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Midbrain

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121. Immature Midbrain Dopaminergic Neurons Derived from Floor‐Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease Full Text available with Trip Pro

Immature Midbrain Dopaminergic Neurons Derived from Floor‐Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease Recent reports have indicated human embryonic stem cells-derived midbrain dopamine (mDA) neurons as proper cell resources for use in Parkinson's disease (PD) therapy. Nevertheless, no detailed and systematic study has been conducted to identify which differentiation stages of mDA cells are most suitable for transplantation in PD therapy. Here, we

2017 Stem cells translational medicine

122. Space specific deficits in visual orientation discrimination caused by lesions in the midbrain stimulus selection network Full Text available with Trip Pro

Space specific deficits in visual orientation discrimination caused by lesions in the midbrain stimulus selection network Perceptual decisions require both analysis of sensory information and selective routing of relevant information to decision networks. This study explores the contribution of a midbrain network to visual perception in chickens. Analysis of visual orientation information in birds takes place in the forebrain sensory area called the Wulst, as it does in the primary visual (...) cortex (V1) of mammals. In contrast, the midbrain, which receives parallel retinal input, encodes orientation poorly, if at all. We discovered, however, that small electrolytic lesions in the midbrain severely impair a chicken's ability to discriminate orientations. Focal lesions were placed in the optic tectum (OT) and in the nucleus isthmi pars parvocellularis (Ipc)-key nodes in the midbrain stimulus selection network-in chickens trained to perform an orientation discrimination task. A lesion

2017 Current biology : CB

123. Ischemic Stroke of Midbrain and Cerebellum Involving Reticular Activating System Full Text available with Trip Pro

Ischemic Stroke of Midbrain and Cerebellum Involving Reticular Activating System The reticular activating system is the part of the brain that maintains the sleep/wake cycle. Any damage to this region can cause hypersomnolence and drowsiness along with altered sensorium. This case presents a patient with cerebellar and midbrain stroke with infarct of the reticular activating system, leading to hypersomnolence, drowsiness, and altered sensorium.

2017 Cureus

124. OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH ALTERED MIDBRAIN CHEMICAL CONCENTRATIONS Full Text available with Trip Pro

OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH ALTERED MIDBRAIN CHEMICAL CONCENTRATIONS Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic (...) resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age±SD:54.6±10.6years; AHI:35.0±19.4; SAO2 min:83±7%) and 26 healthy control (50.7±8.5years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting

2017 Neuroscience

125. LOSS OF HYPERDIRECT PATHWAY CORTICO-SUBTHALAMIC INPUTS FOLLOWING DEGENERATION OF MIDBRAIN DOPAMINE NEURONS Full Text available with Trip Pro

LOSS OF HYPERDIRECT PATHWAY CORTICO-SUBTHALAMIC INPUTS FOLLOWING DEGENERATION OF MIDBRAIN DOPAMINE NEURONS The motor symptoms of Parkinson's disease (PD) are linked to abnormally correlated and coherent activity in the cortex and subthalamic nucleus (STN). However, in parkinsonian mice we found that cortico-STN transmission strength had diminished by 50%-75% through loss of axo-dendritic and axo-spinous synapses, was incapable of long-term potentiation, and less effectively patterned STN

2017 Neuron

126. Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease Full Text available with Trip Pro

Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease Cultured neural stem/precursor cells (NSCs) are regarded as a potential systematic cell source to treat Parkinson's disease (PD). However, the therapeutic potential of these cultured NSCs is lost during culturing. Here, we show that treatment of vitamin C (VC) enhances generation of authentic midbrain-type dopamine (mDA) neurons with improved (...) survival and functions from ventral midbrain (VM)-derived NSCs. VC acted by upregulating a series of mDA neuron-specific developmental and phenotype genes via removal of DNA methylation and repressive histone code (H3K9m3, H3K27m3) at associated gene promoter regions. Notably, the epigenetic changes induced by transient VC treatment were sustained long after VC withdrawal. Accordingly, transplantation of VC-treated NSCs resulted in improved behavioral restoration, along with enriched DA neuron

2017 Stem cell reports

127. In vitro generation of mature midbrain-type dopamine neurons by adjusting exogenous Nurr1 and Foxa2 expressions to their physiologic patterns Full Text available with Trip Pro

