Sandberg David I, Edgar Mark A, Souweidane Mark M
Department of Neurosurgery, Weill Medical College of Cornell University, New York, NY, USA.
J Neurosurg. 2002 May;96(5):885-91. doi: 10.3171/jns.2002.96.5.0885.
Convection-enhanced delivery (CED) can be used safely to achieve high local infusate concentrations within the brain and spinal cord. The use of CED in the brainstem has not been previously reported and may offer an alternative method for treating diffuse pontine gliomas. In the present study the authors tested CED within the rat brainstem to assess its safety and establish distribution parameters.
Eighteen rats underwent stereotactic cannula placement into the pontine nucleus oralis without subsequent infusions. Twenty rats underwent stereotactic cannula placement followed by infusion of fluorescein isothiocyanate (FITC)-dextran at a constant rate (0.1 microl/minute) until various total volumes of infusion (V(i)s) were reached: 0.5, 1, 2, and 4 microl. Additional rats underwent FITC-dextran infusion (V, 4 microl) and were observed for 48 hours (five animals) or 14 days (five animals). Serial (20-microm thick) brain sections were imaged using confocal microscopy with ultraviolet illumination, and the volume of distribution (Vd) was calculated using computer image analysis. Histological analysis was performed on adjacent sections. No animal exhibited a postoperative neurological deficit, and there was no histological evidence of tissue disruption. The Vd increased linearly (range 15.4-55.8 mm3) along with increasing Vi, with statistically significant correlations for all groups that were compared (p < 0.022). The Va/Vi ratio ranged from 14 to 30.9. The maximum cross-sectional area of fluorescence (range 9.8-20.9 mm2) and the craniocaudal extent of fluorescence (range 2.8-5.1 mm) increased with increasing Vi.
Convection-enhanced delivery can be safely applied to the rat brainstem with substantial and predictable V(d)s. This study provides the basis for investigating delivery of various candidate agents for the treatment of diffuse pontine gliomas.
对流增强递送（CED）可安全用于在脑和脊髓内实现高局部输注物浓度。此前尚未有在脑干中使用CED的报道，其可能为治疗弥漫性桥脑胶质瘤提供一种替代方法。在本研究中，作者在大鼠脑干内测试了CED，以评估其安全性并确定分布参数。
18只大鼠接受立体定向插管至脑桥核口部但随后未进行输注。20只大鼠接受立体定向插管，随后以恒定速率（0.1微升/分钟）输注异硫氰酸荧光素（FITC）-葡聚糖，直至达到不同的总输注体积（V(i)s）：0.5、1、2和4微升。另外的大鼠接受FITC-葡聚糖输注（V，4微升），并观察48小时（5只动物）或14天（5只动物）。使用共聚焦显微镜在紫外光照射下对连续的（20微米厚）脑切片进行成像，并使用计算机图像分析计算分布体积（Vd）。对相邻切片进行组织学分析。没有动物出现术后神经功能缺损，也没有组织破坏的组织学证据。Vd随着Vi的增加呈线性增加（范围为15.4 - 55.8立方毫米），所有比较组之间均具有统计学显著相关性（p < 0.022）。Va/Vi比值范围为14至30.9。荧光的最大横截面积（范围为9.8 - 20.9平方毫米）和荧光的头尾范围（范围为2.8 - 5.1毫米）随着Vi的增加而增加。
对流增强递送可安全应用于大鼠脑干，具有可观且可预测的V(d)s。本研究为研究用于治疗弥漫性桥脑胶质瘤的各种候选药物的递送提供了基础。
