Wakefield A E, Ho S Y, Li X G, D'Arrigo J S, Simon R H
Department of Surgery, University of Connecticut Health Center, Farmington, USA.
Neurosurgery. 1998 Mar;42(3):592-8. doi: 10.1097/00006123-199803000-00029.
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.
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.
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.
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.
本实验室先前已描述了静脉注射的脂质包被微泡(LCM)在肿瘤及损伤区域周围的聚集情况。7β-羟基胆固醇已被用于抑制神经系统损伤模型中的星形胶质细胞增殖。该化合物通过直接注射、硬膜外导管给药或脂质体给药(立体定向输送至损伤部位)。在本文中,我们报告了使用LCM将7β-羟基胆固醇输送至大鼠大脑的射频损伤部位。
首先,使用脂溶性荧光染料高氯酸3,3-二辛基氧杂羰花青来表征LCM靶向大鼠脑内热损伤的能力。然后,通过胶质纤维酸性蛋白免疫反应性来测量该递送系统在抑制胶质细胞增殖方面的有效性。
当通过LCM而非单独给药7β-羟基胆固醇时,胶质纤维酸性蛋白免疫反应性显著降低,这表明星形胶质细胞增殖将相应减少。
在大鼠脑射频损伤中,LCM被评估为7β-羟基胆固醇的递送载体,并且通过胶质纤维酸性蛋白免疫反应性测量发现其在减少星形胶质细胞增生方面是有效的。