Damage To Pathways Research Articles

Molecular Aspects in the Development of Type 2 Diabetes and Possible Preventive and Complementary Therapies.

The incidence of diabetes, including type 2 diabetes (T2DM), is increasing sharply worldwide. To reverse this, more effective approaches in prevention and treatment are needed. In our review, we sought to summarize normal insulin action and the pathways that primarily influence the development of T2DM. Normal insulin action involves mitogenic and metabolic pathways, as both are important in normal metabolic processes, regeneration, etc. However, through excess energy, both can be hyperactive or attenuated/inactive leading to disturbances in the cellular and systemic regulation with the consequence of cellular stress and systemic inflammation. In this review, we detailed the beneficial molecular changes caused by some important components of nutrition and by exercise, which act in the same molecular targets as the developed drugs, and can revert the damaged pathways. Moreover, these induce entire networks of regulatory mechanisms and proteins to restore unbalanced homeostasis, proving their effectiveness as preventive and complementary therapies. These are the main steps for success in prevention and treatment of developed diseases to rid the body of excess energy, both from stored fats and from overnutrition, while facilitating fat burning with adequate, regular exercise in healthy people, and together with necessary drug treatment as required in patients with insulin resistance and T2DM.

Perspectives for the application of neurogenetic research in programming Neurorehabilitation.

Certain genetic variants underlie the proper functioning of the nervous system. They affect the nervous system in all aspects - molecular, systemic, cognitive, computational and sensorimotor. The greatest changes in the nervous system take place in the process of its maturation in the period of psychomotor development, as well as during neurorehabilitation, the task of which is to rebuild damaged neuronal pathways, e.g. by facilitating movement or training cognitive functions. Certain genetic polymorphisms affect the effectiveness of the processes of reconstruction or restoration of neural structures, which is clearly reflected in the effects of neurorehabilitation. This review presents the perspectives for the application of neurogenetic research in programming neurorehabilitation by determining the relationship of as many as 16 different genetic polymorphisms with specific functions of importance in rehabilitation. Thanks to this broad view, it may be possible to predict the effectiveness of rehabilitation on the basis of genetic testing, which would significantly contribute to the development of personalized medicine and to the optimal management of medical services in healthcare systems.

Advanced deep learning method for Aerial image segmentation of landscape changes in pre-and post-disaster scenarios

<p>The precise analysis of conditions in the landscape before and aftermath of the disaster is a mandatory challenge in aerial image landscape monitoring. The change in patterns of landscape, damaged pathways, and damaged areas will have a major impact without monitoring and redevelopment. Therefore, semantic segmentation of the landscape is required in order to analyze the changes and avoid other risks in pre-and post-disaster scenarios. To address these queries a deep learning-based landscape monitoring method is presented in this work. A Gated Shaped Convolution Neural Network is utilized for the semantic segmentation of the aerial landscape images. Initially the aerial image undergoes pre-processing with the process of dilation and GSCNN emphasize the shaped and boundary masks of the affected landscape. To choose the best possible pathways and solutions for development the GSCNN undergoes the particle swarm optimization. In the present study, the proposed PSO-GSCNN is evaluated by comparing the accuracy, precision, and recall of the proposed method with Restricted Boltzmann Machines (RBMs), Convolutional Neural Networks, and Fuse-Net segmentation methods. In comparison with conventional RSM, CNN, and Fuse-Net, the accuracy rate of the model is 97.65%, the precision rate is 98.21%, and the recall rate is 97.23%. This technique has achieved 97.66% accuracy, 97% precision, and 96% recall, all higher than the existing methods.</p>

