Percutaneous Intracerebral Navigation by Duty-Cycled Spinning of Flexible Bevel-Tipped Needles

Neurosurgery ◽  
2010 ◽  
Vol 67 (4) ◽  
pp. 1117-1123 ◽  
Author(s):  
Johnathan A Engh ◽  
Davneet S Minhas ◽  
Douglas Kondziolka ◽  
Cameron N Riviere
Keyword(s):  
Image Guidance ◽  
Neurological Diseases ◽  
Steering System ◽  
Needle Steering ◽  
Future Studies ◽  
Area Of Interest ◽  
Cadaver Testing ◽  
The Brain ◽  
Cadaveric Model

Abstract BACKGROUND: Intracerebral drug delivery using surgically placed microcatheters is a growing area of interest for potential treatment of a wide variety of neurological diseases, including tumors, neurodegenerative disorders, trauma, epilepsy, and stroke. Current catheter placement techniques are limited to straight trajectories. The development of an inexpensive system for flexible percutaneous intracranial navigation may be of significant clinical benefit. OBJECTIVE: Utilizing duty-cycled spinning of a flexible bevel-tipped needle, the authors devised and tested a means of achieving nonlinear trajectories for the navigation of catheters in the brain, which may be applicable to a wide variety of neurological diseases. METHODS: Exploiting the bending tendency of bevel-tipped needles due to their asymmetry, the authors devised and tested a means of generating curvilinear trajectories by spinning a needle with a variable duty cycle (ie, in on-off fashion). The technique can be performed using image guidance, and trajectories can be adjusted intraoperatively via joystick. Fifty-eight navigation trials were performed during cadaver testing to demonstrate the efficacy of the needle-steering system and to test its precision. RESULTS: The needle-steering system achieved a target acquisition error of 2 ± 1 mm, while demonstrating the ability to reach multiple targets from one burr hole using trajectories of varying curvature. CONCLUSION: The accuracy of the needle-steering system was demonstrated in a cadaveric model. Future studies will determine the safety of the device in vivo.

scholarly journals Potential caveats of putative microglia-specific markers for assessment of age-related cerebrovascular neuroinflammation

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Pedram Honarpisheh ◽  
Juneyoung Lee ◽  
Anik Banerjee ◽  
Maria P. Blasco-Conesa ◽  
Parisa Honarpisheh ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Ex Vivo ◽  
Myeloid Cells ◽  
Amyloid Angiopathy ◽  
Future Studies ◽  
Age Related ◽  
In Vivo Animal Models ◽  
Intermediate Expression ◽  
The Brain

Abstract Background The ability to distinguish resident microglia from infiltrating myeloid cells by flow cytometry-based surface phenotyping is an important technique for examining age-related neuroinflammation. The most commonly used surface markers for the identification of microglia include CD45 (low-intermediate expression), CD11b, Tmem119, and P2RY12. Methods In this study, we examined changes in expression levels of these putative microglia markers in in vivo animal models of stroke, cerebral amyloid angiopathy (CAA), and aging as well as in an ex vivo LPS-induced inflammation model. Results We demonstrate that Tmem119 and P2RY12 expression is evident within both CD45int and CD45high myeloid populations in models of stroke, CAA, and aging. Interestingly, LPS stimulation of FACS-sorted adult microglia suggested that these brain-resident myeloid cells can upregulate CD45 and downregulate Tmem119 and P2RY12, making them indistinguishable from peripherally derived myeloid populations. Importantly, our findings show that these changes in the molecular signatures of microglia can occur without a contribution from the other brain-resident or peripherally sourced immune cells. Conclusion We recommend future studies approach microglia identification by flow cytometry with caution, particularly in the absence of the use of a combination of markers validated for the specific neuroinflammation model of interest. The subpopulation of resident microglia residing within the “infiltrating myeloid” population, albeit small, may be functionally important in maintaining immune vigilance in the brain thus should not be overlooked in neuroimmunological studies.

scholarly journals Locus Coeruleus Magnetic Resonance Imaging in Neurological Diseases

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Alessandro Galgani ◽  
Francesco Lombardo ◽  
Daniele Della Latta ◽  
Nicola Martini ◽  
Ubaldo Bonuccelli ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Neurological Disorders ◽  
Potential Role ◽  
Neurological Diseases ◽  
Mri Findings ◽  
Promising Tool ◽  
Experimental Tool ◽  
Early Biomarker ◽  
The Brain

