Construction and implantation of a microinfusion system for sustained delivery of neuroactive agents.
Experimental protocols used for chronic infusion of neuroactive agents within regions of the brain often utilize a mini-osmotic pump system. Agents are commonly delivered via a stainless steel cannula with a diameter of 0.30 mm or greater. Systems utilizing a cannula of this caliber may impose trauma to the area of interest resulting in architectural damage, thereby compromising structural integrity and normal functioning. As neuroscience inquiry becomes more sophisticated, investigation of brain structures and circuitry requires improved levels of accuracy and higher resolution. We have developed a method for the preparation and implantation of a chronic infusion system within the brain utilizing a borosilicate microcannula with a tip diameter of 50 microm. This technique reduces damage to the local environment and diminishes reactive gliosis at the site of infusion. The configuration of the microinfusion system is also able to conform to the surface of the animal's skull, precluding the need for large cranial pedestals, and thus facilitating closure of the scalp incision and reducing the risk of infection. We demonstrate reliable sustained delivery of a dye having a representative molecular weight using an in vitro model and in vivo studies in rats.
Cunningham
Miles Gregory
MG
Laboratory for Neural Reconstruction, McLean Hospital, Program in Neuroscience and Department of Psychiatry, Harvard Medical School, Boston, MA 02478, United States. mcunningham@mclean.harvard.edu
Ames
Heather Marion
HM
Donalds
Rachael Ann
RA
Benes
Francine Mary
FM
D000818:Animals; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000209:etiology / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects / Q000295:instrumentation*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007260:Infusion Pumps; D015918:Infusion Pumps, Implantable / Q000009:adverse effects / Q000592:standards; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012394:Rosaniline Dyes / Q000378:metabolism; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D012394:Rosaniline Dyes; C035906:Fast Green