Valérie Biousse: a leader in neuro-ophthalmology

Valérie Biousse: a leader in neuro-ophthalmology

Pseudobulbar affect as an early manifestation of HIV-related toxoplasmosis

IntroductionPseudobulbar affect (PBA) is an emotional disorder characterized by uncontrollable outbursts of laughing and/or crying. It is caused by lesions that damage pathways in the frontal lobe and descending to the brain stem, basis pontis and cerebellum. The main causes are neurodegenerative diseases.ObjectivesTo present a case of PBA secondary to cerebral toxoplasmosis.MethodsThe present study is a case report of a patient admitted for HIV-related toxoplasmosis to our hospital. We also researched previous case reports of PBA secondary to CNS infection using a pubmed query.ResultsMr. JA is a 38-year-old male, with no prior psychiatric or medical history. He reported having had same-sex sexual encounters previously. He was admitted for ataxia and dysarthria in a medical unit, and diagnosed of HIV infection, with a CD4 count of 19 cells/μL. The MRI showed a lesion of 22x19x18mm with ring enhancement predominantly in basis pontis, compatible with toxoplasmosis(Image1). Treatment with sulfadiazine, pyrimethamine and dexamethasone was initiated. After five days of hospitalization he was referred to Consultation-Liaison Psychiatry for involuntary and uncontrollable outbursts of laughing and crying, insomnia, but no other psychopathological symptoms. Therefore, citalopram 20mg per day was started, with reduction on the frequency of outbursts.ConclusionsThe clinical presentation suggested the diagnosis of PBA due to cerebral toxoplasmosis. Although we found no previous reports of PBA related to HIV infection or toxoplasmosis, the location of the toxoplasmosis lesion is congruent with the typical damaged pathways in PBA. To our knowledge, this is the first report about PBA secondary to HIV-related toxoplasmosis.DisclosureNo significant relationships.

Epigenetic Profiling in the Saliva of Obese Pregnant Women.

Maternal obesity is associated with inflammation and oxidative stress, strongly impacting the intrauterine environment with detrimental consequences for both mother and offspring. The saliva is a non-invasive biofluid reflecting both local and systemic health status. This observational study aimed to profile the epigenetic signature in the saliva of Obese (OB) and Normal-Weight (NW) pregnant women. Sixteen NW and sixteen OB Caucasian women with singleton spontaneous pregnancies were enrolled. microRNAs were quantified by the OpenArray Platform. The promoter region methylation of Suppressor of Cytokine Signaling 3 (SOCS3) and Transforming Growth Factor Beta 1 (TGF-Beta1) was assessed by pyrosequencing. There were 754 microRNAs evaluated: 20 microRNAs resulted in being differentially expressed between OB and NW. microRNA pathway enrichment analysis showed a significant association with the TGF-Beta signaling pathway (miTALOS) and with fatty acids biosynthesis/metabolism, lysine degradation, and ECM–receptor interaction pathways (DIANA–miRPath). Both SOCS3 and TGF-Beta1 were significantly down-methylated in OB vs. NW. These results help to clarify impaired mechanisms involved in obesity and pave the way for the understanding of specific damaged pathways. The characterization of the epigenetic profile in saliva of pregnant women can represent a promising tool for the identification of obesity-related altered mechanisms and of possible biomarkers for early diagnosis and treatment of pregnancy-adverse conditions.

