Driving Oscillatory Dynamics: Neuromodulation for Recovery After Stroke

Stroke is a leading cause of death and disability worldwide, with limited treatments being available. However, advances in optic methods in neuroscience are providing new insights into the damaged brain and potential avenues for recovery. Direct brain stimulation has revealed close associations between mental states and neuroprotective processes in health and disease, and activity-dependent calcium indicators are being used to decode brain dynamics to understand the mechanisms underlying these associations. Evoked neural oscillations have recently shown the ability to restore and maintain intrinsic homeostatic processes in the brain and could be rapidly deployed during emergency care or shortly after admission into the clinic, making them a promising, non-invasive therapeutic option. We present an overview of the most relevant descriptions of brain injury after stroke, with a focus on disruptions to neural oscillations. We discuss the optical technologies that are currently used and lay out a roadmap for future studies needed to inform the next generation of strategies to promote functional recovery after stroke.

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Multi-disciplinary Approach for Drug and Gene Delivery Systems to the Brain

AAPS PharmSciTech ◽

10.1208/s12249-021-02144-1 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Nkafu Bechem Ndemazie ◽

Andriana Inkoom ◽

Ellis Fualefeh Morfaw ◽

Taylor Smith ◽

Monica Aghimien ◽

...

Keyword(s):

Drug Delivery ◽

Cerebrovascular Diseases ◽

Delivery Systems ◽

Great Resistance ◽

New Techniques ◽

Non Invasive ◽

Brain Drug Delivery ◽

Health And Disease ◽

Invasive Techniques ◽

The Brain

Abstract Drug delivery into the brain has for long been a huge challenge as the blood–brain barrier (BBB) offers great resistance to entry of foreign substances (with drugs inclusive) into the brain. This barrier in healthy individuals is protective to the brain, disallowing noxious substances present in the blood to get to the brain while allowing for the exchange of small molecules into the brain by diffusion. However, BBB is disrupted under certain disease conditions, such as cerebrovascular diseases including acute ischemic stroke and intracerebral hemorrhage, and neurodegenerative disorders including multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and cancers. This review aims to provide a broad overview of present-day strategies for brain drug delivery, emphasizing novel delivery systems. Hopefully, this review would inspire scientists and researchers in the field of drug delivery across BBB to uncover new techniques and strategies to optimize drug delivery to the brain. Considering the anatomy, physiology, and pathophysiological functioning of the BBB in health and disease conditions, this review is focused on the controversies drawn from conclusions of recently published studies on issues such as the penetrability of nanoparticles into the brain, and whether active targeted drug delivery into the brain could be achieved with the use of nanoparticles. We also extended the review to cover novel non-nanoparticle strategies such as using viral and peptide vectors and other non-invasive techniques to enhance brain uptake of drugs. Graphical abstract

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Electric Field Dynamics in the Brain During Multi-Electrode Transcranial Electric Stimulation

10.1101/340224 ◽

2018 ◽

Cited By ~ 4

Author(s):

Ivan Alekseichuk ◽

Arnaud Y. Falchier ◽

Gary Linn ◽

Ting Xu ◽

Michael P. Milham ◽

...

Keyword(s):

Electric Field ◽

Electric Stimulation ◽

Brain Regions ◽

Neural Oscillations ◽

Non Invasive ◽

Multiple Electrodes ◽

Transcranial Electric Stimulation ◽

Mechanistic Understanding ◽

Linear Manner ◽

The Brain

ABSTRACTNeural oscillations play a crucial role in communication between remote brain areas. Transcranial electric stimulation with alternating currents (TACS) can manipulate these brain oscillations in a non-invasive manner. Of particular interest, TACS protocols using multiple electrodes with phase shifted stimulation currents were developed to alter the connectivity between two or more brain regions. Typically, an increase in coordination between two sites is assumed when they experience an in-phase stimulation and a disorganization through an anti-phase stimulation. However, the underlying biophysics of multi-electrode TACS has not been studied in detail, thus limiting our ability to develop a mechanistic understanding. Here, we leverage direct invasive recordings from two non-human primates during multi-electrode TACS to show that the electric field magnitude and phase depend on the phase of the stimulation currents in a non-linear manner. Further, we report a novel phenomenon of a “traveling wave” stimulation where the location of the electric field maximum changes over the stimulation cycle. Our results provide a basis for a mechanistic understanding of multi-electrode TACS, necessitating the reevaluation of previously published studies, and enable future developments of novel stimulation protocols.

