scholarly journals Mechanical flexibility reduces the foreign body response to long-term implanted microelectrodes in rabbit cortex

2016 ◽  
Author(s):  
H S Sohal ◽  
G J Clowry ◽  
A Jackson ◽  
A O’Neill ◽  
S N Baker
Keyword(s):  
Cell Activation ◽  
Foreign Body Response ◽  
Mechanical Trauma ◽  
Flexible Electrode ◽  
Implanted Electrodes ◽  
Glial Cell Activation ◽  
Flexible Probe ◽  
The Brain ◽  
Body Response

AbstractMicromotion between the brain and implanted electrodes is a major contributor to the failure of invasive microelectrodes. Movements of the electrode tip cause recording instabilities while spike amplitudes decline over the weeks/months post-implantation due to glial cell activation caused by sustained mechanical trauma. We compared the glial response over a 26-96 week period following implantation in the rabbit cortex of microwires and a novel flexible electrode. Horizontal sections were used to obtain a depth profile of the radial distribution of microglia, astrocytes and neurofilament. We found that the flexible electrode was associated with decreased gliosis compared to the microwires over these long indwelling periods. This was in part due to a decrease in overall microgliosis and enhanced neuronal density around the flexible probe, especially at longer periods of implantation.

scholarly journals Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Seongjun Park ◽  
Hyunwoo Yuk ◽  
Ruike Zhao ◽  
Yeong Shin Yim ◽  
Eyob W. Woldeghebriel ◽  
...  
Keyword(s):  
Foreign Body ◽  
Brain Regions ◽  
Foreign Body Response ◽  
Behavioral Studies ◽  
Hydrogel Matrix ◽  
Underlying Mechanisms ◽  
Hybrid Devices ◽  
The Brain ◽  
Body Response

AbstractTo understand the underlying mechanisms of progressive neurophysiological phenomena, neural interfaces should interact bi-directionally with brain circuits over extended periods of time. However, such interfaces remain limited by the foreign body response that stems from the chemo-mechanical mismatch between the probes and the neural tissues. To address this challenge, we developed a multifunctional sensing and actuation platform consisting of multimaterial fibers intimately integrated within a soft hydrogel matrix mimicking the brain tissue. These hybrid devices possess adaptive bending stiffness determined by the hydration states of the hydrogel matrix. This enables their direct insertion into the deep brain regions, while minimizing tissue damage associated with the brain micromotion after implantation. The hydrogel hybrid devices permit electrophysiological, optogenetic, and behavioral studies of neural circuits with minimal foreign body responses and tracking of stable isolated single neuron potentials in freely moving mice over 6 months following implantation.

scholarly journals Mechanically Matched Silicone Brain Implants Reduce Brain Foreign Body Response

2020 ◽  
Author(s):  
Edward Zhang ◽  
Alia Alameri ◽  
Jean-Pierre Clement ◽  
Andy Ng ◽  
Timothy E Kennedy ◽  
...  
Keyword(s):  
Foreign Body ◽  
Neurological Disorders ◽  
Foreign Body Response ◽  
Brain Implants ◽  
Rat Neocortex ◽  
The Brain ◽  
Post Implantation ◽  
Body Response ◽  
Clinical Adoption

Brain implants are increasingly used to treat neurological disorders and diseases. However, the brain foreign body response (FBR) elicited by implants affects neuro-electrical transduction and long-term reliability limiting their clinical adoption. The mismatch in Young's modulus between silicon implants (~180 GPa) and brain tissue (~1-30 kPa) exacerbates the FBR resulting in the development of flexible implants from polymers such as polyimide (~1.5-2.5 GPa). However, a stiffness mismatch of at least two orders of magnitude remains. Here, we introduce (i) the first mechanically matched brain implant (MMBI) made from silicone (~20 kPa), (ii) new microfabrication methods, and (iii) a novel dissolvable sugar shuttle to reliably implant MMBIs. MMBIs were fabricated via vacuum-assisted molding using sacrificial sugar molds and were then encased in sugar shuttles that dissolved within 2 min after insertion into rat brains. Sections of rat neocortex implanted with MMBIs, PDMS implants, and silicon implants were analyzed by immunohistochemistry 3 and 9-weeks post-implantation. MMBIs resulted in significantly higher neuronal density and lower FBR within 50 μm of the tissue-implant interface compared to PDMS and silicon implants suggesting that materials mechanically matched to brain further minimize the FBR and could contribute to better implant functionality and long-term reliability.

Examinations of a new long-term degradable electrospun polycaprolactone scaffold in three rat abdominal wall models

2017 ◽  
Vol 31 (7) ◽  
pp. 1077-1086 ◽  
Author(s):  
Hanna Jangö ◽  
Søren Gräs ◽  
Lise Christensen ◽  
Gunnar Lose
Keyword(s):  
Pelvic Organ Prolapse ◽  
Foreign Body ◽  
Abdominal Wall ◽  
Muscle Fiber ◽  
Pelvic Organ ◽  
Foreign Body Response ◽  
Heavy Load ◽  
Tissue Construct ◽  
Body Response