In vitro generation of mature midbrain-type dopamine neurons by adjusting exogenous Nurr1 and Foxa2 expressions to their physiologic patterns Developmental information aids stem cell biologists in producing tissue-specific cells. Recapitulation of the developmental profile of a specific cell type in an in vitro stem cell system provides a strategy for manipulating cell-fate choice during the differentiation process. Nurr1 and Foxa2 are potential candidates for genetic engineering to generate (...) midbrain-type dopamine (DA) neurons for experimental and therapeutic applications in Parkinson's disease (PD), as forced expression of these genes in neural stem/precursor cells (NPCs) yields cells with a complete battery of midbrain DA neuron-specific genes. However, simple overexpression without considering their expression pattern in the developing midbrain tends to generate DA cells without adequate neuronal maturation and long-term maintenance of their phenotype in vitro and in vivo after

2017 Experimental & molecular medicine

128. Segregated fronto‐cortical and midbrain connections in the mouse and their relation to approach and avoidance orienting behaviors Full Text available with Trip Pro

Segregated fronto‐cortical and midbrain connections in the mouse and their relation to approach and avoidance orienting behaviors The orchestration of orienting behaviors requires the interaction of many cortical and subcortical areas, for example the superior colliculus (SC), as well as prefrontal areas responsible for top-down control. Orienting involves different behaviors, such as approach and avoidance. In the rat, these behaviors are at least partially mapped onto different SC

2017 The Journal of comparative neurology

129. A High-fat Diet Induces a Loss of Midbrain Dopaminergic Neuronal Function That Underlies Motor Abnormalities Full Text available with Trip Pro

A High-fat Diet Induces a Loss of Midbrain Dopaminergic Neuronal Function That Underlies Motor Abnormalities Movement defects in obesity are associated with peripheral muscle defects, arthritis, and dysfunction of motor control by the brain. Although movement functionality is negatively correlated with obesity, the brain regions and downstream signaling pathways associated with movement defects in obesity are unclear. A dopaminergic neuronal pathway from the substantia nigra (SN

2017 Experimental neurobiology

130. Roundabout receptor 2 maintains inhibitory control of the adult midbrain Full Text available with Trip Pro

Roundabout receptor 2 maintains inhibitory control of the adult midbrain The maintenance of excitatory and inhibitory balance in the brain is essential for its function. Here we find that the developmental axon guidance receptor Roundabout 2 (Robo2) is critical for the maintenance of inhibitory synapses in the adult ventral tegmental area (VTA), a brain region important for the production of the neurotransmitter dopamine. Following selective genetic inactivation of Robo2 in the adult VTA

2017 eLife

131. Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells Full Text available with Trip Pro

Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells Research on human brain development and neurological diseases is limited by the lack of advanced experimental in vitro models that truly recapitulate the complexity of the human brain. Here, we describe a robust human brain organoid system that is highly specific to the midbrain derived from regionally patterned neuroepithelial stem cells. These human midbrain organoids contain spatially organized groups (...) of dopaminergic neurons, which make them an attractive model for the study of Parkinson's disease. Midbrain organoids are characterized in detail for neuronal, astroglial, and oligodendrocyte differentiation. Furthermore, we show the presence of synaptic connections and electrophysiological activity. The complexity of this model is further highlighted by the myelination of neurites. The present midbrain organoid system has the potential to be used for advanced in vitro disease modeling and therapy

2017 Stem cell reports

132. Gene Expression Profiling with Cre-Conditional Pseudorabies Virus Reveals a Subset of Midbrain Neurons That Participate in Reward Circuitry Full Text available with Trip Pro

Gene Expression Profiling with Cre-Conditional Pseudorabies Virus Reveals a Subset of Midbrain Neurons That Participate in Reward Circuitry The mesolimbic dopamine pathway receives inputs from numerous regions of the brain as part of a neural system that detects rewarding stimuli and coordinates a behavioral response. The capacity to simultaneously map and molecularly define the components of this complex multisynaptic circuit would thus advance our understanding of the determinants

2017 The Journal of Neuroscience

133. Hierarchical prediction errors in midbrain and septum during social learning Full Text available with Trip Pro

Hierarchical prediction errors in midbrain and septum during social learning Social learning is fundamental to human interactions, yet its computational and physiological mechanisms are not well understood. One prominent open question concerns the role of neuromodulatory transmitters. We combined fMRI, computational modelling and genetics to address this question in two separate samples (N = 35, N = 47). Participants played a game requiring inference on an adviser's intentions whose motivation (...) to help or mislead changed over time. Our analyses suggest that hierarchically structured belief updates about current advice validity and the adviser's trustworthiness, respectively, depend on different neuromodulatory systems. Low-level prediction errors (PEs) about advice accuracy not only activated regions known to support 'theory of mind', but also the dopaminergic midbrain. Furthermore, PE responses in ventral striatum were influenced by the Met/Val polymorphism of the Catechol-O

2017 Social cognitive and affective neuroscience

134. Reward Dependent Invigoration Relates to Theta Oscillations and Is Predicted by Dopaminergic Midbrain Integrity in Healthy Elderly Full Text available with Trip Pro