Early white matter connectivity and plasticity in post stroke aphasia recovery

A disruption of white matter connectivity is negatively associated with language (recovery) in patients with aphasia after stroke, and behavioral gains have been shown to coincide with white matter neuroplasticity. However, most brain-behavior studies have been carried out in the chronic phase after stroke, with limited generalizability to earlier phases. Furthermore, few studies have investigated neuroplasticity patterns during spontaneous recovery (i.e., not related to a specific treatment) in the first months after stroke, hindering the investigation of potential early compensatory mechanisms. Finally, the majority of previous research has focused on damaged left hemisphere pathways, while neglecting the potential protective value of their right hemisphere counterparts for language recovery. To address these outstanding issues, we present a longitudinal study of thirty-two patients with aphasia (21 males and 11 females, M = 69.47 years, SD = 10.60 years) who were followed up for a period of 1 year with test moments in the acute (1–2 weeks), subacute (3–6 months) and chronic phase (9–12 months) after stroke. Constrained Spherical Deconvolution-based tractography was performed in the acute and subacute phase to measure Fiber Bundle Capacity (FBC), a quantitative connectivity measure that is valid in crossing fiber regions, in the bilateral dorsal arcuate fasciculus (AF) and the bilateral ventral inferior fronto-occipital fasciculus (IFOF). First, concurrent analyses revealed positive associations between the left AF and phonology, and between the bilateral IFOF and semantics in the acute – but not subacute - phase, supporting the dual-stream language model. Second, neuroplasticity analyses revealed a decrease in connection density of the bilateral AF – but not the IFOF – from the acute to the subacute phase, possibly reflecting post stroke white matter degeneration in areas adjacent to the lesion. Third, predictive analyses revealed no contribution of acute FBC measures to the prediction of later language outcomes over and above the initial language scores, suggesting no added value ofthe diffusion measures for languageprediction. Our study provides new insights on (changes in) connectivity of damaged and undamaged language pathways in patients with aphasia in the first months after stroke, as well as if/how such measures are related to language outcomes at different stages of recovery. Individual results are discussed in the light of current frameworks of language processing and aphasia recovery.

A Dual TLR7/TLR9 Inhibitor HJ901 Inhibits ABC-DLBCL Expressing the MyD88 L265P Mutation.

Diffuse large B cell lymphoma (DLBCL) is associated with aggressive clinical cases and poor prognosis despite recent advances in disease treatment. In activated B-cell-like (ABC)-DLBCL, the most severe damaged signaling pathways converge to aberrantly activate the Toll-like receptor (TLR) 7/9/MyD88 pathways, leading to the avoidance of cell death and resistance to chemotherapy. A gain of function mutation in MyD88 (MyD88 L265P) enhanced the NF-κB and JAK-STAT signaling pathways and was associated with dysregulation of TLR signaling in the pathogenesis of ABC-DLBCL. Therefore, inhibition of the TLR signaling network may improve clinical outcomes. In this study, we designed a de novo synthesized oligodeoxynucleotide-based antagonist of TLR7 and TLR9, referred to as HJ901, which competitively binds to TLR7/9. We profiled HJ901 inhibition in various DLBCL cell lines and verified tumor suppression in a xenograft mouse model. We found that HJ901 treatment significantly reduced TLR7- and TLR9-mediated cell proliferation and cytokine production in a time- and dose-dependent manner in various DLBCL cell lines expressing the MyD88 L265P mutation. Moreover, HJ901 prevented tumor growth and downregulated the NF-κB and JAK2-STAT3 signaling pathways in a DLBCL xenograft mouse model with the MyD88 L265P mutation. These results reveal that the anti-tumor effects of the synthesized oligodeoxynucleotide-based antagonist, HJ901, which competitively binds to TLR7/9, may be associated with the downregulation of the NF-κB and JAK2-STAT3 signaling pathways and provide rationale for treating ABC-DLBCL patients with the MyD88 L265P mutation.

Evaluation of pavement condition index by different methods: Case study of Maringá, Brazil

In order to speed up and prioritize investments in pavement recovery, it is necessary to perform localization and characterization studies of the defects. Thus, the objectives of this study were to analyze the objective and subjective evaluations of the Pavement Condition Index (PCI) used in the Urban Pavement Management System (UPMS) using GIS and identify the most damaged pathways. This research was carried out in the state of Paraná (PR), Brazil. A functional evaluation was performed, with defect identification by means of visual analysis using the PCI method. Two types of evaluation were performed, objective and subjective, which were compared to each other using the coefficient of Pearson's correlation. Subsequently, maps were generated in the ArcGIS 10.2 software. It was observed that 92.21% of the sections were classified as “very good” to “fair,” whereas 7.94% were classified as “poor” or “very poor”. It was possible to prove the similarity between the results of the objective and subjective evaluations from Pearson's correlation. The coefficient resulted in 0.95, a value close to 1 which represents a strong correlation between the data. Thus, the PCI can be determined more quickly and simply through subjective evaluations. Subjective evaluations are indicated for cities where maintenance is performed without any planning, it is a simplified way to evaluate the pavement and have good results. The use of the GIS tool facilitated the visualization of the pavement conditions in the different sections.