Alternative approaches to reinforce native tissue in reconstructive surgery for pelvic organ prolapse are warranted. Tissue engineering combines the use of a scaffold with the regenerative potential of stem cells and is a promising new concept in urogynecology. Our objective was to evaluate whether a newly developed long-term degradable polycaprolactone scaffold could provide biomechanical reinforcement and function as a scaffold for autologous muscle fiber fragments. We performed a study with three different rat abdominal wall models where the scaffold with or without muscle fiber fragments was placed (1) subcutaneously (minimal load), (2) in a partial defect (partial load), and (3) in a full-thickness defect (heavy load). After 8 weeks, no animals had developed hernia, and the scaffold provided biomechanical reinforcement, even in the models where it was subjected to heavy load. The scaffold was not yet degraded but showed increased thickness in all groups. Histologically, we found a massive foreign body response with numerous large giant cells intermingled with the fibers of the scaffold. Cells from added muscle fiber fragments could not be traced by PKH26 fluorescence or desmin staining. Taken together, the long-term degradable polycaprolactone scaffold provided biomechanical reinforcement by inducing a marked foreign-body response and attracting numerous inflammatory cells to form a strong neo-tissue construct. However, cells from the muscle fiber fragments did not survive in this milieu. Properties of the new neo-tissue construct must be evaluated at the time of full degradation of the scaffold before its possible clinical value in pelvic organ prolapse surgery can be evaluated.

scholarly journals Investigating the convergent mechanisms between Major Depressive Disorder and Parkinson’s disease

2020 ◽  
Author(s):  
Angela A Tran ◽  
Myra De Smet ◽  
Gary D. Grant ◽  
Tien K. Khoo ◽  
Dean L Pountney
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Cell Activation ◽  
Glutamate Excitotoxicity ◽  
Major Depressive ◽  
Glial Cell Activation ◽  
Underlying Mechanisms ◽  
The Brain

Major depressive disorder (MDD) affects more than cognition, having a temporal relationship with neuroinflammatory pathways of Parkinson’s disease (PD). Although this association is supported by epidemiological and clinical studies, the underlying mechanisms are unclear. Microglia and astrocytes play crucial roles in the pathophysiology of both MDD and PD. In PD, these cells can be activated by misfolded forms of the protein α-synuclein to release cytokines that can interact with multiple different physiological processes to produce depressive symptoms, including monoamine transport and availability, the hypothalamus-pituitary axis, and neurogenesis. In MDD, glial cell activation can be induced by peripheral inflammatory agents that cross the blood brain barrier and/or c-Fos signaling from neurons. The resulting neuroinflammation can cause neurodegeneration due to oxidative stress and glutamate excitotoxicity, contributing to PD pathology. Astrocytes are another major link due to their recognised role in the glymphatic clearance mechanism. Research suggesting that MDD causes astrocytic destruction or structural atrophy highlight the possibility that accumulation of α-synuclein in the brain is facilitated as the brain cannot adequately clear the protein aggregates. This review examines research into the overlapping pathophysiology of MDD and PD with particular focus on the roles of glial cells and neuroinflammation.

Long-term evaluation of adhesion formation and foreign body response to three new meshes

2014 ◽  
Vol 29 (8) ◽  
pp. 2251-2259 ◽  
Author(s):  
R. R. M. Vogels ◽  
K. W. Y. van Barneveld ◽  
J. W. A. M. Bosmans ◽  
G. Beets ◽  
M. J. J. Gijbels ◽  
...  
Keyword(s):  
Foreign Body ◽  
Adhesion Formation ◽  
Foreign Body Response ◽  
Term Evaluation ◽  
Body Response

Long-term pericardial catheterization is associated with minimum foreign-body response

2007 ◽  
Vol 70 (2) ◽  
pp. 221-227 ◽  
Author(s):  
Carlo R. Bartoli ◽  
Ichiro Akiyama ◽  
John J. Godleski ◽  
Richard L. Verrier
Keyword(s):  
Foreign Body ◽  
Foreign Body Response ◽  
Body Response

The acute and the long-term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activation

2005 ◽  
Vol 22 (2) ◽  
pp. 317-330 ◽  
Author(s):  
Mahmoud M. Iravani ◽  
Clement C. M. Leung ◽  
Mona Sadeghian ◽  
Claire O. Haddon ◽  
Sarah Rose ◽  
...  
Keyword(s):  
Glial Cell ◽  
Cell Activation ◽  
Long Term Effects ◽  
Glial Cell Activation ◽  
Dopaminergic Dysfunction

scholarly journals A Spatial Transcriptomics Study of the Brain-Electrode Interface in Rat Motor Cortex

2021 ◽  
Author(s):  
Quentin A. Whitsitt ◽  
Bella Patel ◽  
Brad Hunt ◽  
Erin K. Purcell
Keyword(s):  
Gene Expression ◽  
Foreign Body ◽  
Motor Cortex ◽  
Rna Binding ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Foreign Body Response ◽  
Electrode Implantation ◽  
Implanted Electrodes ◽  
The Brain

AbstractThe study of the foreign body reaction to implanted electrodes in the brain is an important area of research for the future development of neuroprostheses and experimental electrophysiology. After electrode implantation in the brain, microglial activation, reactive astrogliosis, and neuronal cell death create an environment immediately surrounding the electrode that is significantly altered from its homeostatic state. To uncover physiological changes potentially affecting device function and longevity, spatial transcriptomics was implemented in this preliminary study to identify changes in gene expression driven by electrode implantation. This RNA-sequencing technique (10x Genomics, Visium) uses spatially coded, RNA-binding oligonucleotides on a microscope slide to spatially identify each sequencing read. For these experiments, sections of rat motor cortex implanted with Michigan-style silicon electrodes were mounted on the Visium slide for processing. Each tissue section was labeled for neurons and astrocytes using immunohistochemistry to provide a spatial reference for mapping each sequencing read relative to the device tract. Results from rat motor cortex at 24 hours, 1 week, and 6 weeks post implantation showed up to 5811 differentially expressed genes between implanted and non-implanted tissue sections. Many of these genes are related to biological mechanisms previously reported in studies of the foreign body response to implanted electrodes, while others are novel to this study. These results will provide a foundation for future work to both improve and measure the effects of gene expression on the long-term stability of recordings from implanted electrodes in the brain. Ongoing work will expand on these initial observations as we gain a better understanding of the dynamic, molecular changes taking place in the brain in response to electrode implantation.

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