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(SD2021-057) Electro-optical mechanically flexible neural probes

Microelectrodes are the gold standard for measuring the activity of individual neurons at high temporal resolution in any nervous system region and central to defining the role of neural circuits in controlling behavior. Microelectrode technologies such as the Utah or Michigan arrays, have allowed tracking of distributed neural activity with millisecond precision. However, their large footprint and rigidity lead to tissue damage and inflammation that hamper long-term recordings. State of the art Neuropixel and carbon fiber probes have improved on these previous devices by increasing electrode density and reducing probe dimensions and rigidity. Although these probes have advanced the field of recordings, next-generation devices should enable targeted stimulation in addition to colocalized electrical recordings. Optogenetic techniques enable high-speed modulation of cellular activity through targeted expression and activation of light-sensitive opsins. However, given the strong light scattering and high absorption properties of neural tissue optogenetic interfacing with deep neural circuits typically requires the implantation of large-diameter rigid fibers, which can make this approach more invasive than its electrical counterpart.Approaches to integrating optical and electrical modalities have ranged from adding fiber optics to existing Utah arrays to the Optetrode or other integrated electro-optical coaxial structures. These technologies have shown great promise for simultaneous electrical recordings and optical stimulation in vivo. However, the need to reduce the device footprint to minimize immune responses for long-term recordings is still present.

Sequential Targeting and Crosslinking Nanoparticles for Tackling the Multiple Barriers to Treat Brain Tumors

Researchers at the University of California, Davis have developed an approach to improve drug delivery to tumors and metastases in the brain. Their multi-barrier tackling delivery strategy has worked to efficiently impact brain tumor management while also achieving increased survival times in anti-cancer efficacy.

(SD2021-314) MULTI-THOUSAND CHANNEL ELECTROPHYSIOLOGY ARRAYS

Electrophysiological devices are critical for mapping eloquent and diseased brain regions and for therapeutic neuromodulation in clinical settings and are extensively utilized for research in brain-machine interfaces. However, the existing devices are often limited in either spatial resolution or cortical coverage, even including those with thousands of channels used in animal experiments.

(SD2020-421) Virtual Electrodes for Imaging of Cortex-Wide Brain Activity: Decoding of cortex-wide brain activity from local recordings of neural potentials

As an important tool for electrophysiological recordings, neural electrodes implanted on the brain surface have been instrumental in basic neuroscience research to study large-scale neural dynamics in various cognitive processes, such as sensorimotor processing as well as learning and memory. In clinical settings, neural recordings have been adopted as a standard tool to monitor the brain activity in epilepsy patients before surgery for detection and localization of epileptogenic zones initiating seizures and functional cortical mapping. Neural activity recorded from the brain surface exhibits rich information content about the collective neural activities reflecting the cognitive states and brain functions. For the interpretation of surface potentials in terms of their neural correlates, most research has focused on local neural activities.   From basic neuroscience research to clinical treatments and neural engineering, electrocorticography (ECoG) has been widely used to record surface potentials to evaluate brain function and develop neuroprosthetic devices. However, the requirement of invasive surgeries for implanting ECoG arrays significantly limits the coverage of different cortical regions, preventing simultaneous recordings from spatially distributed cortical networks. However, this rich information content of surface potentials encoded for the large-scale cortical activity remains unexploited and little is known on how local surface potentials are correlated with the spontaneous neural activities of distributed large-scale cortical networks. Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0in; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

Novel Agonist alpha2aAR Analgesics

Brief description not available

(SD2021-057) Electro-optical mechanically flexible microprobes for minimally invasive interfacing with intrinsic neural circuits

Microelectrodes are the gold standard for measuring the activity of individual neurons at high temporal resolution in any nervous system region and central to defining the role of neural circuits in controlling behavior.Microelectrode technologies such as the Utah or Michigan arrays, have allowed tracking of distributed neural activity with millisecond precision. However, their large footprint and rigidity lead to tissue damage and inflammation that hamper long-term recordings. State of the art Neuropixel and carbon fiber probes have improved on these previous devices by increasing electrode density and reducing probe dimensions and rigidity.Although these probes have advanced the field of recordings, next-generation devices should enable targeted stimulation in addition to colocalized electrical recordings. Optogenetic techniques enable high-speed modulation of cellular activity through targeted expression and activation of light-sensitive opsins. However, given the strong light scattering and high absorption properties of neural tissue optogenetic interfacing with deep neural circuits typically requires the implantation of large-diameter rigid fibers, which can make this approach more invasive than its electrical counterpart.Approaches to integrating optical and electrical modalities have ranged from adding fiber optics to existing Utah arrays to the Optetrode or other integrated electro-optical coaxial structures. These technologies have shown great promise for simultaneous electrical recordings and optical stimulation in vivo. However, the need to reduce the device footprint to minimize immune responses for long-term recordings is still present.

