The use of lipid-coated microbubbles as a delivery agent of 7beta-hydroxycholesterol in a radiofrequency lesion in the rat brain.
OBJECTIVE
This laboratory has previously described the aggregation of intravenously administered lipid-coated microbubbles (LCM) around tumors and areas of injury. 7Beta-hydroxycholesterol has been used to inhibit astrocytic proliferation in nervous system injury models. The compound has been given by direct infusion, by epidural catheter, or in liposomes (delivered stereotactically to the injury site). In this article, we report the use of LCM to deliver 7beta-hydroxycholesterol to a radiofrequency injury site in the rat cerebrum.


METHODS
First, the ability of LCM to target the thermal lesion in the rat brain was characterized using a lipid-soluble fluorescent dye 3,3-dioctadecyloxacarbocyanine perchlorate. Then, the effectiveness of this delivery system in suppression of glial proliferation was measured by glial fibrillary acidic protein immunoreactivity.


RESULTS
Glial fibrillary acidic protein immunoreactivity was significantly reduced when 7beta-hydroxycholesterol was administered via LCM but not alone, suggesting that astrocytic proliferation would correspondingly be diminished.


CONCLUSIONS
LCM were assessed as a delivery vehicle for 7beta-hydroxycholesterol in a rat brain radiofrequency lesion and found to be efficient in reducing astrogliosis, as measured by glial fibrillary acidic protein immunoreactivity.
Wakefield
A E
AE
Department of Surgery, University of Connecticut Health Center, Farmington, USA.
Ho
S Y
SY
Li
X G
XG
D'Arrigo
J S
JS
Simon
R H
RH
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002232:Carbocyanines; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000517:prevention & control*; D006888:Hydroxycholesterols / Q000008:administration & dosage* / Q000627:therapeutic use; D007150:Immunohistochemistry; D008055:Lipids; D008863:Microspheres; D011846:Radio Waves; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
D002232:Carbocyanines; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D006888:Hydroxycholesterols; D008055:Lipids; C011724:cholest-5-en-3 beta,7 alpha-diol; C098044:3,3'-dioctadecyloxacarbocyanine