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Delayed manipulation of regeneration within injured peripheral axons.

Neurobiol Dis 2021 May 1:105383. Epub 2021 May 1.

Peripheral Nerve Research Laboratory, Division of Neurology, Department of Medicine and the Neurosciences and Mental Health Institute, University of Alberta, Canada. Electronic address:

While several new translational strategies to enhance regrowth of peripheral axons have been identified, combined approaches with different targets are rare. Moreover, few have been studied after a significant delay when growth programs are already well established and regeneration-related protein expression has waned. Here we study two approaches, Rb1 (Retinoblastoma 1) knockdown that targets overall neuron plasticity, and near nerve insulin acting as a growth factor. Read More

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Pembrolizumab-caused polyradiculoneuropathy as an immune-related adverse event.

Neuropathology 2021 May 3. Epub 2021 May 3.

Department of Neurology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan.

Immune-related adverse events (irAEs) commonly involve the gastrointestinal tract, endocrine glands, skin, and liver, and rarely the nervous system. The pathomechanism of irAEs in the nervous system is unclear, and so characterizing these severe toxic effects is a priority, even if irAEs are uncommon in the nervous system. Our patient presented subacute muscle weakness and dysesthesia with colitis as irAEs caused by pembrolizumab, one of the anti-programmed death-1 (PD-1) antibodies. Read More

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Long-term wireless streaming of neural recordings for circuit discovery and adaptive stimulation in individuals with Parkinson's disease.

Nat Biotechnol 2021 May 3. Epub 2021 May 3.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.

Neural recordings using invasive devices in humans can elucidate the circuits underlying brain disorders, but have so far been limited to short recordings from externalized brain leads in a hospital setting or from implanted sensing devices that provide only intermittent, brief streaming of time series data. Here, we report the use of an implantable two-way neural interface for wireless, multichannel streaming of field potentials in five individuals with Parkinson's disease (PD) for up to 15 months after implantation. Bilateral four-channel motor cortex and basal ganglia field potentials streamed at home for over 2,600 h were paired with behavioral data from wearable monitors for the neural decoding of states of inadequate or excessive movement. Read More

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Age-related iron accumulation and demyelination in the basal ganglia are closely related to verbal memory and executive functioning.

Sci Rep 2021 May 3;11(1):9438. Epub 2021 May 3.

Department of Psychology, University of Lübeck, 23562, Lübeck, Germany.

Age-related cognitive decline has been linked to alterations of the dopaminergic system and its subcortical trajectories. Recent work suggests a critical role of iron accumulation within the basal ganglia (BG) in verbal memory performance, and increased iron levels have been related to demyelination. However, the specificity of age-related iron increases with respect to cognitive functions remains unclear. Read More

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β2 adrenergic receptor mediates noradrenergic action to induce CREB phosphorylation in satellite glial cells of dorsal root ganglia to regulate visceral hypersensitivity.

Pain 2021 Apr 30. Epub 2021 Apr 30.

Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0551, USA.

Abstract: Sympathoneuronal outflow into dorsal root ganglia (DRG) is suggested to be involved in sympathetically maintained chronic pain, which is mediated by norepinephrine (NE) action on DRG cells. The present study combined in vitro and in vivo approaches to identify the cell types of DRG that received NE action and examined cell-type specific expression of adrenergic receptors (ARs) in DRG. Using DRG explants, we identified that NE acted on satellite glial cells (SGCs) to induce the phosphorylation of cAMP response element-binding (CREB). Read More

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Sympathectomy decreases pain behaviors and nerve regeneration by downregulating monocyte chemokine CCL2 in dorsal root ganglia in the rat tibial nerve crush model.

Pain 2021 Apr 30. Epub 2021 Apr 30.

Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, U.S.A. Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. *Present address.

Abstract: Peripheral nerve regeneration is associated with pain in several preclinical models of neuropathic pain. Some neuropathic pain conditions and preclinical neuropathic pain behaviors are improved by sympathetic blockade. In this study we examined the effect of a localized "microsympathectomy," i. Read More

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Therapeutic targeting of Lyn kinase to treat chorea-acanthocytosis.

