Neural therapy

Malignant gliomas are the most common, infiltrative, and lethal primary brain tumors affecting the adult population. The grim prognosis for this disease is due to a combination of the presence of highly invasive tumor cells that escape surgical resection and the presence of a population of therapy-resistant cancer stem cells found within these tumors. Several studies suggest that glioma cells have cleverly hijacked the normal developmental program of neural progenitor cells, including their transcriptional programs, to enhance gliomagenesis...

Diffusion-weighted imaging (DWI) is used to measure gray matter tissue density and white matter fiber organization/directionality. Recent studies show that DWI also allows for assessing neuroplastic adaptations in the human hypothalamus. To this end, we investigated a potential influence of testosterone replacement therapy on hypothalamic microstructure in female-to-male (FtM) transgender individuals. 25 FtMs were measured at baseline, 4 weeks, and 4 months past treatment start and compared to 25 female and male controls...

BACKGROUND: Nephroblastoma and neuroblastoma belong to the most common abdominal malignancies in childhood. Similarities in the initial presentation may provide difficulties in distinguishing between these two entities, especially if unusual variations to prevalent patterns of disease manifestation occur. Because of the risk of tumor rupture, European protocols do not require biopsy for diagnosis, which leads to misdiagnosis in some cases. CASE PRESENTATION: We report on a 4½-year-old girl with a renal tumor displaying radiological and laboratory characteristics supporting the diagnosis of nephroblastoma...

SIGNIFICANCE: Numerous studies have demonstrated the actions of reactive oxygen species (ROS) as regulators of several physiological processes. Here we discuss how the redox signaling mechanisms operate to control different processes such as neuronal differentiation, oligodendrocyte differentiation, dendritic growth, and axonal growth. Recent Advances: Redox homeostasis regulates the physiology of neural stem cells (NSCs). Notably, the neuronal differentiation process of NSCs is determined by a change towards an oxidative metabolism, increased levels of mitochondrial ROS, increased activity of NOX enzymes, decreased levels of Nrf2, and a differential regulation of different redoxins...

INTRODUCTION: Vitamin B3 has been shown to play an important role during embryogenesis. Specifically, there is growing evidence that nicotinamide, the biologically active form of vitamin B3, plays a critical role as a morphogen in the differentiation of stem cells to mature cell phenotypes, including those of the central nervous system (CNS). Detailed knowledge of the action of small molecules during neuronal differentiation is not only critical for uncovering mechanisms underlying lineage-specification, but also to establish more effective differentiation protocols to obtain clinically relevant cells for regenerative therapies for neurodegenerative conditions such as Huntington's disease (HD)...

Acute central nervous system (CNS) injury, encompassing traumatic brain injury (TBI) and stroke, accounts for a significant burden of morbidity and mortality worldwide, largely attributable to the development of cerebral oedema and elevated intracranial pressure (ICP). Despite this, clinical treatments are limited and new therapies are urgently required to improve patient outcomes and survival. Originally characterised in peripheral tissues, such as the skin and lungs as a neurally-elicited inflammatory process that contributes to increased microvascular permeability and tissue swelling, neurogenic inflammation has now been described in acute injury to the brain where it may play a key role in the secondary injury cascades that evolve following both TBI and stroke...

BACKGROUND: Baroreflex activation therapy (BAT) exerts in severe heart failure sympathoinhibitory effects, improving clinical variables and reducing hospitalization rate. The current follow-up study was aimed at determining the long-term effects of BAT, assessing whether BAT in heart failure allows to restore physiological levels of sympathetic function. METHODS: Seven patients out of the 11 heart failure patients aged 66.5 ± 3 years (mean ± SEM) in New York Heart Association Class III with left ventricular ejection fraction 40% or less and impaired functional capacity recruited in the study survived at the final follow-up (43...

Robot-assisted training is a widely used technique to promote motor re-learning on post-stroke patients that suffer from motor impairment. While it is commonly accepted that robot-based therapies are potentially helpful, strong insights about their efficacy are still lacking. The motor re-learning process may act on muscular synergies, which are groups of co-activating muscles that, being controlled as a synergic group, allow simplifying the problem of motor control. In fact, by coordinating a reduced amount of neural signals, complex motor patterns can be elicited...

About a quarter of stroke patients worldwide suffer serious language disorders such as aphasias. Most common symptoms of Broca's aphasia are word naming disorders which highly impact verbal communication and the quality of life of aphasic patients. In order to recover disturbances in word retrieval, several cueing methods (i.e. phonemic and semantic) have been established to improve lexical access establishing effective language rehabilitation techniques. Based on recent evidence from action-perception theories, which postulate that neural circuits for speech perception and articulation are tightly coupled, in the present work, we propose and investigate an alternative type of cueing using silent articulation-related visual stimuli...

