A microfabricated, 3D-sharpened silicon shuttle for insertion of flexible electrode arrays through dura mater into brain

AbstractElectrode arrays for chronic implantation in the brain are a critical technology in both neuroscience and medicine. Recently, flexible, thin-film polymer electrode arrays have shown promise in facilitating stable, single-unit recordings spanning months in rats. While array flexibility enhances integration with neural tissue, it also requires removal of the dura mater, the tough membrane surrounding the brain, and temporary bracing to penetrate the brain parenchyma. Durotomy increases brain swelling, vascular damage, and surgical time. Insertion using a bracing shuttle results in additional vascular damage and brain compression, which increase with device diameter; while a higher-diameter shuttle will have a higher critical load and more likely penetrate dura, it will damage more brain parenchyma and vasculature. One way to penetrate the intact dura and limit tissue compression without increasing shuttle diameter is to reduce the force required for insertion by sharpening the shuttle tip. We describe a novel design and fabrication process to create silicon insertion shuttles that are sharp in three dimensions and can penetrate rat dura, for faster, easier, and less damaging implantation of polymer arrays. Sharpened profiles are obtained by reflowing patterned photoresist, then transferring its sloped profile to silicon with dry etches. We demonstrate that sharpened shuttles can reliably implant polymer probes through dura to yield high quality single unit and local field potential recordings for at least 95 days. On insertion directly through dura, tissue compression is minimal. This is the first demonstration of a rat dural-penetrating array for chronic recording. This device obviates the need for a durotomy, reducing surgical time and risk of damage to the blood-brain barrier. This is an improvement to state-of-the-art flexible polymer electrode arrays that facilitates their implantation, particularly in multi-site recording experiments. This sharpening process can also be integrated into silicon electrode array fabrication.

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Primary Cranial Vault Lymphoma Extending between Subcutaneous Tissue and Brain Parenchyma without Skull Destruction after Mild Head Trauma: A Case Report and Literature Review

Case Reports in Oncology ◽

10.1159/000516272 ◽

2021 ◽

pp. 1118-1123

Author(s):

Kengo Setta ◽

Takaaki Beppu ◽

Yuichi Sato ◽

Hiroaki Saura ◽

Junichi Nomura ◽

...

Keyword(s):

Tumor Cells ◽

Head Trauma ◽

Dura Mater ◽

Subcutaneous Tissue ◽

Bone Destruction ◽

B Cell Lymphoma ◽

Brain Parenchyma ◽

Skin Tumor ◽

Cranial Vault ◽

The Brain

Malignant lymphoma of the head rarely arises outside of the brain parenchyma as primary cranial vault lymphoma (PCVL). A case of PCVL that invaded from subcutaneous tissue into the brain, passing through the skull, and occurred after mild head trauma is reported along with a review of the literature. The patient was a 75-year-old man with decreased activity. One month before his visit to our hospital, he bruised the left frontal area of his head. Magnetic resonance imaging showed homogeneously enhanced tumors with contrast media in the subcutaneous tissue corresponding to the head impact area and the cerebral parenchyma, but no obvious abnormal findings in the skull. A biopsy with craniotomy was performed under general anesthesia. The pathological diagnosis was diffuse large B-cell lymphoma. On histological examination, tumor cells grew aggressively under the skin. Tumor cells invaded along the emissary vein into the external table without remarkable bone destruction and extended across the skull through the Haversian canals in the diploe. Tumor cells were found only at the perivascular areas in the dura mater and extended into the brain parenchyma. Considering the history of head trauma and the neuroimaging and histological findings, the PCVL in the present case arose primarily under the skin, passed though the skull and dura mater, and invaded along vessels and reached the brain.

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An immunohistochemical study of lymphatic elements in the human brain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2002574118 ◽

2021 ◽

Vol 118 (3) ◽

pp. e2002574118

Author(s):

Éva Mezey ◽

Ildikó Szalayova ◽

Christopher T. Hogden ◽

Alexandra Brady ◽

Ágnes Dósa ◽

...

