in old rats at the start of training and no effect on memory retention was found. Aging induced a decrease in neurotrophin receptors TrkA, TrkB, and p75NTR in the neocortex. CBL counteracted effects of aging on neocortical TrkA and p75NTR receptors and decreased expression of proNGF without influencing overall NGF levels. BDNF system was not significantly affected by CBL. Conclusion: The pro-neuroplastic “antiaging” effects of CBL in the neocortex of old animals were generally related to the NGF rather than the BDNF system. Show more

Keywords: Aging, brain, Cerebrolysin, neurotrophin, NGF, BDNF, TrkA, TrkB, p75NTR, neocortex, hippocampus, memory, rat

DOI: 10.3233/RNN-170724

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 571-581, 2017

Authors: Carelli, S. | Giallongo, T. | Gombalova, Z. | Merli, D. | Di Giulio, A.M. | Gorio, A.

Article Type: Research Article

Abstract: Background: Spinal cord injury (SCI) is a debilitating condition characterized by a complex of neurological dysfunctions ranging from loss of sensation to partial or complete limb paralysis. Recently, we reported that intravenous administration of neural precursors physiologically releasing erythropoietin (namely Er-NPCs) enhances functional recovery in animals following contusive spinal cord injury through the counteraction of secondary degeneration. Er-NPCs reached and accumulated at the lesion edges, where they survived throughout the prolonged period of observation and differentiated mostly into cholinergic neuron-like cells. Objective: The aim of this study was to investigate the potential reparative and regenerative properties of Er-NPCs …in a mouse experimental model of traumatic spinal cord injury. Methods and Results: We report that Er-NPCs favoured the preservation of axonal myelin and strongly promoted the regrowth across the lesion site of monoaminergic and chatecolaminergic fibers that reached the distal portions of the injured cord. The use of an anterograde tracer transported by the regenerating axons allowed us to assess the extent of such a process. We show that axonal fluoro-ruby labelling was practically absent in saline-treated mice, while it resulted very significant in Er-NPCs transplanted animals. Conclusion: Our study shows that Er-NPCs promoted recovery of function after spinal cord injury, and that this is accompanied by preservation of myelination and strong re-innervation of the distal cord. Thus, regenerated axons may have contributed to the enhanced recovery of function after SCI. Show more

Keywords: Spinal cord injury, neural stem cells, transplantation, regenerative medicine, animal behavior

DOI: 10.3233/RNN-170750

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 583-599, 2017

Authors: Rodseth, Jakob | Washabaugh, Edward P. | Krishnan, Chandramouli

Article Type: Research Article

Abstract: Background: Transcranial magnetic stimulation (TMS) is commonly used for assessing or modulating brain excitability. However, the credibility of TMS outcomes depends on accurate and reliable coil placement during stimulation. Navigated TMS systems can address this issue, but these systems are expensive for routine use in clinical and research environments. Objective: The purpose of this study was to provide a high-quality open source framework for navigated TMS and test its reliability and accuracy using standard TMS procedures. Methods: A navigated TMS system was created using a low-cost 3D camera system (OptiTrack Trio), which communicates with our free …and open source software environment programmed using the Unity 3D gaming engine. The environment is user friendly and has functions to allow for a variety of stimulation procedures (e.g., head and coil co-registration, multiple hotspot/grid tracking, intuitive matching, and data logging). The system was then validated using a static mockup of a TMS session. The clinical utility was also evaluated by assessing the repeatability and operator accuracy when collecting motor evoked potential (MEP) data from human subjects. Results: The system was highly reliable and improved coil placement accuracy (position error = 1.2 mm and orientation error = 0.3°) as well as the quality and consistency (ICC >0.95) of MEPs recorded during TMS. Conclusion: These results indicate that the proposed system is a viable tool for reliable coil placement during TMS procedures, and can improve accuracy in locating the coil over a desired hotspot both within and between sessions. Show more

Keywords: Frameless stereotaxic system, brain stimulation, neuronavigation, coil tracking, motor mapping, co-registration

DOI: 10.3233/RNN-170751

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 601-609, 2017

Authors: Thomas, Theresa Currier | Stockhausen, Ellen Magee | Law, L. Matthew | Khodadad, Aida | Lifshitz, Jonathan

