bluuebunny/crossref_metadata_2025 huggingface dataset:
Symptomatic treatment of unresponsive wakefulness syndrome with transcranially focused extracorporeal shock waves
Authors: Lohse-Busch H. , Reime U. , Falland R.
Published: December 2019

Objective:

Can stimulation of nerve growth factors by focused transcranial extracorporeal shock wave therapy (TESWT) be made effective for persons within unresponsive wakefulness syndrome (apallic syndrome)?

Design:

Between eight and 18 years after the brain lesion, five patients with unresponsive wakefulness syndrome of differing severity received TESWT with the device Duolith (Storz Medical) during four-week physicomedical complex therapies. In the previous years they had been treated with the same complex therapies without TESWT. The vigilance did not change.

Results:

After two-four years and an average of 5.2 treatment series, the patients' abilities improved by 135.9% on the German Coma Remission Scale (KRS) and by 43.6% on the Glasgow Coma Scale. In the motor area of the KRS, the patients improved by 64.3%. Three PEG feeding tubes could be removed, nonverbal communication initiated four times.

Conclusion:

In this longitudinal observation study, focused TESWT stimulated vigilance in patients with unresponsive wakefulness syndrome. The precise neurophysiological effects remain to be verified by a study of the clinical results.
The impact of high intensity physical training on motor and non-motor symptoms in patients with Parkinson's disease (PIP): A preliminary study
Authors: Morberg Bo M. , Jensen Joakim , Bode Matthias , Wermuth Lene
Published: December 2019

Background:

Parkinson's disease (PD) is a neurodegenerative disease caused by loss of dopaminergic nigrostriatal neurons. Several studies have investigated various physical interventions on PD. The effects of a high intensity exercise program with focus on resistance; cardio; equilibrium; and flexibility training have not been evaluated previously.

Objective:

The aim of this study was to investigate the effects of a complex, high intensity physical training program, with a long duration, on motor and non-motor symptoms in patients with PD.

Method:

24 patients with PD Hoehn and Yahr stage 1–3 were non-randomly allocated to an intervention group (n = 12) and a control group (n = 12). The intervention group underwent 32 weeks of high intensity personalized physical training twice a week, with an optional extra training session once a week. The control group received general recommendations regarding physical activity. The primary outcomes were the change in Unified Parkinson's Disease Rating Scale Subscores (UPDRS) and the Parkinson's Disease Questionnaire (PDQ-39).

Results:

At week 32, the training significantly improved both UPDRS motor subscores (p = 0.045), activities of daily living subscores (ADL) (p = 0.006), mentation subscores (p = 0.004) and complication subscores (p = 0.019). The effect on the PDQ39 total score was not statistically significant. The intervention group however experienced a substantial improvement of the PDQ39 items emotional well-being (−11.0) and bodily discomfort (−7.14).

Conclusion:

The results suggest that a personal high intensity exercise program may favorably influence both motor and non-motor symptoms in patients with mild to moderate PD. More studies with both higher methodology in study design and a follow-up examination are recommended.
Transcallosal fibers from corticospinal tract in patients with cerebral infarct
Authors: Jang Sung Ho , Park Kyung-A , Ahn Sang Ho , Cho Yoon Woo , Byun Woo Mok , Son Su Min , Choi Jin Ho , Kwon Young Hyun
Published: December 2019

Diffusion tensor image tractography (DTT) can visualize white matter tracts and provide a powerful vehicle with which to investigate the neural pathway at the subcortical level. We attempted to demonstrate the clinical significance of transcallosal fibers (TCF) originating from the corticospinal tract in patients with corona radiata infarct located below the corpus callosum, using diffusion tensor image tractography (DTT). Forty patients with corona radiata infarct located below the corpus callosum and 26 control subjects were enrolled in this study. We classified the DTT findings as follows: no transcallosal fiber from the CST (type A), transcallosal fiber ended in the corpus callosum or connected to the cortex of the opposite hemisphere (type B), and transcallosal fiber that descended toward the lesion after passing through the corpus callosum (type C). Type C indicated that the presence of transcallosal fibers starting from the CST of the unaffected hemisphere was significantly more prevalent in the patients, and these patients showed the poorest motor function. It seems that transcallosal fibers originated from the CST of the unaffected hemisphere, and fibers descending toward the lesion in patients with corona radiata infarct may act to compensate for motor deficits.
FES-propelled cycling of SCI subjects with highly spastic leg musculature
Authors: Szecsi J. , Schiller M.
Published: December 2019

Background:

The presence of spasms precludes the use of artificial electrical activation of the muscles to restore mobility. The prospect of using an electrical stimulus that produces motor activation without causing unwanted reflex activation in patients with high levels of spasticity is an appealing one.

Objective:

The purpose of the study was to determine the efficacy of modulated middle frequency alternating current (MFAC) muscle stimulation compared to the conventional method of standard low frequency rectangular pulse (LFRP) stimulation used in cycling of persons with spinal cord injury (SCI) and pronounced spasticity.

Methods:

To evaluate cycling-relevant differences between stimulation modes, 13 subjects with SCI (ASIA-A), 11 of them with strong spasticity, underwent isometric and cycling measurements using both 20 Hz LFRP and 4 KHz modulated with 50 Hz MFAC. The isometric long-lasting reflex torque response in the quadriceps and hamstrings muscles, and the dynamic work during 1000 sec of ergometric cycling as well as the number of involuntary stops caused by hyperreflexia were recorded.