Keyword(s):

Human Brain ◽

Dura Mater ◽

Cranial Nerves ◽

Lamina Cribrosa ◽

Brain Parenchyma ◽

Pia Mater ◽

Postmortem Human Brain ◽

Waste Products ◽

T Cell Migration ◽

The Brain

Almost 150 papers about brain lymphatics have been published in the last 150 years. Recently, the information in these papers has been synthesized into a picture of central nervous system (CNS) “glymphatics,” but the fine structure of lymphatic elements in the human brain based on imaging specific markers of lymphatic endothelium has not been described. We used LYVE1 and PDPN antibodies to visualize lymphatic marker-positive cells (LMPCs) in postmortem human brain samples, meninges, cavernous sinus (cavum trigeminale), and cranial nerves and bolstered our findings with a VEGFR3 antibody. LMPCs were present in the perivascular space, the walls of small and large arteries and veins, the media of large vessels along smooth muscle cell membranes, and the vascular adventitia. Lymphatic marker staining was detected in the pia mater, in the arachnoid, in venous sinuses, and among the layers of the dura mater. There were many LMPCs in the perineurium and endoneurium of cranial nerves. Soluble waste may move from the brain parenchyma via perivascular and paravascular routes to the closest subarachnoid space and then travel along the dura mater and/or cranial nerves. Particulate waste products travel along the laminae of the dura mater toward the jugular fossa, lamina cribrosa, and perineurium of the cranial nerves to enter the cervical lymphatics. CD3-positive T cells appear to be in close proximity to LMPCs in perivascular/perineural spaces throughout the brain. Both immunostaining and qPCR confirmed the presence of adhesion molecules in the CNS known to be involved in T cell migration.

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Comprehensive chronic laminar single-unit, multi-unit, and local field potential recording performance with planar single shank electrode arrays

Journal of Neuroscience Methods ◽

10.1016/j.jneumeth.2014.12.010 ◽

2015 ◽

Vol 242 ◽

pp. 15-40 ◽

Cited By ~ 64

Author(s):

Takashi D.Y. Kozai ◽

Zhanhong Du ◽

Zhannetta V. Gugel ◽

Matthew A. Smith ◽

Steven M. Chase ◽

...

Keyword(s):

Local Field ◽

Local Field Potential ◽

Single Unit ◽

Field Potential ◽

Electrode Arrays ◽

Potential Recording ◽

Field Potential Recording

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A Simple Method to Avoid Brain Shift during Neuronavigation: Technical Note

Arquivos Brasileiros de Neurocirurgia Brazilian Neurosurgery ◽

10.1055/s-0040-1716560 ◽

2020 ◽

Author(s):

Jair Leopoldo Raso

Keyword(s):

Dura Mater ◽

Brain Area ◽

Conventional Technique ◽

Technical Note ◽

Cortical Surface ◽

Brain Shift ◽

Simple Method ◽

Cortex Area ◽

Neuronavigation System ◽

The Brain

Abstract Introduction The precise identification of anatomical structures and lesions in the brain is the main objective of neuronavigation systems. Brain shift, displacement of the brain after opening the cisterns and draining cerebrospinal fluid, is one of the limitations of such systems. Objective To describe a simple method to avoid brain shift in craniotomies for subcortical lesions. Method We used the surgical technique hereby described in five patients with subcortical neoplasms. We performed the neuronavigation-guided craniotomies with the conventional technique. After opening the dura and exposing the cortical surface, we placed two or three arachnoid anchoring sutures to the dura mater, close to the edges of the exposed cortical surface. We placed these anchoring sutures under microscopy, using a 6–0 mononylon wire. With this technique, the cortex surface was kept close to the dura mater, minimizing its displacement during the approach to the subcortical lesion. In these five cases we operated, the cortical surface remained close to the dura, anchored by the arachnoid sutures. All the lesions were located with a good correlation between the handpiece tip inserted in the desired brain area and the display on the navigation system. Conclusion Arachnoid anchoring sutures to the dura mater on the edges of the cortex area exposed by craniotomy constitute a simple method to minimize brain displacement (brain-shift) in craniotomies for subcortical injuries, optimizing the use of the neuronavigation system.

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Sources of the Scalp-Recorded Amplitude-Modulation Following Response

Journal of the American Academy of Audiology ◽

10.1055/s-0040-1715963 ◽

2002 ◽

Vol 13 (04) ◽

pp. 188-204 ◽

Cited By ~ 53

Author(s):

Shigeyuki Kuwada ◽

Julia S. Anderson ◽

Ranjan Batra ◽

Douglas C. Fitzpatrick ◽

Natacha Teissier ◽

...