Article Type: Research Article

Abstract: Background: As rehabilitation strategies advance as therapeutic interventions, the modality and onset of rehabilitation after traumatic brain injury (TBI) are critical to optimize treatment. Our laboratory has detected and characterized a late-onset, long-lasting sensory hypersensitivity to whisker stimulation in diffuse brain-injured rats; a deficit that is comparable to visual or auditory sensory hypersensitivity in humans with an acquired brain injury. Objective: We hypothesize that the modality and onset of rehabilitation therapies will differentially influence sensory hypersensitivity in response to the Whisker Nuisance Task (WNT) as well as WNT-induced corticosterone (CORT) stress response in diffuse brain-injured rats and shams. …Methods: After midline fluid percussion brain injury (FPI) or sham surgery, rats were assigned to one of four rehabilitative interventions: (1) whisker sensory deprivation during week one or (2) week two or (3) whisker stimulation during week one or (4) week two. At 28 days following FPI and sham procedures, sensory hypersensitivity was assessed using the WNT. Plasma CORT was evaluated immediately following the WNT (aggravated levels) and prior to the pre-determined endpoint 24 hours later (non-aggravated levels). Results: Deprivation therapy during week two elicited significantly greater sensory hypersensitivity to the WNT compared to week one (p  < 0.05), and aggravated CORT levels in FPI rats were significantly lower than sham levels. Stimulation therapy during week one resulted in low levels of sensory hypersensitivity to the WNT, similar to deprivation therapy and naïve controls, however, non-aggravated CORT levels in FPI rats were significantly higher than sham. Conclusion: These data indicate that modality and onset of sensory rehabilitation can differentially influence FPI and sham rats, having a lasting impact on behavioral and stress responses to the WNT, emphasizing the necessity for continued evaluation of modality and onset of rehabilitation after TBI. Show more

Keywords: Rehabilitation, physical therapy, diffuse traumatic brain injury, whisker barrel circuit, sensory sensitivity

DOI: 10.3233/RNN-170753

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 611-629, 2017

Authors: Turski, Christopher A. | Kessler-Jones, Alanna | Chow, Clara | Hermann, Bruce | Hsu, David | Jones, Jana | Seeger, Susanne K. | Chappell, Rick | Boly, Melanie | Ikonomidou, Chrysanthy

Article Type: Research Article

Abstract: Background: High definition transcranial direct current stimulation (HD-tDCS) has been administered over single brain regions for small numbers of sessions. Safety, feasibility and tolerability of HD-tDCS over multiple brain regions, multiple daily stimulations and long periods are not established. Objective: We studied safety, feasibility and tolerability of daily HD-tDCS over 2-4 brain regions for 20 sessions in healthy adults. Methods: Five healthy adults underwent physical and neurological examination, electrocardiogram (EKG), electroencephalogram (EEG) and cognitive screening (ImpACT) before, during and after HD-tDCS. Four networks (left/right temporoparietal and frontal) were stimulated in sequence (20 min each) using HD-tDCS in …20 daily sessions. Sessions 1–10 included sequential stimulation of both temporoparietal networks, sessions 11–15 stimulations of 4 networks and sessions 16–20 two daily stimulation cycles of 4 networks/cycle (1.5 mA/network). Side effects, ImpACT scores and EEG power spectrum were compared before and after HD-tDCS. Results: All subjects completed the trial. Adverse events were tingling, transient redness at the stimulation site, perception of continuing stimulation after end of session and one self-resolving headache. EEG power spectrum showed decreased delta power in frontal areas several days after HD-tDCS. While at the group level ImpACT scores did not differ before and after stimulations, we found a trend for correlation between decreased EEG delta power and individual improvements in ImpACT scores after HD-tDCS. Conclusion: Prolonged, repeat daily stimulation of multiple brain regions using HD-tDCS is feasible and safe in healthy adults. Preliminary EEG results suggest that HD-tDCS may induce long lasting changes in excitability in the brain. Show more

Keywords: HD-tDCS, tolerability, feasibility, safety, adverse events

DOI: 10.3233/RNN-170757

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 631-642, 2017

Authors: Thomas, Roger E. | Alves, Jorge | Vaska Mlis, Marcus M. | Magalhaes, Rosana

Article Type: Research Article

Abstract: Background: Assessment of therapies for the key consequences of mild traumatic brain injury (mTBI)/concussion is required. Objective: Identify all RCTs of mTBI/concussion therapy, risks of bias, and therapies with significant positive results. Methods: 17 electronic, 9 grey-literature databases searched without language/date restrictions; independent assessment of 1450 Abstracts/titles, 141 fulltext articles, 14 included RCTs. Results: Four RCTs used American Congress of Rehabilitation TBI definition, others used unique definitions. Risk of bias: 43% low risk randomization; 14% concealed assignments; 21% blinded participants/personnel; 57% blinded assessors; 64% low risk attrition; 100% no selective reporting. Eleven RCTs included …only mTBI. Ten significant positive results: six cognitive behavioral therapy (CBT), three videotape, pagers or personal digital assistants, and one physical therapy. One of referrals to health professionals no significant positive results. Three RCTs included both mTBI and moderate TBI. We wished to assess if authors proved using same interventions with both groups is appropriate. Two used CBT, one used pagers. All three RCTs significant positive results but results for their mild and moderate TBI patients were not separated. Two RCTs assessed return to work and no differences between intervention. Conclusion: Of 14 RCTs, six CBT, four digital assistants or videotape feedback and one physical therapy all had significant positive results. One referred patients to consultants and no significant positive results. Two assessed return to employment and no differences between interventions. Limitations are: (1) only four RCTs used the same concussion definition; (2) average age 38 (except for one study of adolescents, (3) all studies used unique interventions; (4) most authors used multiple interventions and effects could not be separated; (5) substantial attrition from eligibles to randomization, (4) only 64% at low risk from randomization, (5) 80 different outcome measures and meta-analysis was not possible, (6) only two studies assessed return to work. Show more