Reward Dependent Invigoration Relates to Theta Oscillations and Is Predicted by Dopaminergic Midbrain Integrity in Healthy Elderly Motivation can have invigorating effects on behavior via dopaminergic neuromodulation. While this relationship has mainly been established in theoretical models and studies in younger subjects, the impact of structural declines of the dopaminergic system during healthy aging remains unclear. To investigate this issue, we used electroencephalography (EEG) in healthy

2017 Frontiers in aging neuroscience

135. Efficient generation of hPSC-derived midbrain dopaminergic neurons in a fully defined, scalable, 3D biomaterial platform Full Text available with Trip Pro

Efficient generation of hPSC-derived midbrain dopaminergic neurons in a fully defined, scalable, 3D biomaterial platform Pluripotent stem cells (PSCs) have major potential as an unlimited source of functional cells for many biomedical applications; however, the development of cell manufacturing systems to enable this promise faces many challenges. For example, there have been major recent advances in the generation of midbrain dopaminergic (mDA) neurons from stem cells for Parkinson's Disease

2017 Scientific reports

136. Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain Full Text available with Trip Pro

Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified (...) consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes. Gene expression of 12 dopamine-related molecules was examined in post-mortem midbrain (28 antipsychotic-treated schizophrenia cases/29 controls) using quantitative PCR. TH and the synaptic dopamine transporter (DAT) proteins were examined in post-mortem midbrain (26 antipsychotic-treated schizophrenia cases per

2017 Translational psychiatry

137. Dopamine Induces Oscillatory Activities in Human Midbrain Neurons with Parkin Mutations Full Text available with Trip Pro

Dopamine Induces Oscillatory Activities in Human Midbrain Neurons with Parkin Mutations Locomotor symptoms in Parkinson's disease (PD) are accompanied by widespread oscillatory neuronal activities in basal ganglia. Here, we show that activation of dopamine D1-class receptors elicits a large rhythmic bursting of spontaneous excitatory postsynaptic currents (sEPSCs) in midbrain neurons differentiated from induced pluripotent stem cells (iPSCs) of PD patients with parkin mutations, but not normal (...) in patient-specific iPSC-derived midbrain neurons provides a mechanistic clue to PD pathophysiology, and it demonstrates the usefulness of this model system in understanding how mutations of parkin cause movement symptoms in Parkinson's disease.Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

2017 Cell reports

138. Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation Full Text available with Trip Pro

Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures. Rho guanine nucleotide exchange factor (ARHGEF) family members are key for controlling the spatiotemporal activation of Rho GTPase, to modulate cytoskeleton dynamics, cell division, and cell migration. We identified, by means (...) of whole exome sequencing, a homozygous frameshift mutation in the ARHGEF2 as a cause of intellectual disability, a midbrain-hindbrain malformation, and mild microcephaly in a consanguineous pedigree of Kurdish-Turkish descent. We show that loss of ARHGEF2 perturbs progenitor cell differentiation and that this is associated with a shift of mitotic spindle plane orientation, putatively favoring more symmetric divisions. The ARHGEF2 mutation leads to reduction in the activation of the RhoA/ROCK/MLC

2017 PLoS genetics

139. Long-Term Impairment of Sound Processing in the Auditory Midbrain by Daily Short-Term Exposure to Moderate Noise Full Text available with Trip Pro

Long-Term Impairment of Sound Processing in the Auditory Midbrain by Daily Short-Term Exposure to Moderate Noise Most citizen people are exposed daily to environmental noise at moderate levels with a short duration. The aim of the present study was to determine the effects of daily short-term exposure to moderate noise on sound level processing in the auditory midbrain. Sound processing properties of auditory midbrain neurons were recorded in anesthetized mice exposed to moderate noise (80 dB (...) a 12-week period of recovery in a quiet laboratory environment after completion of noise exposure. In conclusion, even daily short-term exposure to moderate noise can cause long-term impairment of sound level processing in a frequency-specific manner in auditory midbrain neurons.

2017 Neural plasticity

140. A rare case of Bruns syndrome with bilateral superior oblique palsy and dorsal midbrain syndrome. (Abstract)

A rare case of Bruns syndrome with bilateral superior oblique palsy and dorsal midbrain syndrome. We report a case of an 11-year-old boy referred for evaluation of esotropia associated with a 4-year history of intermittent headaches and vomiting triggered by sudden movements, such as sneezing and coughing. Magnetic resonance imaging (MRI) performed 3 years previously was reported to be normal. A thorough clinical examination revealed the clinical features of Dorsal midbrain syndrome with Bruns

2017 JAAPOS - Journal of the American Association for Pediatric Ophthalmology and Strabismus

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