Acta Neuropathol Commun 2021 May 3;9(1):81. Epub 2021 May 3.

Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Chorea-Acanthocytosis (ChAc) is a devastating, little understood, and currently untreatable neurodegenerative disease caused by VPS13A mutations. Based on our recent demonstration that accumulation of activated Lyn tyrosine kinase is a key pathophysiological event in human ChAc cells, we took advantage of Vps13a mice, which phenocopied human ChAc. Using proteomic approach, we found accumulation of active Lyn, γ-synuclein and phospho-tau proteins in Vps13a basal ganglia secondary to impaired autophagy leading to neuroinflammation. Read More

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The Ambibaric Brain: Pathophysiological and Clinical Implications.

Stroke 2021 May 4:STROKEAHA120033492. Epub 2021 May 4.

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (L.Ø.).

We propose a new evolutionary interpretation of the brain's circulation that has physiological, pathophysiological, and clinical implications. We review the evidence for the concept, discuss clinical implications, and suggest techniques to address outstanding questions. We conclude that the brain circulation contains complementary low-pressure and high-pressure system that must be kept in balance for optimal brain health. Read More

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cGMP signalling in dorsal root ganglia and the spinal cord: Various functions in development and adulthood.

Br J Pharmacol 2021 May 3. Epub 2021 May 3.

Institute of Pharmacology and Clinical Pharmacy, Goethe University, Frankfurt am Main, Germany.

Cyclic GMP (cGMP) is a second messenger that regulates numerous physiological and pathophysiological processes. In recent years, more and more studies have uncovered multiple roles of cGMP signalling pathways in the somatosensory system. Accumulating evidence suggests that cGMP regulates different cellular processes from embryonic development through adulthood. Read More

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Neural substrates of neuropsychological profiles in dystrophynopathies: A pilot study of diffusion tractography imaging.

PLoS One 2021 3;16(5):e0250420. Epub 2021 May 3.

Department of Developmental Neuroscience, IRCCS Stella Maris, Calambrone, Pisa, Italy.

Introduction: Cognitive difficulties and neuropsychological alterations in Duchenne and Becker muscular dystrophy (DMD, BMD) boys are not yet sufficiently explored, although this topic could have a relevant impact, finding novel biomarkers of disease both at genetics and neuroimaging point of view. The current study aims to: 1) analyze the neuropsychological profile of a group of DMD and BMD boys without cognitive impairment with an assessment of their executive functions; 2) explore the structural connectivity in DMD, BMD, and age-matched controls focusing on cortico-subcortical tracts that connect frontal cortex, basal ganglia, and cerebellum via the thalamus; 3) explore possible correlations between altered structural connectivity and clinical neuropsychological measures.

Materials And Methods: This pilot study included 15 boys (5 DMD subjects, 5 BMD subjects, and 5 age-matched typically developing, TD). Read More

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Emerging Disease-Modifying Therapies in Neurodegeneration With Brain Iron Accumulation (NBIA) Disorders.

Front Neurol 2021 15;12:629414. Epub 2021 Apr 15.

Department of Neurology With Friedrich Baur Institute, University Hospital of Ludwig-Maximilians-Universität München, Munich, Germany.

Neurodegeneration with Brain Iron Accumulation (NBIA) is a heterogeneous group of progressive neurodegenerative diseases characterized by iron deposition in the globus pallidus and the substantia nigra. As of today, 15 distinct monogenetic disease entities have been identified. The four most common forms are pantothenate kinase-associated neurodegeneration (PKAN), phospholipase A2 group VI (PLA2G6)-associated neurodegeneration (PLAN), beta-propeller protein-associated neurodegeneration (BPAN) and mitochondrial membrane protein-associated neurodegeneration (MPAN). Read More

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Rostral Intralaminar Thalamus Engagement in Cognition and Behavior.

Front Behav Neurosci 2021 15;15:652764. Epub 2021 Apr 15.

Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, United States.