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Targeting Microglia-Synapse Interactions in Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22052342 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2342

Author(s):

Gaia Piccioni ◽

Dalila Mango ◽

Amira Saidi ◽

Massimo Corbo ◽

Robert Nisticò

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Synaptic Plasticity ◽

Intimate Relationship ◽

Synapse Loss ◽

Disease Modifying Therapy ◽

Inflammatory Signals ◽

Health And Disease ◽

Activity Dependent ◽

The Brain

In this review, we focus on the emerging roles of microglia in the brain, with particular attention to synaptic plasticity in health and disease. We present evidence that ramified microglia, classically believed to be “resting” (i.e., inactive), are instead strongly implicated in dynamic and plastic processes. Indeed, there is an intimate relationship between microglia and neurons at synapses which modulates activity-dependent functional and structural plasticity through the release of cytokines and growth factors. These roles are indispensable to brain development and cognitive function. Therefore, approaches aimed at maintaining the ramified state of microglia might be critical to ensure normal synaptic plasticity and cognition. On the other hand, inflammatory signals associated with Alzheimer’s disease are able to modify the ramified morphology of microglia, thus leading to synapse loss and dysfunction, as well as cognitive impairment. In this context, we highlight microglial TREM2 and CSF1R as emerging targets for disease-modifying therapy in Alzheimer’s disease (AD) and other neurodegenerative disorders.

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Malfunctional Reorganization in the Developing Limbo-Prefrontal System in Animals: Implications for Human Psychoses?

Zeitschrift für Neuropsychologie ◽

10.1024//1016-264x.12.1.8 ◽

2001 ◽

Vol 12 (1) ◽

pp. 8-14

Author(s):

Gertraud Teuchert-Noodt ◽

Ralf R. Dawirs

Keyword(s):

Prefrontal Cortex ◽

Mental Disorders ◽

Dentate Gyrus ◽

Cognitive Functions ◽

Experimental Approach ◽

Regulatory Mechanisms ◽

Hippocampal Dentate Gyrus ◽

Non Invasive ◽

Invasive Method ◽

Activity Dependent

Abstract: Neuroplasticity research in connection with mental disorders has recently bridged the gap between basic neurobiology and applied neuropsychology. A non-invasive method in the gerbil (Meriones unguiculus) - the restricted versus enriched breading and the systemically applied single methamphetamine dose - offers an experimental approach to investigate psychoses. Acts of intervening affirm an activity dependent malfunctional reorganization in the prefrontal cortex and in the hippocampal dentate gyrus and reveal the dopamine position as being critical for the disruption of interactions between the areas concerned. From the extent of plasticity effects the probability and risk of psycho-cognitive development may be derived. Advance may be expected from insights into regulatory mechanisms of neurogenesis in the hippocampal dentate gyrus which is obviously to meet the necessary requirements to promote psycho-cognitive functions/malfunctions via the limbo-prefrontal circuit.

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NON-INVASIVE BCI METHOD: EEG - ELECTROENCEPHALOGRAPHY

International Conference on Technics Technologies and Education ◽

10.15547/ictte.2019.02.095 ◽

2019 ◽

pp. 139-145

Author(s):

Selma Büyükgöze

Keyword(s):

Brain Computer Interface ◽

Computer Interface ◽

Electrode Placement ◽

Eeg Signals ◽

Non Invasive ◽

Brain Signals ◽

Brain States ◽

The Brain

Brain Computer Interface consists of hardware and software that convert brain signals into action. It changes the nerves, muscles, and movements they produce with electro-physiological signs. The BCI cannot read the brain and decipher the thought in general. The BCI can only identify and classify specific patterns of activity in ongoing brain signals associated with specific tasks or events. EEG is the most commonly used non-invasive BCI method as it can be obtained easily compared to other methods. In this study; It will be given how EEG signals are obtained from the scalp, with which waves these frequencies are named and in which brain states these waves occur. 10-20 electrode placement plan for EEG to be placed on the scalp will be shown.