Abstract Purpose of Review Locus coeruleus (LC) is the main noradrenergic nucleus of the brain, and its degeneration is considered to be key in the pathogenesis of neurodegenerative diseases. In the last 15 years,MRI has been used to assess LC in vivo, both in healthy subjects and in patients suffering from neurological disorders. In this review, we summarize the main findings of LC-MRI studies, interpreting them in light of preclinical and histopathological data, and discussing its potential role as diagnostic and experimental tool. Recent findings LC-MRI findings were largely in agreement with neuropathological evidences; LC signal showed to be not significantly affected during normal aging and to correlate with cognitive performances. On the contrary, a marked reduction of LC signal was observed in patients suffering from neurodegenerative disorders, with specific features. Summary LC-MRI is a promising tool, which may be used in the future to explore LC pathophysiology as well as an early biomarker for degenerative diseases.

scholarly journals Magnetic Nanoparticles as In Vivo Tracers for Alzheimer’s Disease

2020 ◽  
Vol 6 (1) ◽  
pp. 13
Author(s):  
Bhargy Sharma ◽  
Konstantin Pervushin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Contrast Agents ◽  
Neurological Diseases ◽  
Pulse Sequences ◽  
Experimental Conditions ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Drug formulations and suitable methods for their detection play a very crucial role in the development of therapeutics towards degenerative neurological diseases. For diseases such as Alzheimer’s disease, magnetic resonance imaging (MRI) is a non-invasive clinical technique suitable for early diagnosis. In this review, we will discuss the different experimental conditions which can push MRI as the technique of choice and the gold standard for early diagnosis of Alzheimer’s disease. Here, we describe and compare various techniques for administration of nanoparticles targeted to the brain and suitable formulations of nanoparticles for use as magnetically active therapeutic probes in drug delivery targeting the brain. We explore different physiological pathways involved in the transport of such nanoparticles for successful entry in the brain. In our lab, we have used different formulations of iron oxide nanoparticles (IONPs) and protein nanocages as contrast agents in anatomical MRI of an Alzheimer’s disease (AD) brain. We compare these coatings and their benefits to provide the best contrast in addition to biocompatibility properties to be used as sustainable drug-release systems. In the later sections, the contrast enhancement techniques in MRI studies are discussed. Examples of contrast-enhanced imaging using advanced pulse sequences are discussed with the main focus on important studies in the field of neurological diseases. In addition, T1 contrast agents such as gadolinium chelates are compared with the T2 contrast agents mainly made of superparamagnetic inorganic metal nanoparticles.

scholarly journals Cell type-specific biotin labeling in vivo resolves regional neuronal proteomic differences in mouse brain

2021 ◽  
Author(s):  
Sruti Rayaprolu ◽  
Sara Bitarafan ◽  
Ranjita Betarbet ◽  
Sydney N Sunna ◽  
Lihong Cheng ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Neurological Diseases ◽  
Neuronal Cell ◽  
Cell Types ◽  
Proteomic Profiling ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific ◽  
The Brain

Isolation and proteomic profiling of brain cell types, particularly neurons, pose several technical challenges which limit our ability to resolve distinct cellular phenotypes in neurological diseases. Therefore, we generated a novel mouse line that enables cell type-specific expression of a biotin ligase, TurboID, via Cre-lox strategy for in vivo proximity-dependent biotinylation of proteins. Using adenoviral-based and transgenic approaches, we show striking protein biotinylation in neuronal cell bodies and axons throughout the mouse brain. We quantified more than 2,000 neuron-derived proteins following enrichment that mapped to numerous subcellular compartments. Synaptic, transmembrane transporters, ion channel subunits, and disease-relevant druggable targets were among the most significantly enriched proteins. Remarkably, we resolved brain region-specific proteomic profiles of Camk2a neurons with distinct functional molecular signatures and disease associations that may underlie regional neuronal vulnerability. Leveraging the neuronal specificity of this in vivo biotinylation strategy, we used an antibody-based approach to uncover regionally unique patterns of neuron-derived signaling phospho-proteins and cytokines, particularly in the cortex and cerebellum. Our work provides a proteomic framework to investigate cell type-specific mechanisms driving physiological and pathological states of the brain as well as complex tissues beyond the brain.

scholarly journals Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury

2016 ◽  
Vol 37 (2) ◽  
pp. 528-540 ◽  
Author(s):  
Nan Jiang ◽  
Junjun Wu ◽  
Tiandong Leng ◽  
Tao Yang ◽  
Yufan Zhou ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Critical Role ◽  
Hippocampal Slices ◽  
Specific Effect ◽  
Neuronal Injury ◽  
Functional Difference ◽  
Striatal Neurons ◽  
The Brain ◽  
Specific Contribution