The thalamic rostral intralaminar nuclei (rILN) are a contiguous band of neurons that include the central medial, paracentral, and central lateral nuclei. The rILN differ from both thalamic relay nuclei, such as the lateral geniculate nucleus, and caudal intralaminar nuclei, such as the parafascicular nucleus, in afferent and efferent connectivity as well as physiological and synaptic properties. rILN activity is associated with a range of neural functions and behaviors, including arousal, pain, executive function, and action control. Read More

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Dementia and Parkinson-like syndrome with basal ganglia lesion in neuromyelitis optica spectrum disorders.

Neurocase 2021 May 2:1-4. Epub 2021 May 2.

Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Brain lesions in neuromyelitis optica spectrum disorders (NMOSD) are generally located at sites of high anti-aquaporin 4 (AQP4) expression. Clinical features of NMOSD associated with basal ganglia damage in sites not enriched with AQP4 remain unknown. Here we describe the case of an 82-year-old woman who developed dementia and bradykinesia for 5 weeks. Read More

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Acupuncture modulates extracellular ATP levels in peripheral sensory nervous system during analgesia of ankle arthritis in rats.

Purinergic Signal 2021 May 2. Epub 2021 May 2.

School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China.

As an ancient analgesia therapy, acupuncture has been practiced worldwide nowadays. A good understanding of its mechanisms will offer a promise for its rational and wider application. As the first station of pain sensation, peripheral sensory ganglia express pain-related P2X receptors that are involved in the acupuncture analgesia mechanisms transduction pathway. Read More

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Pineal region tumours in thesitting position: how I do it.

Acta Neurochir (Wien) 2021 May 2. Epub 2021 May 2.

Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.

Background: Pineal region tumours remain challenging neurosurgical pathologies.

Methods: Detailed anatomical knowledge of the posterior incisural space and its variations is critical. An opaque arachnoidal membrane seals the internal cerebral and basal veins, leading to thalamic, basal ganglia, mesencephalic/pontine infarctions if injured. Read More

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Brain MRI after therapeutic hypothermia in asphyxiated newborns: Predictive value at one year of imaging features.

Eur J Radiol 2021 Apr 15;139:109724. Epub 2021 Apr 15.

Service d'imagerie anténatale, de l'enfant et de la femme, Hôpital Pellegrin, place Amélie Raba-Léon, F-33076, Bordeaux, France; CRMSB, UMR5536 CNRS/Univ. Bordeaux, F-33076, Bordeaux, France. Electronic address:

Purpose: To compare early brain MRI using a composite imaging score and outcome at one year in asphyxiated newborns treated by hypothermia.

Methods: This retrospective study included for two years consecutive asphyxiated term newborns treated by hypothermia for hypoxic-ischemic encephalopathy, and who had brain MRI before day 8. Therapeutic hypothermia was initiated within the first 6 h of life and continued for 72 h. Read More

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High intensity aerobic exercise improves bimanual coordination of grasping forces in Parkinson's disease.

Parkinsonism Relat Disord 2021 Apr 20;87:13-19. Epub 2021 Apr 20.

Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA; Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA. Electronic address:

Introduction: Parkinson's disease (PD) disrupts the control and coordination of grasping forces, likely due to a disruption in basal ganglia circuitry and diminished activity within the supplementary motor area (SMA). High intensity aerobic exercise has been shown to enhance connectivity between basal ganglia nuclei and cortical areas, including the SMA. The aim of this project was to determine the effects of high intensity lower extremity exercise on motor control patterns underlying a manual dexterity task. Read More

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[Involvement of Pirt /TRPV1 signaling in acupuncture-induced reduction of visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome rats].

Zhen Ci Yan Jiu 2021 Apr;46(4):278-83

School of Acupuncture-moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

Objective: To observe the effect of electroacupuncture (EA) on the expression of Pirt (a regulator of TRPV1) in the dorsal root ganglia (DRG) and transient receptor potential vanilloid 1 (TRPV1, a molecular sensor of noxious heat and capsaicin) in the colonic mucosa in rats suffering from diarrhea-predominant irritable bowel syndrome (IBS-D), so as to explore its mechanisms underlying alleviation of visceral hypersensitivity of IBS-D.