Keywords: Concussion, mild traumatic brain injury, evaluation, therapy, systematic review

DOI: 10.3233/RNN-170761

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 643-666, 2017

Authors: Dionello, Carla Fontoura | de Souza, Patrícia Lopes | Sá-Caputo, Danubia | Morel, Danielle Soares | Moreira-Marconi, Eloá | Paineiras-Domingos, Laisa Liane | Frederico, Eric Heleno Freire Ferreira | Guedes-Aguiar, Eliane | Paiva, Patricia de Castro | Taiar, Redha | Chiementin, Xavier | Marín, Pedro J. | Bernardo-Filho, Mario

Article Type: Research Article

Abstract: Background: The use of surface electromyography (sEMG) to evaluate muscle activation when executing whole body vibration exercises (WBVE) in studies provide neuromuscular findings, in healthy and diseased populations. Objectives: Perform a systematic review of the effects of WBVE by sEMG of lower limbs in non-healthy populations. Methods: The search using the defined keywords was performed in PubMed, PEDRo and EMBASE databases by three independent researchers. Applying the PRISMA statement several studies were selected according to eligibility criteria and organized for the review. Full papers were included if they described effects of WBVE for the treatment of …illnesses, evaluated by sEMG of lower limbs independently on the year of the publication; in comparison or associated with other treatment and evaluation techniques. Results: Seven publications were selected; two in spinal cord injury patients, one in Friedreich’s ataxia patients, three in stroke patients and one study in breast cancer survivors. Reported effects of WBV in were muscle activation by sEMG and also on strength, blood flow and exercise resistance; even in paretic limbs. Conclusion: By the use of sEMG it was verified that WBVE elicits muscle activation in diseased population. These results may lead to the definition of exercise protocols to maintain or increase muscular activation. However, due to the heterogeneity of methods among studies, there is currently no consensus on the sEMG signal processing. These strategies might also induce effects on muscle strength, balance and flexibility in these and other illnesses. Show more

Keywords: Electromyography, muscle, whole body vibration, rehabilitation

DOI: 10.3233/RNN-170765

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 667-681, 2017

Authors: Kodama, Takayuki | Nakano, Hideki | Katayama, Osamu | Murata, Shin

Article Type: Research Article

Abstract: Background: The association between motor imagery ability and brain neural activity that leads to the manifestation of a motor illusion remains unclear. Objective: In this study, we examined the association between the ability to generate motor imagery and brain neural activity leading to the induction of a motor illusion by vibratory stimulation. Methods: The sample consisted of 20 healthy individuals who did not have movement or sensory disorders. We measured the time between the starting and ending points of a motor illusion (the time to illusion induction, TII) and performed electroencephalography (EEG). We conducted a temporo-spatial …analysis on brain activity leading to the induction of motor illusions using the EEG microstate segmentation method. Additionally, we assessed the ability to generate motor imagery using the Japanese version of the Movement Imagery Questionnaire-Revised (JMIQ-R) prior to performing the task and examined the associations among brain neural activity levels as identified by microstate segmentation method, TII, and the JMIQ-R scores. Results: The results showed four typical microstates during TII and significantly higher neural activity in the ventrolateral prefrontal cortex, primary sensorimotor area, supplementary motor area (SMA), and inferior parietal lobule (IPL). Moreover, there were significant negative correlations between the neural activity of the primary motor cortex (MI), SMA, IPL, and TII, and a significant positive correlation between the neural activity of the SMA and the JMIQ-R scores. Conclusion: These findings suggest the possibility that a neural network primarily comprised of the neural activity of SMA and M1, which are involved in generating motor imagery, may be the neural basis for inducing motor illusions. This may aid in creating a new approach to neurorehabilitation that enables a more robust reorganization of the neural base for patients with brain dysfunction with a motor function disorder. Show more

Keywords: Motor illusion, microstate segmentation method, supplementary motor area, JMIQ-R

DOI: 10.3233/RNN-170771

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 683-692, 2017

Authors: Heese, Klaus

Article Type: Research Article

Abstract: In an aging society with dementia imposing an increasing threat to higher brain cognitive functions, understanding the molecular and cellular events of adult neurogenesis is imperative. Interleukin-6 (IL-6), along with its agonistic acting soluble receptor sIL-6R (the combined proteins are also known as Hyper-IL-6), is a promising cytokine that can support neurogenesis under conditions of neurodegeneration when neuron replacement is needed. In contrast to the previously reported gliogenic effects of activation of the IL-6–signal transducer and activator of transcription 3 (STAT3) axis, this review summarizes recent studies showing that IL-6 activation can be neurogenic and has potential therapeutic applications for …the treatment of neurodegenerative diseases such as Parkinson’s disease. Show more

Keywords: Brain, IL-6, neural stem cell, neurogenesis, neuron, signaling, synapse

DOI: 10.3233/RNN-170772

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 693-701, 2017