Acidosis in the brain plays a critical role in neuronal injury in neurological diseases, including brain ischemia. One key mediator of acidosis-induced neuronal injury is the acid-sensing ion channels (ASICs). Current literature has focused on ASIC1a when studying acid signaling. The importance of ASIC2, which is also widely expressed in the brain, has not been appreciated. We found here a region-specific effect of ASIC2 on acid-mediated responses. Deleting ASIC2 reduced acid-activated current in cortical and striatal neurons, but had no significant effect in cerebellar granule neurons. In addition, we demonstrated that ASIC2 was important for ASIC1a expression, and that ASIC2a but not 2b facilitated ASIC1a surface trafficking in the brain. Further, we showed that ASIC2 deletion attenuated acidosis/ischemia-induced neuronal injury in organotypic hippocampal slices but had no effect in organotypic cerebellar slices. Consistent with an injurious role of ASIC2, we showed that ASIC2 deletion significantly protected the mouse brain from ischemic damage in vivo. These data suggest a critical region-specific contribution of ASIC2 to neuronal injury and reveal an important functional difference between ASIC2a and 2b in the brain.

Electrochemical Detection of Neurotransmitters in the Brain and Other Molecules with Biological Activity in the Nervous System: Dopamine Analysis

2020 ◽  
Vol 24 (21) ◽  
pp. 2498-2507
Author(s):  
Erika Bustos ◽  
Juan Manríquez ◽  
Ana Laura Colín-González ◽  
Edgar Rangel-López ◽  
Abel Santamaría
Keyword(s):  
Nervous System ◽  
Biological Activity ◽  
Electrochemical Detection ◽  
Neurological Diseases ◽  
Electrochemical Techniques ◽  
Modified Electrodes ◽  
Analytical Techniques ◽  
The Brain

Monitoring the appropriate functions of the brain is a priority when the diagnosis of neurological diseases is carried out. In this regard, there are different analytical techniques to detect neurotransmitters and other molecules with biological activity in the nervous system. Among several analytical procedures, electrochemical techniques are very important since they can be applied in situ, without loss of sensibility and/or minimal handling of samples. In addition, it is also possible to combine them with specific detectors designed on the basis of chemically-modified electrodes in order to improve detection limits by promoting molecular recognition capabilities at their surfaces, thus favoring the development of electrochemical detection in vivo by microelectrodes. In this mini-review, we will describe the major characteristics of this analytical method and its advantages for the detection of neurotransmitters (mostly dopamine) in vivo.

Recent Advances in Nanotechnology-Based Drug Delivery Approaches for Alzheimer disease

2021 ◽  
Vol 22 ◽  
Author(s):  
Ishnoor Kaur ◽  
Arun Kumar ◽  
Tapan Behl ◽  
Dhruv Setia
Keyword(s):  
Drug Delivery ◽  
Biomedical Applications ◽  
Drug Loading ◽  
Transport Mechanisms ◽  
Long Term Effects ◽  
Future Studies ◽  
Β Amyloid ◽  
The Brain

Abstract: One of the most common form of neurodegenerative disorders, Alzheimer’s disease poses a great threat to the patients all over the globe with about 5.7 million cases estimated by the Alzheimer’s Association Report of 2018. The disorder is a result of β-amyloid deposition in the brain, deteriorating the cognitive ability and learning processes, commonly in geriatric patients. The review significantly elaborates the superiority of nanotechnological formulations over conventional therapeutic strategies which exhibit numerous side effects, poor pharmacokinetic profiles and limited efficacy, as compared to the nano-medicinal approach. The review recognizes the need to establish an understanding of the transport mechanisms across the blood brain barrier, prior to the nanoparticle studies, followed by discussion on various nano-formulations, evi-dently supported by the outcome of various studies conducted to investigate the drug delivery portfolio of nanomedicines. Furthermore, the review portrays the challenges to overcome in future studies, like nanoparticle fabrication, drug loading capacity, blood residency time, toxicity regime, monitoring long term effects, in-vivo compatibility and production tech-niques, in order to enable the development of an optimized form of drug delivery process, which would achieve significant heights in the biomedical applications and bring about a revolution in the field of medicine and science.

scholarly journals In Vivo Imaging with Bioluminescent Enterovirus 71 Allows for Real-Time Visualization of Tissue Tropism and Viral Spread

2016 ◽  
Vol 91 (5) ◽  
Author(s):  
Elizabeth A. Caine ◽  
Jorge E. Osorio
Keyword(s):  
Real Time ◽  
Enterovirus 71 ◽  
Neurological Complications ◽  
Ev71 Infection ◽  
Tissue Tropism ◽  
Future Studies ◽  
Viral Spread ◽  
Real Time Visualization ◽  
The Brain