Novel Estrogen Receptor ß (ERß) Drugs for the Treatment of Multiple Sclerosis (MS)

Prof. Seema K. Tiwari-Woodruff from the University of California, Riverside, Prof. John Katzellenbogen and colleagues from the University of Illinois have developed novel estrogen receptor β (ERβ) drugs for the treatment of MS. These novel MS drugs are specific for ERβ and have tremendous potential for the treatment of MS as well as other neurodegenerative diseases. In general, estrogens have anti-inflammatory and neuroprotective activities and clinically reduce the severity of MS and other neurodegenerative diseases. The compounds are more superior to other estrogenic drugs due to their specificity for ERβ and lack of undesirable effects such as feminization and increased risk of cancer. Fig 1: Therapeutic treatment with the UCR ERβ ligands began at peak disease (day 17) and was continued daily till day 36. ERβ ligands (blue, and orange) significantly attenuated clinical disease severity compared to vehicle treatment (red).  

Device for Spinal Dural Repair

Dural tear is a frequent and costly complication of spinal surgery, which can cause cerebrospinal fluid (CSF) leakage, triggering additional, serious post-operative difficulties. Researchers at UC Irvine have developed a new method and device to mitigate dural tears in a rapid, safe, and water-tight manner

(SD2018-098) Platinum Nanorod Electrode Arrays For Highly Sensitive And Initiative Brain-Machine Interfaces

The enhanced electrochemical activity of nanostructured materials is readily exploited in energy devices, but their utility in scalable and human-compatible implantable neural interfaces can significantly advance the performance of clinical and research electrodes. Traditional biologically inert noble metals such as Pt, Ir or IrPt – are preferential material choices for manufacturing nerve electrodes/ biomedical devices in clinical-relevant applications because of their biocompatibility and stability against corrosion, and because of their superior electrochemical properties compared to other material combinations. But despite these superior properties, the electrochemical interface impedance is not sufficiently low to enable recording minute potential fluctuations with low noise baseline or to efficiently inject charges across the interface without building large voltages across the interface and therefore consuming larger powers per pulse.  As a result, large electrodes are needed to compensate for this large impedance, but large electrodes compromise spatial resolution and specificity for recording and/or stimulation and limit the density and overall number of contacts. To increase the surface area and decrease the electrochemical impedance, nano-structures are often incorporated onto electrode surfaces to enhance their electrochemical properties. Prior work has successfully incorporated nano-structured Pt into electrodes, using electrochemical methods (electro-plating) , but these electrodes suffered from poor structural integrity and physical strength due to incorporation of electrochemical surfactants at the interface between nano-structured Pt and the underlying electrode. Furthermore, common approaches for the fabrication of nano-structured Pt are generally not monolithic and face additional challenges for translation to clinical practice whereas some are also problematic due to the residual of toxic ligand additives remaining after Pt alloy electro-deposition.  

Inhibitors of Bromodomain and Extra-Terminal (BET) Family Proteins as Potential Treatments for Drug-Resistant Tumors

Researchers at the University of California, Davis have developed small molecule inhibitors for use in treating drug-resistant tumors – including cancerous tumors.

Intranasal Delivery of Oligonucleotides for Neurodegenerative Diseases

Delivery of oligonucleotide therapy to the central nervous system remains challenging. Neurodegenerative diseases, such as Huntington’s disease and Spinal Muscular Atrophy, can require intrusive and regular treatments, therefore a non-invasive delivery system would be very beneficial to patients. UC Irvine researchers have proposed a new method of therapeutic delivery utilizing a SARS-CoV-2 pseudovirus. Delivered intranasally, this system has the ability to bypass the blood brain barrier, making it an exciting approach to decrease risk for patients and ease the treatment process.

Novel Positron Emission Tomography Agents for Imaging Neurodegeneration

New positron emission tomography (PET) imaging agent developed that uniquely binds to synucleinopathies and tauopathies in the Parkinson’s brain and may therefore serve as an early diagnostic marker.

Virtual Reality For Anhedonia Program

UCLA researchers in the Department of Psychology have developed a behavioral training program for the improvement of anhedonia.

Exosome-Mimicking Nanovesicles

Researchers at the University of California, Davis have developed a method of synthesizing stem cell-derived, exosome-mimicking, nanovesicles that have the therapeutic potential to rescue apoptotic neurons in culture.