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Drusen in the Peripheral Retina of the Alzheimer’s Eye

Current Alzheimer Research ◽

10.2174/1567205015666180123122637 ◽

2018 ◽

Vol 15 (8) ◽

pp. 743-750 ◽

Cited By ~ 8

Author(s):

Kresimir Ukalovic ◽

Sijia Cao ◽

Sieun Lee ◽

Qiaoyue Tang ◽

Mirza Faisal Beg ◽

...

Keyword(s):

Peripheral Retina ◽

Amyloid Angiopathy ◽

Temporal Region ◽

Future Studies ◽

Eye Tissues ◽

Neuropathological Diagnosis ◽

Ocular Imaging ◽

Cerebral Amyloid ◽

The Brain ◽

Oil Red O

Background: Recent work on Alzheimer's disease (AD) diagnosis focuses on neuroimaging modalities; however, these methods are expensive, invasive, and not available to all patients. Ocular imaging of biomarkers, such as drusen in the peripheral retina, could provide an alternative method to diagnose AD. Objective: This study compares macular and peripheral drusen load in control and AD eyes. Methods: Postmortem eye tissues were obtained from donors with a neuropathological diagnosis of AD. Retina from normal donors were processed and categorized into younger (<55 years) and older (>55 years) groups. After fixation and dissection, 3-6 mm punches of RPE/choroid were taken in macular and peripheral (temporal, superior, and inferior) retinal regions. Oil red O positive drusen were counted and grouped into two size categories: small (<63 μm) and intermediate (63-125 μm). Results: There was a significant increase in the total number of macular and peripheral hard drusen in older, compared to younger, normal eyes (p<0.05). Intermediate hard drusen were more commonly found in the temporal region of AD eyes compared to older normal eyes, even after controlling for age (p<0.05). Among the brain and eye tissues from AD donors, there was a significant relationship between cerebral amyloid angiopathy (CAA) severity and number of temporal intermediate hard drusen (r=0.78, p<0.05). Conclusion: Imaging temporal drusen in the eye may have benefit for diagnosing and monitoring progression of AD. Our results on CAA severity and temporal intermediate drusen in the AD eye are novel. Future studies are needed to further understand the interactions among CAA and drusen formation.

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DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽

10.3390/biom11020142 ◽

2021 ◽

Vol 11 (2) ◽

pp. 142

Author(s):

Mariella Cuomo ◽

Luca Borrelli ◽

Rosa Della Monica ◽

Lorena Coretti ◽

Giulia De Riso ◽

...

Keyword(s):

Dna Methylation ◽

Molecular Mechanisms ◽

The Past ◽

Targeted Analysis ◽

Lack Of Information ◽

High Resolution Power ◽

Resolution Level ◽

Health And Disease ◽

High Doses ◽

The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

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Breeder Diet Strategies for Generating Ttpa-Null and Wild-Type Mice with Low Vitamin E Status to Assess Neurological Outcomes

Current Developments in Nutrition ◽

10.1093/cdn/nzaa155 ◽

2020 ◽

Vol 4 (11) ◽

Author(s):

Katherine M Ranard ◽

Matthew J Kuchan ◽

John W Erdman

Keyword(s):

