Thomale U W, Tyler B, Renard V M, Dorfman B, Guarnieri M, Haberl H E, Jallo G I
Selbständiger Arbeitsbereich Pädiatrische Neurochirurgie, Charité, Campus Virchow Klinikum, Universitätsmedizin Berlin, Augustenburgr Platz 1, 13353, Berlin, Germany.
Childs Nerv Syst. 2009 Jan;25(1):21-8. doi: 10.1007/s00381-008-0684-7. Epub 2008 Aug 9.
Technical aspects of local chemotherapy in inoperable brainstem gliomas by convection-enhanced delivery (CED) are still under experimental considerations. In this study, we characterize the feasibility of multiple cannula placements in the rat brainstem.
In 38 male Fisher rats, up to three guided screws were positioned in burr holes paramedian at 2.5 mm anterior and posterior to as well as at the lambdoid suture. Using Alzettrade mark pumps (1 microl/h flow rate over 7 days) either vehicle (5% dextrose) or 0.1 mg carboplatin was delivered via one, two, or three cannulas, respectively. During cannula insertion, electrocardiogram and respiratory rate was monitored. All rats were subsequently evaluated neurologically for 8 days. For drug distribution in coronal sections, the brain tissue concentration of platinum was measured. HE staining was used to evaluate the local site of drug delivery. Heart and respiratory rate remained within normal range during surgical procedure. Neurological scoring showed only mild neurological impairment in the groups receiving two or three cannulas, which resolved after vehicle delivery. However, after carboplatin delivery, this deficit remained unchanged. Drug distribution was more homogeneous in the three cannula group. Histological slices visualized edematous changes at the sight of cannula placement.
The unilateral application of up to three cannulas in the brainstem of rats for local drug delivery studies is feasible. The remaining neurological deficit in carboplatin-treated animals underlines the need of low toxicity drugs for CED in the brainstem.
通过对流增强递送（CED）对无法手术的脑干胶质瘤进行局部化疗的技术方面仍在实验研究中。在本研究中，我们描述了在大鼠脑干中多次插管的可行性。
在38只雄性Fisher大鼠中，在位于前、后2.5毫米处以及人字缝的旁正中钻孔中放置多达三个导向螺钉。分别通过一根、两根或三根插管使用Alzet商标泵（7天内流速为1微升/小时）输送载体（5%葡萄糖）或0.1毫克卡铂。在插管过程中，监测心电图和呼吸频率。随后对所有大鼠进行8天的神经学评估。为了在冠状切片中观察药物分布，测量脑组织中的铂浓度。采用苏木精-伊红（HE）染色评估药物递送的局部部位。手术过程中心率和呼吸频率保持在正常范围内。神经学评分显示，接受两根或三根插管的组仅出现轻度神经功能损害，在输注载体后症状缓解。然而，输注卡铂后，这种缺陷仍未改变。三根插管组的药物分布更均匀。组织学切片显示插管部位出现水肿变化。
在大鼠脑干单侧应用多达三根插管进行局部药物递送研究是可行的。卡铂治疗动物中残留的神经功能缺陷凸显了在脑干进行CED时需要低毒性药物。