Steroid Regulation Of Inwardly Rectifying K+ Channel As Therapeutics Tool

UC Berkeley researches have discovered a new physiological modality of a potassium channel that is linked to the process of fluid regulation in the brain and is expressed in the choroid plexus (CP) and retinal pigment epithelia. CP is the main producer of cerebrospinal fluid that serves as a buffer to protect the brain, provides it with nutrients and removes waste products. The researchers have shown that application of progesterone resulted in strong potentiation of the inwardly rectifying potassium channel. The potentiation was progesterone-specific and independent of other known membrane progesterone receptors expressed in CP. 

Novel Treatment For Alzheimer’s Disease and Dementia

Pathological accumulation of phosphorylated Tau (pTau) and accumulation of amyloid-beta (Ab) fragments are the two major biochemical hallmarks of Alzheimer’s disease (AD). Effective strategies to remove Ab in AD-patient brains have been developed, but have not yet shown efficacy to slow cognitive decline in clinical trials. This finding has led to the idea that targeting Tau or combinatorial strategies that target both Tau and Ab are required to treat AD. Genetic, epidemiologic, and biochemical evidence suggests that predisposition to AD may arise from altered cholesterol metabolism, although the molecular pathways that may link cholesterol to AD phenotypes are only partially understood. Stimulation of a brain specific cytochrome that converts cholesterol to 24-hydroxycholesterol, which in turn reduces cholesteryl ester. Reduction of cholesteryl ester has been demonstrated to reduce pathological Tau phosphorylation in human neurons made from induced pluripotent stem cells. Also, low dose Efavirenz/Sustiva reduces neurofibrillary tangles in a mouse model. The pathway may run from cholesteryl ester to Tau via the proteasome.

Metal‐Binding Pharmacophore Library Yields the Discovery of a Glyoxalase 1 Inhibitor for Potential Treatment of Depression and Related Psychiatric Illnesses.

Anxiety and depression are the two most common psychiatric disorders in the U.S. and affect approximately one-in-five adults at some point in their lifetime. Depression is the leading cause of worldwide disability; anxiety disorders are highly comorbid with depression. Presently, there are several drugs approved by the U.S. Food and Drug Administration for the treatment of both anxiety and depression; however, these drugs have several important limitations. Antidepressant drugs are not effective in all patients, take weeks to produce therapeutic effects, and produce side effects that limit their use. Anxiolytic drugs produce sedating side effects and have significant abuse liability. Therefore, there is an urgent need for better therapeutic agents. Recent studies using both genetic and pharmacological techniques have implicated GLO1 in numerous behaviors, including several that are relevant to depression and anxiety.

Oldest-Old Mri Registration Template

MRI scans of patients/participants can be compared to template scans in order to identify differences or changes in brain anatomy. However, the templates that are used are typically of young brains, which lack the atrophy that naturally occurs in the aged brain. UCI researchers have developed a template for oldest old images (90+ age group) that takes into consideration the natural anatomical changes that can occur with aging.

Effective Repetitive Transcranial Magnetic Stimulation (rTMS) Taking in Account Real-Time Frequency and Phase Of Intrinsic Brain Activity

Current research and practice in the field of therapeutic rTMS is not taking into account 1) inter-individual variability 2) variability between brain areas 3) variability or differences between oscillations in distinct and overlapping frequency bands, 4) existence of high- and low-excitability phase periods in each oscillatory cycle. Clinical treatments with rTMS and experimental research findings show mixed effects, with rTMS protocols inducing variable degrees of brain plasticity over subjects and sessions.

Peptide Mediated Oligonucleotide Delivery to the CNS

Many diseases of the central nervous system (CNS) arise from the accumulation of proteins such as α-synuclein (aSyn) in Parkinson’s Disease (PD) or Aß in Alzheimer’s disease (AD). The ability to regulate the expression at the gene transcription level would be beneficial for reducing the accumulation of these proteins or regulating expression levels of other genes in the CNS. aSyn also accumulates in other neurodegenerative diseases including dementia with Lewy Body (DLB), multiple system atrophy (MSA) and Gaucher’s disease. This means that regulation of aSyn expression may be crucial to the therapeutic control of numerous neurodegenerative diseases.

Biomimetic Conductive Hydrogels

UCLA researchers in the Department of Bioengineering have developed a novel electrically conductive scaffold system with a hyaluronic acid (HA)-based hydrogel for biomimetic research to treat spinal cord and other central nervous system (CNS) injuries.

Blocking Synaptogenesis For Chronic Pain Management

Gabapentin is used for treatment of seizures and hypersensitivity to pain. Researchers at UCI have employed low-dosage gabapentin immediately after injury to block the development of chronic pain.

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