Animal Model ◽

Vitamin E ◽

Mouse Model ◽

Wild Type ◽

Future Studies ◽

Neurological Outcomes ◽

Transfer Protein ◽

And Function ◽

The Brain ◽

Vitamin E Status

ABSTRACT Studying vitamin E [α-tocopherol (α-T)] metabolism and function in the brain and other tissues requires an animal model with low α-T status, such as the transgenic α-T transfer protein (Ttpa)–null (Ttpa−/−) mouse model. Ttpa+/− dams can be used to produce Ttpa−/− and Ttpa+/+mice for these studies. However, the α-T content in Ttpa+/− dams’ diet requires optimization; diets must provide sufficient α-T for reproduction, while minimizing the transfer of α-T to the offspring destined for future studies that require low baseline α-T status. The goal of this work was to assess the effectiveness and feasibility of 2 breeding diet strategies on reproduction outcomes and offspring brain α-T concentrations. These findings will help standardize the breeding methodology used to generate the Ttpa−/− mice for neurological studies.

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Monitoring New Long-Lasting Intravitreal Formulation for Glaucoma with Vitreous Images Using Optical Coherence Tomography

Pharmaceutics ◽

10.3390/pharmaceutics13020217 ◽

2021 ◽

Vol 13 (2) ◽

pp. 217

Author(s):

Maria Jesus Rodrigo ◽

Amaya Pérez del Palomar ◽

Alberto Montolío ◽

Silvia Mendez-Martinez ◽

Manuel Subias ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Relative Intensity ◽

Therapeutic Option ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Aggregate Size ◽

Daily Practice ◽

Optical Coherence ◽

Non Invasive ◽

Invasive Method

Intravitreal injection is the gold standard therapeutic option for posterior segment pathologies, and long-lasting release is necessary to avoid reinjections. There is no effective intravitreal treatment for glaucoma or other optic neuropathies in daily practice, nor is there a non-invasive method to monitor drug levels in the vitreous. Here we show that a glaucoma treatment combining a hypotensive and neuroprotective intravitreal formulation (IF) of brimonidine–Laponite (BRI/LAP) can be monitored non-invasively using vitreoretinal interface imaging captured with optical coherence tomography (OCT) over 24 weeks of follow-up. Qualitative and quantitative characterisation was achieved by analysing the changes in vitreous (VIT) signal intensity, expressed as a ratio of retinal pigment epithelium (RPE) intensity. Vitreous hyperreflective aggregates mixed in the vitreous and tended to settle on the retinal surface. Relative intensity and aggregate size progressively decreased over 24 weeks in treated rat eyes as the BRI/LAP IF degraded. VIT/RPE relative intensity and total aggregate area correlated with brimonidine levels measured in the eye. The OCT-derived VIT/RPE relative intensity may be a useful and objective marker for non-invasive monitoring of BRI/LAP IF.

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Reactive Oxygen Species: Beyond Their Reactive Behavior

Neurochemical Research ◽

10.1007/s11064-020-03208-7 ◽

2021 ◽

Vol 46 (1) ◽

pp. 77-87

Author(s):

Arnaud Tauffenberger ◽

Pierre J. Magistretti

Keyword(s):

Reactive Oxygen Species ◽

Second Messengers ◽

Critical Role ◽

Complex Function ◽

Reactive Oxygen ◽

High Reactivity ◽

Oxygen Species ◽

Health And Disease ◽

Cellular Dysfunction ◽

The Brain

AbstractCellular homeostasis plays a critical role in how an organism will develop and age. Disruption of this fragile equilibrium is often associated with health degradation and ultimately, death. Reactive oxygen species (ROS) have been closely associated with health decline and neurological disorders, such as Alzheimer’s disease or Parkinson’s disease. ROS were first identified as by-products of the cellular activity, mainly mitochondrial respiration, and their high reactivity is linked to a disruption of macromolecules such as proteins, lipids and DNA. More recent research suggests more complex function of ROS, reaching far beyond the cellular dysfunction. ROS are active actors in most of the signaling cascades involved in cell development, proliferation and survival, constituting important second messengers. In the brain, their impact on neurons and astrocytes has been associated with synaptic plasticity and neuron survival. This review provides an overview of ROS function in cell signaling in the context of aging and degeneration in the brain and guarding the fragile balance between health and disease.

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