Methods: Forty SD rats (half male and half female) were randomly assigned to control, model, EA, and medication groups by lottery, with 10 rats in each group. The IBS-D model was established by chronic unpredictable mild stress (CUMS) and gavage of senna soaking fluid. Read More

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Input of Sensory, Limbic, Basal Ganglia and Pallial/Cortical Information into the Ventral/Lateral Habenula: Functional Principles in Anuran Amphibians.

Brain Res 2021 Apr 27:147506. Epub 2021 Apr 27.

Institute for Zoology, University of Cologne, Zülpicher Str. 47b, 50674 Cologne, Germany.

The habenula - a phylogenetically old brain structure present in all vertebrates - is involved in pain processing, reproductive behaviors, sleep-wake cycles, stress responses, reward, and learning. We performed intra- and extracellular recordings of ventral habenula (VHb) neurons in the isolated brain of anurans and revealed similar cell and response properties to those reported for the lateral habenula of mammals. We identified tonic regular, tonic irregular, rhythmic firing, and silent VHb neurons. Read More

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Intrinsic Cardiac Autonomic Nervous System: what do clinical electrophysiologists need to know about the 'heart brain'?

J Cardiovasc Electrophysiol 2021 Apr 29. Epub 2021 Apr 29.

Lithuanian University of Health Sciences, Kaunas, Lithuania.

It is increasingly recognized that the autonomic nervous system (ANS) is a major contributor in many cardiac arrhythmias. Cardiac ANS can be divided into extrinsic and intrinsic parts according to the course of nerve fibers and localization of ganglia and neuron bodies. Although the role of extrinsic part has historically gained more attention, the intrinsic cardiac ANS may affect cardiac function independently as well as influence the effects of the extrinsic nerves. Read More

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MR T1 mapping for quantifying brain manganese deposition in type C hepatic encephalopathy rats.

Biometals 2021 Apr 29. Epub 2021 Apr 29.

Department of Radiology, Jinshan Hospital of Fudan University, 1508 Longhang Road, Shanghai, 201508, China.

To evaluate magnetic resonance (MR) T1 mapping for quantifying brain manganese (Mn) deposition in type C hepatic encephalopathy (CHE) rats and to investigate the mechanism of magnesium sulfate (MgSO) therapy. Thirty Sprague-Dawley rats were randomly assigned into normal control group (NC, n = 6) and CHE groups (n = 24). Thioacetamide (TAA) was used for modeling CHE rats. Read More

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The effect of directional social cues on saccadic eye movements in Parkinson's disease.

Exp Brain Res 2021 Apr 29. Epub 2021 Apr 29.

School of Psychology, University of Lincoln, Lincoln, LN6 7TS, UK.

There is growing interest in how social processes and behaviour might be affected in Parkinson's disease. A task which has been widely used to assess how people orient attention in response to social cues is the spatial cueing task. Socially relevant directional cues, such as a picture of someone gazing or pointing to the left or the right have been shown to cause orienting of visual attention in the cued direction. Read More

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Lesions that do or do not impair digit span: a study of 816 stroke survivors.

Brain Commun 2021 10;3(2):fcab031. Epub 2021 Mar 10.

Wellcome Centre for Human Neuroimaging, University College London, London WC1N 3AR, UK.

Prior studies have reported inconsistency in the lesion sites associated with verbal short-term memory impairments. Here we asked: How many different lesion sites can account for selective impairments in verbal short-term memory that persist over time, and how consistently do these lesion sites impair verbal short-term memory? We assessed verbal short-term memory impairments using a forward digit span task from the Comprehensive Aphasia Test. First, we identified the incidence of digit span impairments in a sample of 816 stroke survivors (541 males/275 females; age at stroke onset 56 ± 13 years; time post-stroke 4. Read More

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Networks in the Field of Tourette Syndrome.

Front Neurol 2021 13;12:624858. Epub 2021 Apr 13.

Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany.

Gilles de la Tourette syndrome (TS) is a neuropsychiatric neurodevelopmental disorder with the cardinal clinical features of motor and phonic tics. Clinical phenomenology can be complex since, besides tics, there are other features including premonitory urges preceding tics, pali-, echo-, and coprophenomena, hypersensitivity to external stimuli, and symptom dependency on stress, attention, and other less well-defined factors. Also, the rate of comorbidities, particularly attention deficit hyperactivity disorder and obsessive-compulsive disorder, is high. Read More

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Carvedilol Exerts Neuroprotective Effect on Rat Model of Diabetic Neuropathy.

Front Pharmacol 2021 13;12:613634. Epub 2021 Apr 13.

Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

Diabetic neuropathy (DN) commonly occurs in diabetics, affecting approximately 50% of both type 1 and 2 diabetic patients. It is a leading cause of non-traumatic amputations. Oxidative stress could play a key role in the pathophysiology of DN. Read More

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Mechanism of White Matter Injury and Promising Therapeutic Strategies of MSCs After Intracerebral Hemorrhage.

Front Aging Neurosci 2021 13;13:632054. Epub 2021 Apr 13.

Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Intracerebral hemorrhage (ICH) is the most fatal subtype of stroke with high disability and high mortality rates, and there is no effective treatment. The predilection site of ICH is in the area of the basal ganglia and internal capsule (IC), where exist abundant white matter (WM) fiber tracts, such as the corticospinal tract (CST) in the IC. Proximal or distal white matter injury (WMI) caused by intracerebral parenchymal hemorrhage is closely associated with poor prognosis after ICH, especially motor and sensory dysfunction. Read More

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Volume of beta bursts, but not their rate, predicts successful response inhibition.

J Neurosci 2021 Apr 29. Epub 2021 Apr 29.

School of Psychology and Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland

In humans, impaired response inhibition is characteristic of a wide range of psychiatric diseases and of normal aging. It is hypothesised that the right inferior frontal cortex plays a key role by inhibiting the motor cortex via the basal ganglia. The electroencephalography-derived beta rhythm (15-29 Hz) is thought to reflect communication within this network, with increased right frontal beta power often observed prior to successful response inhibition. Read More

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The Human Basal Ganglia Mediate the Interplay between Reactive and Proactive Control of Response through Both Motor Inhibition and Sensory Modulation.

Brain Sci 2021 Apr 28;11(5). Epub 2021 Apr 28.

Université de Lyon, 69622 Lyon, France.

The basal ganglia (BG) have long been known for contributing to the regulation of motor behaviour by means of a complex interplay between tonic and phasic inhibitory mechanisms. However, after having focused for a long time on phasic reactive mechanisms, it is only recently that psychological research in healthy humans has modelled tonic proactive mechanisms of control. Mutual calibration between anatomo-functional and psychological models is still needed to better understand the unclear role of the BG in the interplay between proactive and reactive mechanisms of control. Read More

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BK Channel Inhibition by Peripheral Nerve Injury Is Restored by the Xanthine Derivative KMUP-1 in Dorsal Root Ganglia.

Cells 2021 Apr 20;10(4). Epub 2021 Apr 20.

Department of Pharmacology, Graduate Institute of Medicine, College of Medicine, Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

This study explored whether KMUP-1 improved chronic constriction injury (CCI)-induced BK current inhibition in dorsal root ganglion (DRG) neurons. Rats were randomly assigned to four groups: sham, sham + KMUP-1, CCI, and CCI + KMUP-1 (5 mg/kg/day, i.p. Read More

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Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates.

Cells 2021 Apr 16;10(4). Epub 2021 Apr 16.

Child Study Center, Yale University, New Haven, CT 06520, USA.

The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease. The classic animal models and monolayer in vitro systems have limited the types of questions scientists can strive to answer in addition to the technical ability to answer them. However, the tridimensional human stem cell-derived organoid system provides the unique opportunity to model human development and mimic the diverse cellular composition of human organs. Read More

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