Integrated Analysis of Transcriptomic Data Reveals Key Anti-CKD Targets and Anti-ESRD Targets

Chronic kidney disease (CKD) is a kidney disease in which there is gradual loss of kidney function over time and end-stage renal disease (ESRD) is the final stage of CKD. Both CKD and ESRD are worldwide health problems with a high economic cost to health systems. However, the molecular mechanisms of the development of CKD and ESRD remain poorly understood. This study aimed to systematically elucidate the molecular mechanisms of the development of CKD and ESRD. Transcriptome data of CKD and ESRD were downloaded from the NCBI-GEO database. Differentially expressed genes between cases and controls (chronic kidney disease patients vs. controls, end-stage renal disease patients vs. controls) were calculated using the empirical Bayes algorithm. Gene set enrichment analysis (GSEA) was used for analyzing the KEGG pathway difference between cases and controls. Furthermore, CKD and ESRD target genes were obtained from the Thomson Reuters Integrity database. Tissue-specific gene interaction network analysis was performed using the GIANT web server. There were multiple damaged pathways in ESRD but only a few pathways were disturbed in CKD. Furthermore, we identified 9 dysregulated anti-ESRD genes but no dysregulated anti-CKD genes. Network analysis revealed that the NF-kB signaling pathway was essential for ESRD. This study revealed several crucial anti-ESRD genes that are involved in the regulation of the NF-kB signaling pathway. This information may be helpful for the treatment of ESRD.

Development of an EMG-Controlled Serious Game for Rehabilitation.

A majority of the seven million stroke survivors in the U.S. have hand impairments, adversely affecting performance of a variety of activities of daily living, because of the fundamental role of the hand in performing functional tasks. Disability in stroke survivors is largely attributable to damaged neuronal pathways, which result in inappropriate activation of muscles, a condition prevalent in distal upper extremity muscles following stroke. While conventional rehabilitation methods focus on the amplification of existing muscle activation, the effectiveness of therapy targeting the reorganization of pathological activation patterns is often unexplored. To encourage modulation of activation level and exploration of the activation workspace, we developed a novel platform for playing a serious game through electromyographic control. This system was evaluated by a group of neurologically intact subjects over multiple sessions held on different days. Subjects were assigned to one of two groups, training either with their non-dominant hand only (unilateral) or with both hands (bilateral). Both groups of subjects displayed improved performance in controlling the cursor with their non-dominant hand, with retention from one session to the next. The system holds promise for rehabilitation of control of muscle activation patterns.

Collagen-chitosan scaffold impregnated with bone marrow mesenchymal stem cells for treatment of traumatic brain injury.