Results:

The long-lasting reflex torque response was significantly lower when using MFAC than with LFRP stimulation. During MFAC stimulation work generated was on average 374% higher ( p = 0.002) and the number of involuntary stops was on average 32% lower ( p < 0.001) than during standard LFRP stimulation-propelled cycling.

Conclusion:

These findings suggest that MFAC-stimulated cycling of strongly spastic SCI subjects is more effective in terms of generated isometric torque and power than stimulation with LFRP. Thus, more health benefits, e.g., cardiovascular and muscular training and spasticity-decreasing effects, can be expected faster using MFAC instead of LFRP in stimulation-propelled cycling.
Assessing the reliability of the Modified Modified Ashworth Scale between two physiotherapists in adult patients with hemiplegia
Authors: Ansari Noureddin Nakhostin , Naghdi Soofia , Hasson Scott , Fakhari Zahra , Mashayekhi Masoud , Herasi Mona
Published: December 2019

The Modified Modified Ashworth Scale (MMAS) is a simple clinical outcome measure to assess muscle spasticity in people with brain injury. The objective of this cross-sectional study was to assess the interrater reliability of the MMAS in the upper limb of adult patients with hemiplegia. Participants were fifteen patients with a mean age of 57.3 ± 14.4 years. They had brain injury on average 33.3 ± 26.2 months earlier. Two common spastic muscle groups (elbow flexor and wrist flexor) on the hemiparetic side of the patients were rated by two physiotherapists according to a standardized protocol. The order of raters' assessment and the sequence of muscle testing was randomized. The weighted Kappa (κw) values were calculated for reliability. The κw was 0.61 for elbow flexor and 0.78 for wrist flexor. Results support the good interrater reliability of the MMAS for persons with upper limb spasticity.
Cortical activation pattern of compensatory movement in stroke patients
Authors: Lee Mi Young , Park Ji Won , Park Rae Joon , Hong Ji Heon , Son Su Min , Ahn Sang Ho , Cho Yoon Woo , Jang Sung Ho
Published: December 2019

Objective:

Little is known about the cortical activation pattern of compensatory movement (CM) in stroke patients. We attempted to investigate the cortical activation pattern of compensatory movement in stroke patients, using functional MRI (fMRI).

Methods:

Eight hemiparetic stroke patients were recruited for this study. We measured the shoulder abduction angle when each subject was simulating eating in a sitting position, which was considered as the degree of CM. The fMRI was performed at 1.5T using an elbow motor task at a frequency of 0.5 Hz.

Results:

There was an inverse correlation between the shoulder abduction angle of the affected side and the LI (Laterality Index) ( r = −0.745; p < 0.05). The shoulder abduction angle of the affected side was significantly related to the sum of activated voxels in all regions of interest ( r = 0.776; p < 0.05) and the activated voxels of the supplementary motor area ( r = 951; p < 0.05). However, we did not find any correlation between the shoulder abduction angle and the activated voxels of other brain areas.

Conclusions:

We demonstrated that a greater shoulder abduction angle on the affected side requires more cortical activation. Therefore, CM appears to be related to the change of the cortical motor control toward greater recruitment of cortical neurons.
Effect of motor imagery training on symmetrical use of knee extensors during sit-to-stand and stand-to-sit tasks in post-stroke hemiparesis
Authors: Oh Duck-Won , Kim Jin-Seop , Kim Suhn-Yeop , Yoo Eun-Young , Jeon Hye-Seon
Published: December 2019

Objective:

To investigate the effect of motor imagery training (MIT) on the symmetrical use of knee extensors during sit-to-stand and stand-to-sit tasks.

Methods:

We measured the electromyographic (EMG) data in the knee extensor on the affected side of 3 volunteers with post-stroke hemiparesis. We used a single-subject multiple-baseline research design across individuals. The EMG data were collected from knee extensors while performing the sit-to-stand and stand-to-sit tasks. The EMG activation and onset time ratios for the knee extensors were calculated by dividing the EMG activation and onset time of knee extensor action on the affected side by these on the unaffected side. MIT consisted of a 10-min detailed description of 5 stages: preparation, sit-to-stand tasks, weight shifting during standing, stand-to-sit tasks, and completion.

Results:

During MIT, the EMG activation ratios of participants 1, 2, and 3 increased by 11.24%, 18.07%, and 26.91%, respectively, in the sit-to-stand task and by 12.11%, 14.31%, and 25.92%, respectively, in the stand-to-sit task. During MIT, the onset time of participants 1, 2, and 3 decreased by 36.09%, 24.27%, and 25.61%, respectively, in the sit-to-stand task and by 26.81%, 27.20%, and 22.83%, respectively, for the stand-to-sit task.