Keyword(s):

Animal Model ◽

Amplitude Modulation ◽

Single Unit ◽

Modulation Frequency ◽

Multiple Sources ◽

High Modulation ◽

Before And After ◽

Single Unit Recordings ◽

Composite Response ◽

The Brain

The scalp-recorded amplitude-modulation following response (AMFR)” is gaining recognition as an objective audiometric tool, but little is known about the neural sources that underlie this potential. We hypothesized, based on our human studies and single-unit recordings in animals, that the scalp-recorded AMFR reflects the interaction of multiple sources. We tested this hypothesis using an animal model, the unanesthetized rabbit. We compared AMFRs recorded from the surface of the brain at different locations and before and after the administration of agents likely to enhance or suppress neural generators. We also recorded AMFRs locally at several stations along the auditory neuraxis. We conclude that the surface-recorded AMFR is indeed a composite response from multiple brain generators. Although the response at any modulation frequency can reflect the activity of more than one generator, the AMFRs to low and high modulation frequencies appear to reflect a strong contribution from cortical and subcortical sources, respectively.

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Macrophages and microglia: the cerberus of glioblastoma

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01156-z ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Alice Buonfiglioli ◽

Dolores Hambardzumyan

Keyword(s):

Tumor Cells ◽

Innate Immune System ◽

Tumor Heterogeneity ◽

Expression Profiles ◽

Brain Parenchyma ◽

Innate Immune ◽

Malignant Growth ◽

Neoplastic Cells ◽

Functional Roles ◽

The Brain

AbstractGlioblastoma (GBM) is the most aggressive and deadliest of the primary brain tumors, characterized by malignant growth, invasion into the brain parenchyma, and resistance to therapy. GBM is a heterogeneous disease characterized by high degrees of both inter- and intra-tumor heterogeneity. Another layer of complexity arises from the unique brain microenvironment in which GBM develops and grows. The GBM microenvironment consists of neoplastic and non-neoplastic cells. The most abundant non-neoplastic cells are those of the innate immune system, called tumor-associated macrophages (TAMs). TAMs constitute up to 40% of the tumor mass and consist of both brain-resident microglia and bone marrow-derived myeloid cells from the periphery. Although genetically stable, TAMs can change their expression profiles based upon the signals that they receive from tumor cells; therefore, heterogeneity in GBM creates heterogeneity in TAMs. By interacting with tumor cells and with the other non-neoplastic cells in the tumor microenvironment, TAMs promote tumor progression. Here, we review the origin, heterogeneity, and functional roles of TAMs. In addition, we discuss the prospects of therapeutically targeting TAMs alone or in combination with standard or newly-emerging GBM targeting therapies.

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Practical application of synthetic head models in real ballistic cases

International Journal of Legal Medicine ◽

10.1007/s00414-021-02671-3 ◽

2021 ◽

Author(s):

F. Riva ◽

T. Fracasso ◽

A. Guerra ◽

P. Genet

Keyword(s):

Soft Tissues ◽

Spherical Model ◽

Brain Parenchyma ◽

Human Bone ◽

Shape Model ◽

The Difference ◽

Open Shape ◽

The Brain ◽

Synthetic Models ◽

Representative Material

AbstractIn shooting crimes, ballistics tests are often recommended in order to reproduce the wound characteristics of the involved persons. For this purpose, several “simulants” can be used. However, despite the efforts in the research of “surrogates” in the field of forensic ballistic, the development of synthetic models needs still to be improved through a validation process based on specific real caseworks. This study has been triggered by the findings observed during the autopsy performed on two victims killed in the same shooting incident, with similar wounding characteristics; namely two retained head shots with ricochet against the interior wall of the skull; both projectiles have been recovered during the autopsies after migration in the brain parenchyma. The thickness of the different tissues and structures along the bullets trajectories as well as the incident angles between the bullets paths and the skull walls have been measured and reproduced during the assemblage of the synthetic head models. Two different types of models (“open shape” and “spherical”) have been assembled using leather, polyurethane and gelatine to simulate respectively skin, bone and soft tissues. Six shots have been performed in total. The results of the models have been compared to the findings of post-mortem computed tomography (PMCT) and the autopsy findings.Out of the six shots, two perforated the models and four were retained. When the projectile was retained, the use of both models allowed reproducing the wounds characteristics observed on both victims in terms of penetration and ricochet behaviour. However, the projectiles recovered from the models showed less deformation than the bullets collected during the autopsies. The “open shape” model allowed a better controlling on the shooting parameters than the “spherical” model. Finally, the difference in bullet deformation could be caused by the choice of the bone simulant, which might under-represent either the strength or the density of the human bone. In our opinion, it would be worth to develop a new, more representative material for ballistic which simulates the human bone.

