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

• Published in: Experimental neurology Vol. 194; no. 2; pp. 289 - 300
• Main Authors: Spataro, L., Dilgen, J., Retterer, S., Spence, A.J., Isaacson, M., Turner, J.N., Shain, W.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-08-2005; Elsevier
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Astrocytes - drug effects; Astrocytes - physiology; Astroglia; Biological and medical sciences; CD11 Antigens - metabolism; Dexamethasone; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Down-Regulation - drug effects; Down-Regulation - physiology; Electrodes, Implanted - adverse effects; Encephalitis - drug therapy; Encephalitis - etiology; Encephalitis - prevention & control; Glial Fibrillary Acidic Protein - metabolism; Gliosis - drug therapy; Gliosis - etiology; Gliosis - prevention & control; Immunomodulators; Laminin - metabolism; Male; Medical sciences; Microcirculation - drug effects; Microcirculation - pathology; Microcirculation - physiopathology; Microglia - drug effects; Microglia - physiology; Neocortex; Neocortex - drug effects; Neocortex - physiopathology; Neocortex - surgery; Neurosurgery; Pharmacology. Drug treatments; Prostheses and Implants - adverse effects; Rats; Rats, Sprague-Dawley; Skull, brain, vascular surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Time Factors; Treatment Outcome; Neocortex; Dexamethasone; Astroglia; Immunohistochemistry; Motor pathway; Rat; Neuroglia; Central nervous system; Confocal microscopy; Blood brain barrier; Glucocorticoid; Encephalon; Laminin; Motor cortex; Silicon; Human; Subcutaneous; Glial fibrillary acidic protein; Rodentia; Single dose; Neuroprosthesis; Astrocyte; Long term; Microglia; Vertebrata; Mammalia; Treatment; Animal
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2004.08.037

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 μg/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-μm-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.