Conclusion:

These findings suggest that MIT has a positive effect on the symmetrical use of knee extensors during sit-to-stand and stand-to-sit tasks.
The cortical activation effect of phonation on a motor task: A functional MRI study
Authors: Lee Mi Young , Kwon Yong Hyun , Park Ji Won , Choi Jin Ho , Son Su Min , Ahn Sang Ho , Cho Yoon Woo , Jang Sung Ho
Published: December 2019

It is well-known that sound production can affect the motor system. We investigated whether a short, loud phonation affected cortical activation caused by a motor task using functional MRI. Fifteen right-handed healthy subjects were recruited for this study. We compared the cortical activation caused by the performance of a motor task (right hand grasp-release movements) to that caused by the performance of the motor task with phonation(“ah” sound). We found that performance of the motor task with phonation resulted in less activation in the primary sensori-motor cortex than did the performance of the motor task alone. It seemed that phonation during the motor task enhanced the efficiency of cortical activation compared to that caused by the motor task alone.
Endurance exercise training promotes angiogenesis in the brain of chronic/progressive mouse model of Parkinson's Disease
Authors: Al-Jarrah Muhammed , Jamous Mohammad , Al Zailaey Khalid , Bweir Salameh O.
Published: December 2019

Goals and objectives:

The main goal of this study is to evaluate the effect of treadmill exercise on the angiogenesis markers in the striatum (ST) of chronic/progressive parkinsonian mice.

Materials and Methods:

Forty 57BL/6 albino mice were randomly divided into four groups. Sedentary control (SC, n = 10), exercise control (ExC, n = 10), sedentary Parkinson’s (SPD, n = 10), and exercised Parkinson’s (ExPD, n = 10). Parkinsonism was induced by the injection with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks, three days and half a part. Following the induction of parkinsonism, ExPD and ExC animal groups were trained on a modified human treadmill at a speed of 18 m/min, 0° of inclination, 40 min/day, 5 days/week for 4 weeks. The remaining two groups (SPD and SC) were housed in cages for the same period. At the end of the experiment, the angiogenesis markers; Vascular Endothelial Growth Factor (VEGF) and CD34 were examined in the striatum in the four animal groups.

Results:

PD resulted in a significant decrease in blood vessel density with the comparison between the sedentary control and PD model animals ( p < 0.005). Four weeks of treadmill exercise training significantly increased angiogenesis in the striatum in ExPD groups ( p < 0.05). Exercise also induced an increase in blood vessel density in the striatum of the control animals, but the change was not significant ( P < 0.3).

Conclusion:

These data suggest that 4 weeks of treadmill exercise promoted angiogenesis in the brain of chronic Parkinsonian mice, which can partially explain the beneficial role exercise in patients with PD. Further studies are required to determine the mechanism of exercise-induced angiogenesis in PD.
Assessment and treatment of common persistent sequelae following blast induced mild traumatic brain injury
Authors: Schultz Billie A. , Cifu David X. , McNamee Shane , Nichols Michelle , Carne William
Published: December 2019

The ongoing wars in Iraq and Afghanistan and terrorist activity worldwide have been associated with an increased incidence of blast injuries. While blast injuries share similarities with blunt or penetrating traumatic injuries, there are unique mechanistic elements of blast injury that create increased vulnerability to damage of specific organs. This review highlights the mechanism of blast-related injury, describes the common sequelae of blast exposure that may impact rehabilitation care, and summarizes the intervention strategies for these blast-related sequelae.
Parental stress and marital relationships among patients with brain injury and their spouses
Authors: Kieffer-Kristensen R. , Teasdale T.W.
Published: December 2019

Introduction/Objectives:

This study examines parental stress and marital relationship among patients with acquired brain injury and their spouses.

Participants, Materials/Methods:

The participants were 35 patients diagnosed with acquired brain injury and having school-aged children, together with their spouses recruited from out-patients from brain injury rehabilitation units across Denmark. The parents self-reported parental stress using the Parental Stress Index (PSI), marital adjustment using the Dyadic Adjustment Scale (DAS), family functioning using the Family Environment Scale (FES). Additionally, the healthy parents completed the Symptom Checklist 90 (SCL-90) measuring psychological symptoms. A matched control group consisted of parents suffering from diabetes and their spouses, being recruited from the National Danish Diabetes Register.

Results:

Significantly more symptoms of parental stress were reported by the brain-injured parents when compared to the diabetic parents ( p < 0.05); the brain injured parents also reported significant more family dysfunction ( p < 0.05). The healthy parents in the brain injury group rated their marital satisfaction and current relationship happiness significantly lower ( p < 0.05) than the healthy control group. The spouses to the brain-injured patients were also significantly more depressed ( p < 0.01).

Conclusions:

When parents have acquired brain injury, they experience more parental stress and family dysfunction. Their spouses are less satisfied in their marital relationship and feel more depressed. These results indicate the need of a family centred supportive service to focus on the relational changes and dysfunctional family processes in families with a brain-injured parent and dependent children.
Substance use among persons with traumatic brain injury: A review
Authors: West Steven L.
Published: December 2019

This paper provides a review of the current literature in the area of substance use and traumatic brain injury (TBI). Collectively, these studies demonstrate that substance use and SUD are common in the TBI population both pre- and post-injury, are a frequent causative factor in injury acquisition, complicate the rehabilitation process, and have substantial negative impact on individual health and well being. Further, individuals with a demonstrated SUD and concurrent TBI are likely to be severely limited in their ability to access SUD care due to physical barriers. This literature is reviewed and then considered in terms of its general weaknesses. Finally, a brief outline of future research needs is provided.
The effect of combining daily restraint with bimanual intensive therapy in children with hemiparetic cerebral palsy: A self-control study
Authors: Cohen-Holzer Marilyn , Katz-Leurer Michal , Reinstein Rachel , Rotem Hemda , Meyer Shirley
Published: December 2019

Aim:

To examine the influence of combining restraint therapy with bimanual intensive therapy on the unimanual and bimanual function among children with hemiparetic cerebral palsy (CP). Included were nine children (ages 6–9 yr), with Manual Ability Classification System scores of 2–3, Gross Motor Functional Classification System 1–2; Intervention: 10 days, six hours per day including one hour of restraint followed by five hours of bimanual activities.