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Microglial Function and Regulation during Development, Homeostasis and Alzheimer’s Disease

Cells ◽

10.3390/cells10040957 ◽

2021 ◽

Vol 10 (4) ◽

pp. 957

Author(s):

Brad T. Casali ◽

Erin G. Reed-Geaghan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immune Cells ◽

Expression Patterns ◽

Brain Parenchyma ◽

Primary Role ◽

And Function ◽

Inflammatory Milieu ◽

The Brain ◽

Homeostatic State

Microglia are the resident immune cells of the brain, deriving from yolk sac progenitors that populate the brain parenchyma during development. During development and homeostasis, microglia play critical roles in synaptogenesis and synaptic plasticity, in addition to their primary role as immune sentinels. In aging and neurodegenerative diseases generally, and Alzheimer’s disease (AD) specifically, microglial function is altered in ways that significantly diverge from their homeostatic state, inducing a more detrimental inflammatory environment. In this review, we discuss the receptors, signaling, regulation and gene expression patterns of microglia that mediate their phenotype and function contributing to the inflammatory milieu of the AD brain, as well as strategies that target microglia to ameliorate the onset, progression and symptoms of AD.

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CTNI-03. IMAGING FEATURES OF LEPTOMENINGEAL METASTASES OF NON-SMALL CELL LUNG CANCER: A SINGLE-CENTER REAL-WORLD STUDY

Neuro-Oncology ◽

10.1093/neuonc/noaa215.170 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii41-ii41

Author(s):

Junjie Zhen ◽

Lei Wen ◽

Shaoqun Li ◽

Mingyao Lai ◽

Changguo Shan ◽

...

Keyword(s):

Spinal Cord ◽

Type A ◽

Brain Parenchyma ◽

Imaging Features ◽

Type B ◽

Type D ◽

Mri Examination ◽

Mri Features ◽

Brain And Spinal Cord ◽

The Brain

Abstract BACKGROUND According to EANO-ESMO clinical practice guidelines, the MRI findings of LM are divided into 4 types, namely linear enhancement (type A), nodular enhancement (type B), linear combined with nodular enhancement (type C), and sign of hydrocephalus (type D). METHODS The MRI features of brain and spinal cord in patients diagnosed with NSCLC-LM in Guangdong Sanjiu Brain Hospital from 2010 until 2019 were investigated, and then were classified into 4 types. The imaging features were analyzed. RESULTS A total of 80 patients were enrolled in the study. The median age of the patients was 53.5 years old, and the median time from the initial diagnosis to the confirmed diagnosis of LM was 11.6 months. The results of enhanced MRI examination of the brain in 79 cases showed that the number of cases with enhancements of type A, B, C and D were 50 (63.3%), 0, 26 (32.9%) and 3 (3.8%), respectively, and that LM with metastases to the brain parenchyma was found in 42 cases (53.2%). The results of enhanced MRI examination of spinal cord in 59 cases showed that there were only enhancements of type A and C in 40 cases (67.8%) and 3 cases (5.0%), and no enhancement sign in the other 16 cases (27.2%). CONCLUSION MRI examination of brain and spinal cord will improve the detection rate of LM. The MRI features of NSCLC-LM in real world are mainly characterized by the linear enhancements of brain and spinal cord, followed by linear combined with nodular enhancement. The enhancements of type B and type D are rare in clinic. Almost half of the patients have LM and metastases to the brain parenchyma. Therefore, the differentiation of tumor metastases is needed to be paid attention to for the early diagnosis and the formulation of reasonable treatment plans.

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