Combinations of biomaterials and cells can effectively target delivery of cells or other therapeutic factors to the brain to rebuild damaged nerve pathways after brain injury. Porous collagen-chitosan scaffolds were prepared by a freeze-drying method based on brain tissue engineering. The scaffolds were impregnated with rat bone marrow mesenchymal stem cells. A traumatic brain injury rat model was established using the 300 g weight free fall impact method. Bone marrow mesenchymal stem cells/collagen-chitosan scaffolds were implanted into the injured brain. Modified neurological severity scores were used to assess the recovery of neurological function. The Morris water maze was employed to determine spatial learning and memory abilities. Hematoxylin-eosin staining was performed to measure pathological changes in brain tissue. Immunohistochemistry was performed for vascular endothelial growth factor and for 5-bromo-2-deoxyuridine (BrdU)/neuron specific enolase and BrdU/glial fibrillary acidic protein. Our results demonstrated that the transplantation of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds to traumatic brain injury rats remarkably reduced modified neurological severity scores, shortened the average latency of the Morris water maze, increased the number of platform crossings, diminished the degeneration of damaged brain tissue, and increased the positive reaction of vascular endothelial growth factor in the transplantation and surrounding areas. At 14 days after transplantation, increased BrdU/glial fibrillary acidic protein expression and decreased BrdU/neuron specific enolase expression were observed in bone marrow mesenchymal stem cells in the injured area. The therapeutic effect of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds was superior to stereotactic injection of bone marrow mesenchymal stem cells alone. To test the biocompatibility and immunogenicity of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds, immunosuppressive cyclosporine was intravenously injected 12 hours before transplantation and 1-5 days after transplantation. The above indicators were similar to those of rats treated with bone marrow mesenchymal stem cells and collagen-chitosan scaffolds only. These findings indicate that transplantation of bone marrow mesenchymal stem cells in a collagen-chitosan scaffold can promote the recovery of neuropathological injury in rats with traumatic brain injury. This approach has the potential to be developed as a treatment for traumatic brain injury in humans. All experimental procedures were approved by the Institutional Animal Investigation Committee of Capital Medical University, China (approval No. AEEI-2015-035) in December 2015.

Metabolic repair through emergence of new pathways in Escherichia coli

Escherichia coli can derive all essential metabolites and cofactors through a highly evolved metabolic system. Damage of pathways may affect cell growth and physiology, but the strategies by which damaged metabolic pathways can be circumvented remain intriguing. Here, we use a ΔpanD (encoding for aspartate 1-decarboxylase) strain of E. coli that is unable to produce the β-alanine required for CoA biosynthesis to demonstrate that metabolic systems can overcome pathway damage by extensively rerouting metabolic pathways and modifying existing enzymes for unnatural functions. Using directed cell evolution, rewiring and repurposing of uracil metabolism allowed formation of an alternative β-alanine biosynthetic pathway. After this pathway was deleted, a second was evolved that used a gain-of-function mutation on ornithine decarboxylase (SpeC) to alter reaction and substrate specificity toward an oxidative decarboxylation-deamination reaction. After deletion of both pathways, yet another independent pathway emerged using polyamine biosynthesis, demonstrating the vast capacity of metabolic repair.

Assessing functional connectivity across 3D tissue engineered axonal tracts using calcium fluorescence imaging

Objective. Micro-tissue engineered neural networks (micro-TENNs) are anatomically-inspired constructs designed to structurally and functionally emulate white matter pathways in the brain. These 3D neural networks feature long axonal tracts spanning discrete neuronal populations contained within a tubular hydrogel, and are being developed to reconstruct damaged axonal pathways in the brain as well as to serve as physiologically-relevant in vitro experimental platforms. The goal of the current study was to characterize the functional properties of these neuronal and axonal networks. Approach. Bidirectional micro-TENNs were transduced to express genetically-encoded calcium indicators, and spontaneous fluorescence activity was recorded using real-time microscopy at 20 Hz from specific regions-of-interest in the neuronal populations. Network activity patterns and functional connectivity across the axonal tracts were then assessed using various techniques from statistics and information theory including Pearson cross-correlation, phase synchronization matrices, power spectral analysis, directed transfer function, and transfer entropy. Main results. Pearson cross-correlation, phase synchronization matrices, and power spectral analysis revealed high values of correlation and synchronicity between the spatially segregated neuronal clusters connected by axonal tracts. Specifically, phase synchronization revealed high synchronicity of >0.8 between micro-TENN regions of interest. Normalized directed transfer function and transfer entropy matrices suggested robust information flow between the neuronal populations. Time varying power spectrum analysis revealed the strength of information propagation at various frequencies. Signal power strength was visible at elevated peak levels for dominant delta (1–4 Hz) and theta (4–8 Hz) frequency bands and progressively weakened at higher frequencies. These signal power strength results closely matched normalized directed transfer function analysis where near synchronous information flow was detected between frequencies of 2–5 Hz. Significance. To our knowledge, this is the first report using directed transfer function and transfer entropy methods based on fluorescent calcium activity to estimate functional connectivity of distinct neuronal populations via long-projecting, 3D axonal tracts in vitro. These functional data will further improve the design and optimization of implantable neural networks that could ultimately be deployed to reconstruct the nervous system to treat neurological disease and injury.