Evaluations:

One month and immediately prior to the intervention (as the control period), immediately, two months and six months post-intervention. The Assisting Hand Assessment was the primary outcome measure, along with the Jebsen-Taylor Test of Hand Function, the Jamar pinch gauge for grip and pinch, and the Pediatric Evaluation of Disability Inventory (PEDI).

Results:

No significant change was observed during the pre-intervention control period in any of the outcome measures; a significant improvement in all outcome parameters was noted after the intervention as compared to the control period. These achievements were still significantly higher than baseline values at six months post-intervention.

Conclusion:

Children with hemiparetic CP at this level of impairment might benefit from a short daily intervention program of combining restraint with bimanual training in order to improve unimanual and bimanual function.
Effects of levodopa on forward and backward gait patterns in persons with Parkinson's disease
Authors: Bryant M.S. , Rintala D.H. , Hou J.G. , Lai E.C. , Protas E.J.
Published: December 2019

Introduction:

Backward walking is difficult for persons with Parkinson’s disease (PD). It is unknown how levodopa influences backward gait patterns, especially when compared to forward gait patterns.

Purpose:

Investigate the effects of levodopa on forward and backward gait patterns in individuals with PD.

Design:

A repeated measures design was used.

Methods:

The sample consisted of 21 individuals with PD (15 males, 6 females). Their mean age was 70.24 ± 8.69 yr. The average time since diagnosis was 11.81 ± 5.49 years. The median of the Hoehn and Yahr stage while ‘ON’ medication was 2.57. Gait patterns during forward and backward walking at a self-selected comfortable speed were recorded before and after taking levodopa on the same day.

Results:

Levodopa significantly increased gait speed and stride length and decreased the percent of the gait cycle (%GC) spent in double support. Gait speed and stride length were greater and the %GC spent in double support was less during forward walking compared with backward walking. Cadence was not changed by levodopa or walking direction.

Conclusions:

Levodopa improved gait characteristics during backward walking in a manner similar to that during forward walking in persons with PD.
Cortical reorganization of hand motor function to face somatotopy in a patient with brain injury: A functional MRI study
Authors: Kwon Hyeok Gyu , Kim Oh Lyong , Kim Seong Ho , Lee Dong Gyu , Byun Woo Mok , Jang Sung Ho
Published: December 2019

We report on a patient with a meningioma whose hand motor function appeared to be reorganized mainly into the face somatotopy of the primary motor cortex (M1) following meningioma removal, using functional RMI (fMRI). A 76-year-old right-handed woman showed leukomalactic lesions in the left fronto-parietal lobes and subcortical white matter, including the upper portion of the precentral knob after meningioma removal. She recovered motor function to the point that she was able to extend the affected fingers against gravity at 6 weeks and extend the affected fingers against resistance at 12 weeks. The right primary sensori-motor cortex centered on the precentral knob was activated during movement of the unaffected (left) hand. By contrast, the face somatotopy and inferior portion of the precentral knob of the left primary motor cortex were activated during movement of the right hand. Peak activations were present at the left face somatotopy of the primary motor cortex during movement of the right hand and the right precentral knob during movement of the left hand. Motor function of the affected hand appeared to be reorganized mainly into the face somatotopy of the primary motor cortex and partially into the lower portion of the precentral knob after meningioma removal.
Effects of forced use combined with scheduled home exercise program on upper extremity functioning in individuals with hemiparesis
Authors: Park Hae-Yean , Yoo Eun-Young , Park Soo Hyun , Park Ji-Hyuk , Kang Dae-Hyuk , Chung Bo-In , Jung Min-Ye
Published: December 2019

Objectives:

The aims of this study were to 1) investigate the effects of forced use combined with scheduled home exercise program compared to forced use only on increasing upper extremity functioning, 2) examine whether increased upper extremity functioning generalized to activities of daily living (ADL) functioning, and 3) explore participants’ psychosocial functioning.

Methods:

A single-subject A-B-A’-C research design was employed in this study. The intervention consisted of two conditions: forced use only (intervention period B), and forced use in addtion to scheduled home exercise program (intervention period C).

Results:

The results were as follows: 1) Forced use combined with scheduled home exercise program compared to forced use only allowed individuals with stroke to take part in exercise programs on their own within their home setting, ultimately improving their upper extremity functioning. 2) The program’s promotion of performance in ADL tasks have the advantage of keeping participants focused so that a number of exercises can be maintained throughout the intervention. 3) Finally, forced use combined with scheduled home exercise program showed partial effects on improving the participants’ psychosocial functioning.

