Suppression of excitotoxicity and foreign body response by memantine in chronic cannula implantation into the rat brain

Hayn, Linda; Koch, Michael

doi:10.1016/j.brainresbull.2015.08.001

Cited by 9 publications

(11 citation statements)

References 66 publications

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“…Neuronal cell death around a chronically indwelling cannula was also found previously and is in line with studies that revealed neuronal ‘die‐back’ zones around an implant . The decreased neuronal density within the first 50 μm around the implant in control animals in this study is accompanied by the formation of a glial scar, which is suggested to occur faster than a re‐growth of neuronal processes .…”

Section: Discussionsupporting

confidence: 91%

“…Each forelimb movement during a successful hit in the skilled reaching box consists of 12 movement subelements: Orientation , limb lift , digits flexion , aim , advance , digit extension and opening , pronation , grasp , supination I , supination II , release , and replace . The first five attempts on each test day before and after the surgery were analysed for these 12 subelements and rated using a three‐point scale.…”

Section: Methodsmentioning

confidence: 99%

“…It has been suggested to be neuroprotective and neurorestorative via the inhibition of inducible NO‐synthase, the reduction of pro‐inflammatory molecules such as TNFα, IL‐1β or NO and the increase of anti‐inflammatory molecules such as TGF‐β or IL‐10, as well as by a decrease of glutamatergic neurotoxicity by inhibiting the NMDA‐induced activation of p38 MAPK in microglial cells . The specific contribution of glutamate‐mediated excitotoxicity to the foreign body response was shown previously using the uncompetitive NMDA receptor antagonist memantine . The extent of tissue damage after cannula implantation in the caudal forelimb area (CFA) of the motor cortex (M1) of rats was examined on the behavioural level using the skilled reaching task before and once weekly after cannula implantation.…”

Section: Introductionmentioning

confidence: 93%

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Reduction of the foreign body response and neuroprotection by apyrase and minocycline in chronic cannula implantation in the rat brain

Hayn

Deppermann

Koch

2017

Clin Exp Pharma Physio

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Implantation of electrodes or cannulae into the brain is accompanied by a tissue response referred to as foreign body response. Adenosine triphosphate (ATP) is one of the signalling molecules released by injured cells which mediate the chemoattraction of microglial cells. The constitutive release of pro-inflammatory and cytotoxic substances by microglial cells in chronic implants exacerbates neuronal cell death and the immune response. This study aimed to interfere with the initial events of the foreign body response in order to mitigate neurotoxicity and inflammation. For this purpose, the ATP-hydrolysing enzyme apyrase and the antibiotic minocycline with a broad range of anti-inflammatory, anti-apoptotic and glutamate-antagonist properties were locally infused during cannula implantation in the caudal forelimb area of the motor cortex in Lister Hooded rats. The rats' motor performance was assessed in a skilled reaching task and the distribution of neurons and glial cells in the vicinity of the implant was examined 2 and 6 weeks post-implantation. Apyrase as well as minocycline increased the number of surviving neurons and reduced microglial activation. Moreover, minocycline improved the motor performance and, additionally, caused a temporary reduction in astrogliosis, suggesting it as a possible therapeutic candidate to improve the biocompatibility of chronic brain implants.

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Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

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Reduction of the foreign body response and neuroprotection by apyrase and minocycline in chronic cannula implantation in the rat brain

Hayn

Deppermann

Koch

2017

Clin Exp Pharma Physio

Self Cite

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“…In the current study, animals completed a ladder test similar to the setup outlined by Hayn and Koch (Fig. 5 ) 49 . Ladder tests have been used in previous studies to test for paw placement, stepping, and limb coordination 50 , and to tease out impairments in brain injury models such as stroke 50 – 52 .…”

Section: Discusssionmentioning

confidence: 99%

Microelectrode implantation in motor cortex causes fine motor deficit: Implications on potential considerations to Brain Computer Interfacing and Human Augmentation

Goss-Varley

Dona

McMahon

et al. 2017

Sci Rep

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Intracortical microelectrodes have shown great success in enabling locked-in patients to interact with computers, robotic limbs, and their own electrically driven limbs. The recent advances have inspired world-wide enthusiasm resulting in billions of dollars invested in federal and industrial sponsorships to understanding the brain for rehabilitative applications. Additionally, private philanthropists have also demonstrated excitement in the field by investing in the use of brain interfacing technologies as a means to human augmentation. While the promise of incredible technologies is real, caution must be taken as implications regarding optimal performance and unforeseen side effects following device implantation into the brain are not fully characterized. The current study is aimed to quantify any motor deficit caused by microelectrode implantation in the motor cortex of healthy rats compared to non-implanted controls. Following electrode insertion, rats were tested on an open-field grid test to study gross motor function and a ladder test to study fine motor function. It was discovered that rats with chronically indwelling intracortical microelectrodes exhibited up to an incredible 527% increase in time to complete the fine motor task. This initial study defines the need for further and more robust behavioral testing of potential unintentional harm caused by microelectrode implantation.

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“…To gain access to more deep brain regions, researchers remove superficial tissue 3 or employ implantable optics, such as gradient index (GRIN) lenses and prisms 4 – 6 Such implants can damage or obliterate more superficial tissue and, given dense local connectivity, may jeopardize local network dynamics in the tissue surrounding the implant 7 – 9 …”

Section: Introductionmentioning

confidence: 99%

Extracting individual neural activity recorded through splayed optical microfibers

et al. 2019

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Abstract.Previously introduced bundles of hundreds or thousands of microfibers have the potential to extend optical access to deep brain regions, sampling fluorescence activity throughout a three-dimensional volume. Each fiber has a small diameter (8 μm) and follows a path of least resistance, splaying during insertion. By superimposing the fiber sensitivity profile for each fiber, we model the interface properties for a simulated neural population. Our modeling results suggest that for small (<200) bundles of fibers, each fiber will collect fluorescence from a small number of nonoverlapping neurons near the fiber apertures. As the number of fibers increases, the bundle delivers more uniform excitation power to the region, moving to a regime where fibers collect fluorescence from more neurons and there is greater overlap between neighboring fibers. Under these conditions, it becomes feasible to apply source separation to extract individual neural contributions. In addition, we demonstrate a source separation technique particularly suited to the interface. Our modeling helps establish performance expectations for this interface and provides a framework for estimating neural contributions under a range of conditions.

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Suppression of excitotoxicity and foreign body response by memantine in chronic cannula implantation into the rat brain

Cited by 9 publications

References 66 publications

Reduction of the foreign body response and neuroprotection by apyrase and minocycline in chronic cannula implantation in the rat brain

Reduction of the foreign body response and neuroprotection by apyrase and minocycline in chronic cannula implantation in the rat brain

Microelectrode implantation in motor cortex causes fine motor deficit: Implications on potential considerations to Brain Computer Interfacing and Human Augmentation

Extracting individual neural activity recorded through splayed optical microfibers

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