Case Report: Scrambler Therapy for the Treatment of Chronic Post-Mastectomy Pain (cPMP)

Chronic post-mastectomy pain (cPMP), including post-lumpectomy pain, is common with no established ways of treatment. We treated three consecutive patients referred with cPMP with scrambler therapy (ST), a non-invasive electrical neurocutaneous stimulation. Treatment was given across the area of pain following the dermatomes for 45 minutes daily, for several consecutive days until relief, and then was repeated as needed. The ST MC5A device synthesizes 16 different waveforms that resemble action potentials, delivered to the surface receptors of the c-fibers, to send “non-pain” information along the damaged pathways to reduce central sensitization. All three had marked (over 75%) and sustained (months) reduction of allodynia, hyperalgesia, and pain. All reported marked improvements in their quality of life and normal function. One woman was able to stop chronic opioid use. No side effects were observed.Scrambler therapy is a promising way to relieve cancer and other types of neuropathic pain, and may be helpful in cPMP. Further prospective trials are warranted.

A Delay between Motor Cortex Lesions and Neuronal Transplantation Enhances Graft Integration and Improves Repair and Recovery.

We previously reported that embryonic motor cortical neurons transplanted immediately after lesions in the adult mouse motor cortex restored damaged motor cortical pathways. A critical barrier hindering the application of transplantation strategies for a wide range of traumatic injuries is the determination of a suitable time window for therapeutic intervention. Here, we report that a 1 week delay between the lesion and transplantation significantly enhances graft vascularization, survival, and proliferation of grafted cells. More importantly, the delay dramatically increases the density of projections developed by grafted neurons and improves functional repair and recovery as assessed by intravital dynamic imaging and behavioral tests. These findings open new avenues in cell transplantation strategies as they indicate successful brain repair may occur following delayed transplantation.SIGNIFICANCE STATEMENT Cell transplantation represents a promising therapy for cortical trauma. We previously reported that embryonic motor cortical neurons transplanted immediately after lesions in the adult mouse motor cortex restored damaged cortical pathways. A critical barrier hindering the application of transplantation strategies for a wide range of traumatic injuries is the determination of a suitable time window for therapeutic intervention. We demonstrate that a 1 week delay between the lesion and transplantation significantly enhances graft vascularization, survival, proliferation, and the density of the projections developed by grafted neurons. More importantly, the delay has a beneficial impact on functional repair and recovery. These results impact the effectiveness of transplantation strategies in a wide range of traumatic injuries for which therapeutic intervention is not immediately feasible.

Evaluation of Gene Therapy as an Intervention Strategy to Treat Brain Injury from Stroke

Stroke is a leading cause of death and disability, with a lack of treatments available to prevent cell death, regenerate damaged cells and pathways, or promote neurogenesis. The extended period of hours to weeks over which tissue damage continues to occur makes this disorder a candidate for gene therapy. This review highlights the development of gene therapy in the area of stroke, with the evolution of viral administration, in experimental stroke models, from pre-injury to clinically relevant timeframes of hours to days post-stroke. The putative therapeutic proteins being examined include anti-apoptotic, pro-survival, anti-inflammatory, and guidance proteins, targeting multiple pathways within the complex pathology, with promising results. The balance of findings from animal models suggests that gene therapy provides a viable translational platform for treatment of ischemic brain injury arising from stroke.

Rebuilding Brain Circuitry with Living Micro-Tissue Engineered Neural Networks.