Conclusion:

The results of the present study suggest that forced use combined with scheduled home exercise program compared to forced use only has the potential to be a cost- and resource-efficient method for intensifying rehabilitation.
A RFID-based anomaly detection approach for material supply of mixed-product assembly
Authors: Cao Xiaohua , Li Qingxia , Miller Olivia
Published: December 2019

In a mixed-product assembly line, material supply is very complicated, dynamically changing and error-prone due to large material flow. These uncertainties often cause some imperceptible Abnormal Logistics States (ALSs), which seriously hinder accurate and efficient delivery of materials to the assembly lines. There is no relevant theoretical model and efficient information collection technology so far. This paper aims to detect those imperceptible abnormal logistics states in mixed-product assembly lines through a novel RFID-based multi-deviation detection approach. Some ALSs' parameters are defined from different perspectives such as time, location, number, sequence and path. A calculation model of ALSs has been built by processing RFID data, then a RFID-based multi-deviation model is presented to quantify the abnormal degree of ALSs. Based on the developed models, a judging algorithm for ALSs of material supply is proposed. Compared to conventional eKanban monitor system, the proposed approach can detect the ALSs of material supply efficiently and accurately, including those that are difficult to detect in eKanban monitor system.
A traceable platform of aquatic foods supply chain based on RFID and EPC Internet of Things
Authors: Yan Bo , Hu Die , Shi Ping
Published: December 2019

This paper designs and develops a traceable platform of aquatic foods supply chain based on Radio Frequency Identification (RFID) and Electronic Product Code (EPC) Internet of Things, and focuses on designing Object Name Service (ONS) and EPC Information Service (EPCIS) of this platform. Tracking, traceability, recall and monitoring of tilapia products in the food supply chain can be achieved with participation of consumers, enterprises and the government. This platform contains aquaculture management system, process management system, distribution management system, sales management system, and querying and monitoring system, and realizes all-the-way traceability of aquatic products from breeding, processing, distribution to sales.
Challenges for building RFID tracking systems across the whole supply chain
Authors: Hinkka Ville
Published: December 2019

Even though numerous articles and real life cases have highlighted the benefits of radio frequency identification (RFID) tracking for supply chain management for almost a decade, companies are rather slow to implement the technology. This paper concentrates on researching the reasons for the slow adoption of RFID tracking in the supply chain management using literature review and multiple case studies as the research methodology. The literature review of the articles classifies different challenges for RFID tracking implementation and elicits the academic explanations for the slow acceptance of the technology. The conclusion of the literature review is that most of the published articles have been concentrating on presenting technological obstacles to RFID tracking implementation, while the problems nowadays are increasingly organizational or inter-organizational. Also companies usually settle for using RFID tracking to improve their operational processes instead of exploiting the full potential in the technology and the increased visibility for improving managerial processes of the company, or upgrading the efficiency of the whole supply chain. In addition to the literature review, five RFID tracking case surveys are presented to provide experience and insights into managerial decisions concerning supply chain-wide RFID tracking solutions. Followed by the literature review and case studies, this paper presents a framework, which suggests three levels, where different potential challenges to supply chain-wide RFID tracking system implementations should be handled: the supply chain, inside a company or inside a certain function.
Modeling early Parkinson's disease pathology with chronic low dose MPTP treatment
Authors: Korecka Joanna A. , Eggers Ruben , Swaab Dick F. , Bossers Koen , Verhaagen Joost
Published: December 2019

Purpose: Parkinson's disease (PD) is a movement disorder mainly characterized by progressive neurodegeneration of dopaminergic (DAergic) neurons in the substantia nigra (SN). As yet, unknown molecular changes contribute to the development of PD leading to a great need for in vivo models that herald this disorder. Here we characterize an animal model presenting early PD pathology. Methods: Young, adult C57/BL6 mice were treated for five weeks twice a week with 15 mg/kg 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) in combination with 250 mg/kg probenecid. During the treatment mice were tested on their dopamine dependent movement skills. The integrity of their nigrostriatal system was examined through immunohistochemical studies. Results: During the treatment, mice developed dopamine-dependent movement deficits induced by loss of tyrosine hydroxylase (TH) positive nigrostriatal axon terminals. Immunohistochemical study identified astrogliosis and microgliosis in the SN but no decrease of TH immunostaining, demonstrating lack of DAergic neuron degeneration. We also observed formation of α-synuclein inclusion bodies in the SN. Conclusions: The combined features of this MPTP model appear to represent an early neurotoxic cellular stress to the SN neurons bearing a striking resemblance to the early stages of PD neuropathology. This model might prove very useful to investigate early neurodegenerative events in the nigrostriatal DAergic system and to study the effects of potential treatment strategies counteracting the early PD cellular changes.
Neuroprotective effects of SNX-185 in an In Vitro model of TBI with a second insult
Authors: Shahlaie Kiarash , Gurkoff Gene G. , Lyeth Bruce G. , Muizelaar J. Paul , Berman Robert F.
Published: December 2019