ABSTRACT Hand, foot, and mouth disease (HFMD) is a reemerging illness caused by a variety of enteroviruses. The main causative agents are enterovirus 71 (EV71), coxsackievirus A16 (CVA16), and, most recently, coxsackievirus A6 (CVA6). Enterovirus infections can vary from asymptomatic infections to those with a mild fever and blisters on infected individuals' hands, feet, and throats to infections with severe neurological complications. Viral persistence for weeks postinfection (wpi) has also been documented by the demonstration of virus in children's stools. However, little is known about disease progression, viral spread, and tissue tropism of these viruses. These types of studies are limited because many recently developed mouse models mimic the severe neurological complications that occur in a small percentage of enterovirus infections. In the present study, we documented real-time EV71 infection in two different mouse strains by the use of in vivo imaging. Infection of BALB/c mice with a bioluminescent mouse-adapted EV71 construct (mEV71-NLuc) resulted in a lack of clinical signs of disease but in relatively high viral replication, as visualized by luminescence, for 2 wpi. In contrast, mEV71-NLuc infection of AG129 mice (alpha/beta and gamma interferon receptor deficient) showed rapid spread and long-term persistence of the virus in the brain. Interestingly, AG129 mice that survived infection maintained luminescence in the brain for up to 8 wpi. The results we present here will allow future studies on EV71 antiviral drug susceptibility, vaccine efficacy, transmissibility, and pathogenesis. IMPORTANCE We report here that a stable full-length enterovirus 71 (EV71) reporter construct was used to visualize real-time viral spread in AG129 and BALB/c mice. To our knowledge, this is the first report of in vivo imaging of infection with any member of the Picornaviridae family. The nanoluciferase (NLuc) gene, one of the smallest luciferase genes currently available, was shown to be stable in the EV71 genome for eight passages on rhabdomyosarcoma cells. Real-time visualization of EV71 infection in mice identified areas of tropism that would have been missed by traditional methods, including full characterization of EV71 replication in BALB/c mice. Additionally, the bioluminescent construct allowed for increased speed and sensitivity of cell culture assays and will allow future studies involving various degrees of enterovirus infection in mice, not just severe infections. Our data suggest that interferon plays an important role in controlling EV71 infection in the central nervous system of mice.

scholarly journals Multifunctional Superparamagnetic Stiff Nanoreservoirs for Blood Brain Barrier Applications

Nanomaterials ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 449 ◽  
Author(s):  
Zulema Vargas-Osorio ◽  
Andrés Da Silva-Candal ◽  
Yolanda Piñeiro ◽  
Ramón Iglesias-Rey ◽  
Tomas Sobrino ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Neurological Diseases ◽  
Developed Countries ◽  
Large Set ◽  
In Vivo Experiments ◽  
Liver And Kidney ◽  
The Brain

Neurological diseases (Alzheimer’s disease, Parkinson’s disease, and stroke) are becoming a major concern for health systems in developed countries due to the increment of ageing in the population, and many resources are devoted to the development of new therapies and contrast agents for selective imaging. However, the strong isolation of the brain by the brain blood barrier (BBB) prevents not only the crossing of pathogens, but also a large set of beneficial drugs. Therefore, an alternative strategy is arising based on the anchoring to vascular endothelial cells of nanoplatforms working as delivery reservoirs. In this work, novel injectable mesoporous nanorods, wrapped by a fluorescent magnetic nanoparticles envelope, are proposed as biocompatible reservoirs with an extremely high loading capacity, surface versatility, and optimal morphology for enhanced grafting to vessels during their diffusive flow. Wet chemistry techniques allow for the development of mesoporous silica nanostructures with tailored properties, such as a fluorescent response suitable for optical studies, superparamagnetic behavior for magnetic resonance imaging MRI contrast, and large range ordered porosity for controlled delivery. In this work, fluorescent magnetic mesoporous nanorods were physicochemical characterized and tested in preliminary biological in vitro and in vivo experiments, showing a transversal relaxivitiy of 324.68 mM−1 s−1, intense fluorescence, large specific surface area (300 m2 g−1), and biocompatibility for endothelial cells’ uptake up to 100 µg (in a 80% confluent 1.9 cm2 culture well), with no liver and kidney disability. These magnetic fluorescent nanostructures allow for multimodal MRI/optical imaging, the allocation of therapeutic moieties, and targeting of tissues with specific damage.

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