Prominent neuropathology following trauma, stroke, and various neurodegenerative diseases includes neuronal degeneration as well as loss of long-distance axonal connections. While cell replacement and axonal pathfinding strategies are often explored independently, there is no strategy capable of simultaneously replacing lost neurons and re-establishing long-distance axonal connections in the central nervous system. Accordingly, we have created micro-tissue engineered neural networks (micro-TENNs), which are preformed constructs consisting of long integrated axonal tracts spanning discrete neuronal populations. These living micro-TENNs reconstitute the architecture of long-distance axonal tracts, and thus may serve as an effective substrate for targeted neurosurgical reconstruction of damaged pathways in the brain. Cerebral cortical neurons or dorsal root ganglia neurons were precisely delivered into the tubular constructs, and properties of the hydrogel exterior and extracellular matrix internal column (180-500 μm diameter) were optimized for robust neuronal survival and to promote axonal extensions across the 2.0 cm tube length. The very small diameter permits minimally invasive delivery into the brain. In this study, preformed micro-TENNs were stereotaxically injected into naive rats to bridge deep thalamic structures with the cerebral cortex to assess construct survival and integration. We found that micro-TENN neurons survived at least 1 month and maintained their long axonal architecture along the cortical-thalamic axis. Notably, we also found neurite penetration from micro-TENN neurons into the host cortex, with evidence of synapse formation. These micro-TENNs represent a new strategy to facilitate nervous system repair by recapitulating features of neural pathways to restore or modulate damaged brain circuitry.

Onset Latency of Motor Evoked Potentials in Motor Cortical Mapping with Neuronavigated Transcranial Magnetic Stimulation.

Cortical motor mapping in pre-surgical applications can be performed using motor evoked potential (MEP) amplitudes evoked with neuronavigated transcranial magnetic stimulation. The MEP latency, which is a more stable parameter than the MEP amplitude, has not so far been utilized in motor mapping. The latency, however, may provide information about the stress in damaged motor pathways, e.g. compression by tumors, which cannot be observed from the MEP amplitudes. Thus, inclusion of this parameter could add valuable information to the presently used technique of MEP amplitude mapping. In this study, the functional cortical representations of first dorsal interosseous (FDI), abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles were mapped in both hemispheres of ten healthy righthanded volunteers. The cortical muscle representations were evaluated by the area and centre of gravity (CoG) by using MEP amplitudes and latencies. As expected, the latency and amplitude CoGs were congruent and were located in the centre of the maps but in a few subjects, instead of a single centre, several loci with short latencies were observed. In conclusion, MEP latencies may be useful in distinguishing the cortical representation areas with the most direct pathways from those pathways with prolonged latencies. However, the potential of latency mapping to identify stressed motor tract connections at the subcortical level will need to be verified in future studies with patients.

Acute theophylline exposure modulates breathing activity through a cervical contusion

Cervical spinal contusion injuries are the most common form of spinal cord injury (>50%) observed in humans. These injuries can result in the impaired ability to breathe. In this study we examine the role of theophylline in the rescue of breathing behavior after a cervical spinal contusion. Previous research in the C2 hemisection model has shown that acute administration of theophylline can rescue phrenic nerve activity and diaphragmatic EMG on the side ipsilateral to injury. However, this effect is dependent on intact and uninjured pathways. In this study we utilized a cervical contusion injury model that more closely mimics the human condition. This injury model can determine the effectiveness of therapeutic interventions, in this case theophylline, on the isolated contused pathways of the spinal cord. Three weeks after a 150kD C3/4 unilateral contusion subjects received a 15mg/kg dose of theophylline prior to a contralateral C2 hemisection. Subjects that received theophylline were able to effectively utilize damaged pathways to breathe for up to 2min, while subjects treated with saline were unable to support ventilation. Through these experiments, we demonstrate that theophylline can make injured pathways that mediate breathing more effective and therefore, suggest a potential therapeutic role in the critical time points immediately after injury.