Purpose: Second insults following traumatic brain injury (TBI), such as ischemia and hypoxia, significantly worsen outcome in patients and in experimental models of TBI. Following TBI there is a pathological increase in intracellular calcium, triggering cellular mechanisms of dysfunction and death. N-type specific voltage gated calcium channel (VGCC) blockers reduce cell death in both in vitro mechanical strain injury (MSI) and in vivo models of TBI, but they have not been previously explored in a model of TBI followed by a second insult. Methods: In the following studies, cortical neurons and astrocytes experienced MSI followed by incubation in 20% CO2. Cultures were treated with the N-type VGCC blocker, ω-conopeptide SNX-185 (1 μM), 5-minutes post-injury and intracellular calcium accumulation was assessed at 3, 6 and 24 h. Neuronal viability was assessed 24 h after MSI. Results: Increasing incubator CO2 to 20% significantly increased calcium accumulation and cell death regardless of MSI severity. Treatment with 1 μM of SNX-185 significantly reduced the accumulation of calcium 3 hours following injury and increased the number of viable neurons 24 h post-injury and incubation in 20% CO2. Conclusions: In vitro models provide a critical tool for identifying roles of cell specific mechanisms involved in neuronal dysfunction and death following injury. These data demonstrate the potential of N-type VGCC blockers in reducing the damaging effects of TBI and second insults.
Epidermal growth factor and growth hormone-releasing peptide-6: Combined therapeutic approach in experimental stroke
Authors: García del Barco-Herrera Diana , Martínez Nelvys Subirós , Coro-Antich Rosa María , Machado Jorge Martín , Alba José Suárez , Salgueiro Sandra Rodríguez , Acosta Jorge Berlanga
Published: December 2019

Purpose: Stroke is the second cause of mortality worldwide, with a high incidence of disability in survivors. Promising candidate drugs have failed in stroke trials. Combined therapies are attractive strategies that simultaneously target different points of stroke pathophysiology. The aim of this work is to determine whether the combined effects of Epidermal Growth Factor (EGF) and Growth Hormone-Releasing Peptide-6 (GHRP6) can attenuate clinical signs and pathology in an experimental stroke model. Methods: Brain global ischemia was generated in Mongolian gerbils by 15 minutes of carotid occlusion. After reperfusion, EGF, GHRP6 or EGF+GHRP6 were intraperitoneally administered. Clinical manifestations were monitored daily. Three days after reperfusion, animals were anesthetized and perfused with an ink solution. The anatomy of the Circle of Willis was characterized. Infarct volume and neuronal density were analyzed. Results: EGF+GHRP6 co-administration reduced clinical manifestations and infarct volume and preserved neuronal density. No correlation was observed between the grade of anastomosis of the Circle of Willis and clinical manifestations in the animals receiving EGF+GHRP6, as opposed to the vehicle-treated gerbils. Conclusions: Co-treatment with EGF and GHRP6 affects both the clinical and pathological outcomes in a global brain ischemia model, suggesting a suitable therapeutic approach for the acute management of stroke.
Towards physiological ankle movements with the ActiGait implantable drop foot stimulator in chronic stroke
Authors: Ernst Jennifer , Grundey Jessica , Hewitt Manuel , von Lewinski Friederike , Kaus Jürgen , Schmalz Thomas , Rohde Veit , Liebetanz David
Published: December 2019

Purpose: Functional electrical stimulation represents an alternative to conventional and passive ankle foot orthosis (AFO) for the treatment of stroke-related drop foot. We evaluated the implantable 4-channel stimulator ActiGait, which selectively and directly stimulates the peroneal nerve. In addition, it bypasses the need for surface electrodes and cables. Methods: Walking speed (10-meter gait test, [m/s]) and walking endurance (6-minute gait test [m/6min]) of 5 patients were tested prior to, as well as 6 and 12 weeks after, the implantation of the ActiGait implantable drop foot stimulator system. In addition, ankle joint angles were assessed during specific phases of the gait cycle, i.e. initiation angle (IA) at the first contact of the foot to the floor, initial plantar flexion (IPF), dorsiflexion (DF) and final plantar flexion (FPF) in [°] during stance phase. The ankle joint angles were measured at baseline and 12 weeks after ActiGait implantation. Results: At the first follow-up, patients' gait speed was found to have increased (0.55; 0.77 m/s) as had walking endurance (211; 260 m). Improvement in gait speed (0.55; 0.77 m/s) and endurance (214; 248 m) was still present after 12 weeks. In addition, gait analysis after 12 weeks revealed a nearly normal physiological initiation angle (113° vs 122°) and an increase in the initial plantar flexion (7° vs. 0°). The initiation angle (IA) represents a well-suited parameter for adequate pre-positioning of the foot at the beginning of the stance phase and is necessary to prevent stumbling and falling. Furthermore, IA is identical to the maximum achieved dorsiflexion during the swing phase of gait. Thus, analysis of the IA of subjects walking with the implantable drop foot stimulator systems ActiGait is particularly useful in showing that the implantable system restores the IA towards physiological ankle movements. Conclusion: The ActiGait system increased gait speed, walking endurance and the physiology of important ankle joint kinematics. This is most likely a result of ankle dorsiflexion by active peroneal stimulation during the swing phase of gait and optimized prepositioning (IA) of the foot at the beginning of stance phase. The ActiGait system represents a therapeutic option for the treatment of patients suffering drop foot due to a cerebrovascular insult.
The impact of enriched environment and transplantation of murine cortical embryonic stem cells on recovery from controlled cortical contusion injury
Authors: Peruzzaro Sarah T. , Gallagher Jonathan , Dunkerson Jacob , Fluharty Sarah , Mudd David , Hoane Michael R. , Smith Jeffrey S.
Published: December 2019

