1,721,010 research outputs found
Past, Present, and Future of Neuronal Models In Vitro
No full textOver the past century, robust methods were developed that enable the isolation, culture, and dynamic observation of mammalian neuronal networks in vitro. But even if neuronal culture cannot yet fully recapitulate the normal brain, the knowledge that has been acquired from these surrogate in vitro models is invaluable. Indeed, neuronal culture has continued to propel basic neuroscience research, proving that in vitro systems have legitimacy when it comes to studying either the healthy or diseased human brain. Furthermore, scientific advancement typically parallels technical refinements in the field. A pertinent example is that a collective drive in the field of neuroscience to better understand the development, organization, and emergent properties of neuronal networks is being facilitated by progressive advances in micro-electrode array (MEA) technology. In this chapter, we briefly review the emergence of neuronal cell culture as a technique, the current trends in human stem cell-based modeling, and the technologies used to monitor neuronal communication. We conclude by highlighting future prospects that are evolving specifically out of the combination of human neuronal models and MEA technology.</p
Network dynamics of 3D engineered neuronal cultures: a new experimental model for in-vitro electrophysiology
No full textInterfacing 3D engineered neuronal cultures to micro-electrode arrays: An innovative in vitro experimental model
No full textThe potential of in vitro neuronal networks cultured on micro electrode arrays for biomedical research
Full text linkIn vitro neuronal models have become an important tool to study healthy and diseased neuronal circuits. The growing interest of neuroscientists to explore the dynamics of neuronal systems and the increasing need to observe, measure and manipulate not only single neurons but populations of cells pushed for technological advancement. In this sense, micro-electrode arrays (MEAs) emerged as a promising technique, made of cell culture dishes with embedded micro-electrodes allowing non-invasive and relatively simple measurement of the activity of neuronal cultures at the network level. In the past decade, MEAs popularity has rapidly grown. MEA devices have been extensively used to measure the activity of neuronal cultures mainly derived from rodents. Rodent neuronal cultures on MEAs have been employed to investigate physiological mechanisms, study the effect of chemicals in neurotoxicity screenings, and model the electrophysiological phenotype of neuronal networks in different pathological conditions. With the advancements in human induced pluripotent stem cells (hiPSCs) technology, the differentiation of human neurons from the cells of adult donors became possible. hiPSCs-derived neuronal networks on MEAs have been employed to develop patient-specific in vitro platforms to characterize the pathophysiological phenotype and to test drugs, paving the way towards personalized medicine. In this review, we first describe MEA technology and the information that can be obtained from MEA recordings. Then, we give an overview of studies in which MEAs have been used in combination with different neuronal systems (i.e. rodent 2D and three-dimensional (3D) neuronal cultures, organotypic brain slices, hiPSCs-derived 2D and 3D neuronal cultures, and brain organoids) for biomedical research, including physiology studies, neurotoxicity screenings, disease modeling, and drug testing. We end by discussing potential, challenges and future perspectives of MEA technology, and providing some guidance for the choice of the neuronal model and MEA device, experimental design, data analysis and reporting for scientific publications.</p
Neuroprotective role of lactate in a human in vitro model of the ischemic penumbra
Full text linkIn patients suffering from cerebral ischemic stroke, there is an urgent need for treatments to protect stressed yet viable brain cells. Recently, treatment strategies that induce neuronal activity have been shown to be neuroprotective. Here, we hypothesized that neuronal activation might maintain or trigger the astrocyte-to-neuron lactate shuttle (ANLS), whereby lactate is released from astrocytes to support the energy requirements of ATP-starved hypoxic neurons, and this leads to the observed neuroprotection. We tested this by using a human cell based in vitro model of the ischemic penumbra and investigating whether lactate might be neuroprotective in this setting. We found that lactate transporters are involved in the neuroprotective effect mediated by neuronal activation. Furthermore, we showed that lactate exogenously administered before hypoxia correlated with neuroprotection in our cellular model. In addition, stimulation of astrocyte with consequent endogenous production of lactate resulted in neuroprotection. To conclude, here we presented evidence that lactate transport into neurons contributes to neuroprotection during hypoxia providing a potential basis for therapeutic approaches in ischemic stroke.</p
PRELIMINAR ANALYSIS OF ENGINEERED FUNCTIONALLY ACTIVE HUMAN DERIVED CORTICAL NEUROSPHEROIDS FOR DRUG SCREENING AND PRECISION MEDICINE
No full textThe continue development of differentiation protocols to generate human neural cells in vitro, allows more accurate investigations of the functional mechanisms arising in such complex networks, and generates great expectations for new treatments in neurodegenerative diseases for which effective therapies are not yet available. The use of 3D aggregates for neuropharmacological in vitro studies has shown great potentials and the advent of human patient specific in vitro models opens new avenues in the field of drug screening and precision medicine. Moreover, Neuronal Stem Cell (NSC) transplantation has the potential to revolutionize brain disease research, but still presents limitations that hamper the use in therapeutics. It has been shown how the injection of NSCs directly into the host, leads to a random integration into the tissue, while a targeted transplant is needed in the specific area affected by degeneration. An alternative approach would be to produce an already differentiated healthy 3D tissue, that shows all the functional and morphological features suitable for transplant into the degenerated area. To this end, we optimized a fast differentiation protocol to engineer excitatory cortical neurospheres with 1:1 ratio between neurons and astrocytes. We first evaluated its morphology by imaging and then we evaluated its functionality (i.e. electrophysiological activity) with glassbased 60 and CMOS-based 4096 micro-electrode arrays (MEAs). Our preliminary results show how the generated structures are viable and functionally active throughout their development. Furthermore, CMOS-MEAs revealed network properties that did not emerge from standard MEAs. Although the obtained results are preliminary, all neurospheroids adhered to substrates and developed functionally active neuritic arborizations, suggesting their efficient use for functional drugs screening applications and for future in vivo transplantation
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Neuronal Responses to Ischemia: Scoping Review of Insights from Human-Derived In Vitro Models
Full text linkTranslation of neuroprotective treatment effects from experimental animal models to patients with cerebral ischemia has been challenging. Since pathophysiological processes may vary across species, an experimental model to clarify human-specific neuronal pathomechanisms may help. We conducted a scoping review of the literature on human neuronal in vitro models that have been used to study neuronal responses to ischemia or hypoxia, the parts of the pathophysiological cascade that have been investigated in those models, and evidence on effects of interventions. We included 147 studies on four different human neuronal models. The majority of the studies (132/147) was conducted in SH-SY5Y cells, which is a cancerous cell line derived from a single neuroblastoma patient. Of these, 119/132 used undifferentiated SH-SY5Y cells, that lack many neuronal characteristics. Two studies used healthy human induced pluripotent stem cell derived neuronal networks. Most studies used microscopic measures and established hypoxia induced cell death, oxidative stress, or inflammation. Only one study investigated the effect of hypoxia on neuronal network functionality using micro-electrode arrays. Treatment targets included oxidative stress, inflammation, cell death, and neuronal network stimulation. We discuss (dis)advantages of the various model systems and propose future perspectives for research into human neuronal responses to ischemia or hypoxia. Graphical Abstract: [Figure not available: see fulltext.].</p
- …