This paper presents the preliminary findings of a multi-year clinical study evaluating the effectiveness of adding a brain-machine interface (BMI) to the MAHI-Exo II, a robotic upper limb exoskeleton, for elbow flexion/extension rehabilitation in chronic stroke survivors. The BMI was used to trigger robot motion when movement intention was detected from subjects' neural signals, thus requiring that subjects be mentally engaged during robotic therapy. The first six subjects to complete the program have shown improvements in both Fugl-Meyer Upper-Extremity scores as well as in kinematic movement quality measures that relate to movement planning, coordination, and control...

In the developing brain, neurons expressing VEGF-A and blood vessels grow in close apposition, but many of the molecular pathways regulating neuronal VEGF-A and neurovascular system development remain to be deciphered. Here, we show that miR-9 links neurogenesis and angiogenesis through the formation of neurons expressing VEGF-A. We found that miR-9 directly targets the transcription factors TLX and ONECUTs to regulate VEGF-A expression. miR-9 inhibition leads to increased TLX and ONECUT expression, resulting in VEGF-A overexpression...

The development of cell-based therapies using stem cells represents a significant breakthrough in the treatment of limbal stem cell deficiency (LSCD). The aim of this study was to develop a novel protocol to differentiate human embryonic stem cells (hESCs) into corneal epithelial progenitor cells (CEPCs), with similar features to primary cultured human limbal stem cells (LSCs), using a medium composed of DMEM/F12 and defined keratinocyte serum-free medium (KSFM) (1:1) under different carbon dioxide (CO2) levels in culture...

Deep brain stimulation (DBS) has become a widely used technique for treating advanced stages of neurological and psychiatric illness. In the case of motor disorders related to basal ganglia (BG) dysfunction, several mechanisms of action for the DBS therapy have been identified which might be involved simultaneously or in sequence. However, the identification of a common key mechanism underlying the clinical relevant DBS configurations has remained elusive due to the inherent complexity related to the interaction between the electrical stimulation and the neural tissue, and the intricate circuital structure of the BG-thalamocortical network...

BACKGROUND AND PURPOSE: Tissue plasminogen activator (tPA) is the only approved pharmacological therapy for acute brain ischemia; however, a major limitation of tPA is the haemorrhagic transformation followed by tPA treatment. Here, we determine whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, would affect tPA-induced haemorrhagic transformation. EXPERIMENTAL APPROACH: Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 hours...

BACKGROUND AND PURPOSE: To implement a robust and fast stereotactic MR-guided adaptive radiation therapy (SMART) online strategy in locally advanced pancreatic cancer (LAPC). MATERIAL AND METHODS: SMART strategy for plan adaptation was implemented with the MRIdian system (ViewRay Inc.). At each fraction, OAR (re-)contouring is done within a distance of 3cm from the PTV surface. Online plan re-optimization is based on robust prediction of OAR dose and optimization objectives, obtained by building an artificial neural network (ANN)...

Devising efficient gene delivery systems is crucial to enhancing the therapeutic efficacy of gene-cell therapy approaches. Herein, inverted quasi-spherical (iQS) droplet systems, which enhance gene delivery efficiencies by reducing the path lengths of gene vectors, mediating motions of vectors at early stages, and raising the contact frequencies of vectors with cells, are developed by adopting the principle of 3D hanging-drop cell culture. Micrometer-sized polydopamine (pDA) holes are created on superhydrophobic titanium isopropoxide (TiO2 )-coated substrates by physical scraping; droplets are loaded on the pDA holes, and inversion of the substrate generates iQS droplets with large contact angles...

Adult neurogenesis mainly occurs at the subventricular zone (SVZ) on the walls of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG). However, the majority of newborn neurons undergo programmed cell death (PCD) during the period of proliferation, migration, and integration. Stroke activates neural stem cells (NSCs) in both SVZ and SGZ. This process is regulated by a wide variety of signaling pathways. However, the newborn neurons derived from adult neurogenesis are insufficient for tissue repair and function recovery...

Adult neurogenesis plays the important roles in animal cognitive and emotional behaviors. Abnormal proliferation and differentiation of neural stem cells (NSCs) usually associate with the neural dysfunctions induced by different brain disorders. Therefore, targeting neurogenic factors could be a promoting strategy for neural regeneration and brain repair. Importantly, epidemiological studies suggest metabolism disorders like diabetes and obesity significantly increase the risk of neurological and psychiatric diseases...

Re-formation or preservation of functional, electrically active neural networks has been proffered as one of the goals of stem cell-mediated neural therapeutics. A primary issue for a cell therapy approach is the formation of functional contacts between the implanted cells and the host tissue. Therefore, it is of fundamental interest to establish protocols that allow us to delineate a detailed time course of grafted stem cell survival, migration, differentiation, integration, and functional interaction with the host...

Spinal cord ischemia and reperfusion (SCIR) injury is the major cause of a wide range of complications, including neural degeneration and devastating paraplegia. Decrease of inhibitory neurotransmitters and increase of excitory neurotransmitters are the major cause for the excitotoxicity of neurons. However, no study has reported the temporal loss of motor neuron in the ventral horn of spinal cord area following SCIR-induced spastic paralysis, not even the mechanism under it. In the present study, we found that the rabbits were mainly spastic paralyzed after spinal cord ischemia-reperfusion injury...