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Biomedical subjects

A J Spence

Publications and source records attributed to A J Spence.

5 recordsLinked to original sources
PubMed2005

Dexamethasone treatment reduces astroglia responses to inserted neuroprosthetic devices in rat neocortex.

Microfabricated neural prosthetic devices hold great potential for increasing knowledge of brain function and treating patients with lost CNS function. Time-dependent loss of brain-device communication limits long-term use of these devices. Lost CNS function is associated with reactive responses that produce an encapsulating cellular sheath. Since early reactive responses may be associated with injuries produced at the time of device insertion, for example, vascular damage and disruption of the blood-brain barrier, we tested the effectiveness of the synthetic glucocorticoid, dexamethasone, in controlling insertion- and device-associated reactive responses. Dexamethasone (200 microg/kg) was administered as subcutaneous injections for 1 or 6 days beginning on the day of device insertion. Single shank microfabricated silicon devices were inserted into pre-motor cortex of adult rats. Reactive responses were assessed by immunohistochemistry for glial fibrillary acidic protein (astrocytes), CD11b (microglia), and laminin that labeled extracellular protein deposited around the insertion site and in association with vascular elements. Data were collected by confocal microscopy imaging of 100-microm-thick tissue slices. Reactive responses in vehicle control animals were similar to non-injected control animals. Dexamethasone treatment profoundly effected early and sustained reactive responses observed 1 and 6 weeks following device insertion, respectively. Dexamethasone treatment greatly attenuated astroglia responses, while microglia and vascular responses appeared to be increased. The 6-day treatment was more effective than the single injection regime. These results suggest that anti-inflammatory agents can be used to control reactive responses around inserted neural prosthetic devices and may provide a means to insure their long-term function.

Animals↗
PubMed2003

Brain responses to micro-machined silicon devices.

Micro-machined neural prosthetic devices can be designed and fabricated to permit recording and stimulation of specific sites in the nervous system. Unfortunately, the long-term use of these devices is compromised by cellular encapsulation. The goals of this study were to determine if device size, surface characteristics, or insertion method affected this response. Devices with two general designs were used. One group had chisel-shaped tips, sharp angular corners, and surface irregularities on the micrometer size scale. The second group had rounded corners, and smooth surfaces. Devices of the first group were inserted using a microprocessor-controlled inserter. Devices of the second group were inserted by hand. Comparisons were made of responses to the larger devices in the first group with devices from the second group. Responses were assessed 1 day and 1, 2, 4, 6, and 12 weeks after insertions. Tissues were immunochemically labeled for glial fibrillary acidic protein (GFAP) or vimentin to identify astrocytes, or for ED1 to identify microglia. For the second comparison devices from the first group with different cross-sectional areas were analyzed. Similar reactive responses were observed following insertion of all devices; however, the volume of tissue involved at early times, <1 week, was proportional to the cross-sectional area of the devices. Responses observed after 4 weeks were similar for all devices. Thus, the continued presence of devices promotes formation of a sheath composed partly of reactive astrocytes and microglia. Both GFAP-positive and -negative cells were adherent to all devices. These data indicate that device insertion promotes two responses-an early response that is proportional to device size and a sustained response that is independent of device size, geometry, and surface roughness. The early response may be associated with the amount of damage generated during insertion. The sustained response is more likely due to tissue-device interactions.

Animals↗
PubMed2003

A micromachined silicon multielectrode for multiunit recording.

A 16-channel multielectrode was used to record propagating action potentials from multiple units in the ventral nerve cord of the cricket Gryllus bimaculatus. The multielectrode was fabricated using photolithographic and bulk silicon etching techniques. The fabrication differs from standard methods in its use of deep reactive ion etching (DRIE) to form the bulk electrode structure. This technique enables the fabrication of relatively thick (>100 microm), rigid structures whose top surface can have any form of thin film electronics. The multielectrode tested in this paper consists of 16 narrow silicon bridges, 150 microm wide and 350 microm tall, spaced evenly over a centimeter, with passive rectangular gold recording sites on the top surface. The nerve cord was placed perpendicularly across the bridges. In this geometry, the nerve spans a 350 microm deep, 450 microm wide trench between each recording site, permitting adequate isolation of recording sites from each other and a platinum ground plane. Spike templates for eight neurons were formed using principle component analysis and clustering of the concatenated multichannel waveforms. Clean templates were generated from a 40 s recording of stimulus evoked activity. Conduction velocities ranged from 2.59+/-0.05 to 4.99+/-0.12 m/s. Two limitations of extracellular electrode arrays are the resolution of overlapping spikes and relation of discriminated units to known anatomy. The high density, precise positioning, and controlled impedance of recording sites achievable in microfabricated devices such as this one will aid in overcoming these limitations. The rigid devices fabricated using this process offer stable positioning of recording sites over relatively large distances (several millimeters) and are suitable for clamping or squeezing of nerve cords.

Action Potentials↗