Purpose: The effectiveness of embryonic stem cell (eSC) therapy has been explored in many models of neurological disease and several research groups have shown that eSC treatment leads to improved outcomes in pre-clinical models of traumatic brain injury (TBI). Though functional recovery occurs, few surviving eSCs appear to develop neuronal characteristics; instead the majority of the surviving eSC express glial phenotypes. Additionally, researchers have shown that enriching the post-surgical environment of the subject promotes functional recovery following TBI. The purpose of the current project was to determine if post-surgical environmental enrichment (EE) impacts the survival, migration, and integration of eSCs in a rodent model of TBI and if the presence of these cells lead to improved outcomes. Methods: In the current study, the medial frontal cortex (MFC) of rats was injured using a controlled cortical impact (CCI) device. Immediately following injury the rats were placed into either EE or standard environment (SE) housing and then seven days post-injury rats received either murine cortical eSC or media. Behavioral testing consisted of the Morris water maze (MWM), Barnes Maze (BM), and Rotarod tasks (RR). Results: On the MWM task, TBI/eSC/EE animals performed as well as the Sham/SE and Sham/EE groups. The TBI/eSC/SE, TBI/Media/EE, and TBI/Media/SE groups were impaired compared to the controls. By the end of training on the BM there were no differences between the Sham, TBI/Media/EE, and TBI/eSC/EE groups. On the RR task all animals placed in the EE performed equally well and significantly better than their SE housed counterparts. By the end of training on the RR task, the TBI/eSC/EE group performed as well as the sham counterparts, and though not significant they also surpassed the performance of the injured animals that received enrichment or eSC treatment alone. Conclusions: Combing therapeutic strategies with enriching the post-injury environment is likely to be an important addition to determining the efficacy of pre-clinical therapies.
Effects of a novel herbal formulation JSK on acute spinal cord injury in rats
Authors: Su Caixin , Zhang Donald , Truong John , Jiang Cai , Lee Sam , Jarouche Mariam , Hennell James R. , Rathbone Michel P. , Sucher Nikolaus J. , Jiang Shucui
Published: December 2019

Purpose: Acute spinal cord injury (SCI) triggers multiple cellular and molecular pathways; therapy aimed at only one pathway is unlikely to succeed. Anecdotal reports indicate that a novel herbal formulation (JSK—Ji-Sui-Kang) may enhance recovery in humans with SCI. We investigated whether JSK's therapeutic effects could be verified in a well-established SCI model in rats. Methods: Therapeutic effects of JSK were tested using a standard behavioral assessment, histological, immunochemical and microarray analysis. Phytochemical fingerprinting of JSK was performed using high performance liquid chromatography coupled with photodiode array detection and electrospray ionization-mass spectrometry. JSK or vehicle was gavaged to rats 24 hours after SCI and daily thereafter for 3 weeks. Results: Locomotor function significantly improved (n = 12; p < 0.05), tissue damage was reduced (p < 0.01; n = 6) and more axons and myelin were observed in JSK-treated compared with vehicle control animals. JSK significantly enhanced expression of neuroglobin, vascular endothelial growth factor and growth-associated protein 43, and reduced the expression of caspase 3, cyclooxygenase-2, RhoA (p < 0.05; n = 6) and fibrinogen (p < 0.01; n = 6). RNA microarray indicated that JSK altered transcription of genes involved in ischemic and inflammatory/immune responses and apoptosis (p < 0.05; n = 3). Conclusions: JSK appears to target multiple biochemical and cellular pathways to enhance functional recovery and improve outcomes of SCI. The results provide a basis for further investigation of JSK's effects following SCI.
Immunohistochemical characterization of axonal sprouting in mice
Authors: Feeney Erin J. , Stephenson Diane , Kleiman Robin , Bove Susan , Cron Courtney , Moody Lara , Robinson Mercedes , Ramirez Julio J.
Published: December 2019

Purpose: Transgenic manipulation of mouse physiology facilitates the preclinical study of genetic risk factors, neural plasticity, and reactive processes accompanying Alzheimer's disease. Alternatively, entorhinal cortex lesions (ECLs) model pathophysiological denervation and axonal sprouting in rat. Given reports of anatomical differences between the mouse and rat hippocampus, application of the ECL paradigm to transgenic mice first requires comprehensive characterization of axonal sprouting in the wild-type. Methods: Adult male C57BL/6 mice sustained unilateral transections of the perforant pathway. Subjects were sacrificed at 1, 4, 10, 18, and 28 days postlesion, and hippocampal sections were stained for AChE, the postsynaptic terminal marker drebrin, and the presynaptic terminal proteins SNAP-25, GAP-43, synapsin, and synaptophysin. To examine synaptic turnover and reinnervation, ipsilateral-to-contralateral staining densities were determined within the dentate molecular layer, and shrinkage-corrected ratios were compared to 28 day-yoked sham cases. Results: At 28 days postlesion, ipsilateral terminal marker densities exhibited significant depression. In contrast, qualitative analyses at earlier time points suggested altered AChE staining patterns and increased SNAP-25 and synapsin immunoreactivity in the inner molecular layer (IML) of the dentate gyrus. Conclusions: C57BL/6 mice exhibit synaptic reorganization following perforant path transections. The IML may provide a key target for evaluation and intervention in ECL mouse models.
TMS and tDCS in post-stroke aphasia: Integrating novel treatment approaches with mechanisms of plasticity
Authors: Torres Jose , Drebing Daniel , Hamilton Roy
Published: December 2019

Aphasia is a common result of stroke, affecting over one million Americans. Currently, intensive speech therapy is the mainstay of treatment, although its efficacy has been variable at best. Recent years have seen the emergence of non-invasive brain stimulation, specifically Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), as potential treatments for post-stroke aphasia. A growing body of investigations has shown the efficacy of both modalities in facilitating recovery from chronic aphasia, while data regarding subacute aphasia are much more limited and evidence in the acute post-stroke phase are still lacking. Much remains unknown about how these techniques cause clinical improvement or about their long-term efficacy, side-effects, and safety. In this article, we examine the data demonstrating the safety and efficacy of TMS and tDCS, discuss the major differences between them, and consider how those differences may inform the use of each modality. We also consider the different models of neuroplasticity in the setting of post-stroke aphasia and how these models may influence when and in which patients each modality would impart the most benefit.
Transpalpebral electrotherapy for dry age-related macular degeneration (AMD): An exploratory trial
Authors: Anastassiou Gerasimos , Schneegans Anna-Lena , Selbach Michael , Kremmer Stephan
Published: December 2019

Purpose: To evaluate the effect of transpalpebral electrotherapy on patients with dry age-related macular degeneration (AMD). Methods: 22 patients were randomized in two groups to either receive therapy (n = 12) or placebo (n = 10). There was no statistically significant difference for age and initial visual acuity (VA) between the two groups (p = 0.6; ANOVA). Treatment was performed on 5 consecutive days. On each day two sessions were applied. Every session included 8 spots (40 sec/spot) around the eye globe. The current applied (changing frequency 5–80 Hz) varied individually between 150 and 220 μA. Patients were examined before treatment, at the end of the 5-day treatment period, after 4 weeks and at 6 months. Examinations included a standardized VA testing, using ETDRS letters, contrast sensitivity, macular sensitivity and fixation stability using microperimetry and measurements with SD-OCT. Results: At the end of week 1, mean VA improved markedly (p = 0.001; T test), with 7 out of 12 patients showing an improvement of more than 5 letters. After 4 weeks, there was an improvement of more than 10 letters in 3 patients (mean + 5.7 letters; p = 0.001; T test) whereas at 6 months a loss of 1.6 letters was observed. Only 4 (33%) of our patients did not show any improvement at all. Contrast sensitivity displayed a similar pattern. Within one week after treatment, there was a rapid improvement (+4.4 optotypes; p = 0.006; T test). After 6 months, contrast sensitivity declined again (+1.5 optotypes; p = 0.2; T test). Compared to the placebo group changes on VA failed statistical significance (p = 0.1 at 4 week; T test) whereas changes on contrast sensitivity were statistically significant (p = 0.01 at week 4; T test). No adverse events were seen or reported during the study period. Conclusions: To the best of our knowledge, this is the first report of a transpalpebral electrostimulation in patients with dry AMD that demonstrates a temporary increase in visual function in some of these patients; results that seem to justify further research on this potential treatment option for dry AMD.
Stereotactic planning software for human neurotransplantation: Suitability in 22 surgical cases of Huntington's disease
Authors: Lopez William Omar Contreras , Nikkhah Guido , Schültke Elisabeth , Furlanetti Luciano , Trippel Michael
Published: December 2019

Purpose: Intrastriatal neural transplantation using multiple grafts is an experimental approach to the treatment of Huntington's disease (HD). Brain atrophy makes stereotactic plans in these patients a tedious procedure with a risk of suboptimal spatial distribution of the grafts in transplantation procedures. Here we present a self-developed software to optimize the surgical stereotactic planning for bilateral neurotransplantation procedures. It allows close to symmetrical distribution of the stereotactic coordinates in relation to the mid-commissural point (MCP), proposing automatically the planning coordinates for the first transplanted hemisphere and mirrored coordinates to be used in the contra-lateral hemisphere. Methods: Twenty-two consecutive HD patients underwent bilateral stereotactic striatal transplantation. Two caudate nucleus and four putaminal tracks were planned bilaterally. For the second, contra-lateral transplantation, the coordinates were mirrored in order to determine contralateral targets and trajectories. Intra-individual comparison between software given coordinates and finally used coordinates was performed. Results: No statistical significance was found comparing a) the differences between coordinates proposed by the software and the final coordinates and b) the distribution of the transplantation sites in relation to the midline for the right vs. left hemisphere. No intra- or postoperative transplantation-related adverse events occurred. Conclusions: The use of model-based and mirrored coordinates allowed optimal spatial distribution of the grafts. Minor changes were required comparing right to left coordinates giving proof-of principle. The initial use of the software suggests that it may be useful in experimental transplantation trials where neural cell grafts are to be implanted into predefined target sites in the human brain, whether unilateral or bilateral.