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首页> 外文期刊>Neurosurgery >Intracerebral clysis in a rat glioma model.
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Intracerebral clysis in a rat glioma model.

机译：大鼠脑胶质瘤模型中的脑内裂解。

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OBJECTIVE: Intracerebral clysis (ICC) is a new term we use to describe convection-enhanced microinfusion into the brain. This study establishes baseline parameters for preclinical, in vivo, drug investigations using ICC in a rat glioma model. METHODS: Intracranial pressure was measured, with an intraparenchymal fiber-optic catheter, in male Fischer rats 10, 15, 20, and 25 days after implantation of C6 glioma cells in the right frontal lobe (n = 80) and in control rats without tumor (n = 20), before and during ICC. A 25% albumin solution (100 microl) was infused through an intratumoral catheter at 0.5, 1.0, 2.0, 3.0, and 4.0 microl/min. Infusate distribution was assessed by infusion of fluorescein isothiocyanate-dextran (Mr 20,000), using the aforementioned parameters (n = 36). Brains were sectioned and photographed under ultraviolet light, and distribution was calculated by computer analysis (NIH Image for Macintosh). Safe effective drug distribution was demonstrated by measuring tumor sizes and apoptosis in animals treated with N,N'-bis(2-chloroethyl)-N-nitrosourea via ICC, compared with untreated controls. Magnetic resonance imaging noninvasively confirmed tumor growth before treatment. RESULTS: Intracranial pressure increased with tumor progression, from 5.5 mm Hg at baseline to 12.95 mm Hg on Day 25 after tumor cell implantation. Intracranial pressure during ICC ranged from 5 to 21 mm Hg and was correlated with increasing infusion volumes and increasing rates of infusion. No toxicity was observed, except at the higher ends of the tumor size and volume ranges. Fluorescein isothiocyanate-dextran distribution was greater with larger infusion volumes (30 microl versus 10 microl, n = 8, P < 0.05). No significant differences in distribution were observed when different infusion rates were compared while the volume was kept constant. At tolerated flow rates, the volumes of distribution were sufficient to promote adequate drug delivery to tumors. N,N'-Bis(2-chloroethyl)-N-nitrosourea treatment resulted in significant decreases in tumor size, compared with untreated controls. CONCLUSION: The C6 glioma model can be easily modified to study aspects of interstitial delivery via ICC and the application of ICC to the screening of potential antitumor agents for safety and efficacy.
机译：目的：脑内裂解（ICC）是我们用来描述对流增强的向大脑微输注的新术语。这项研究建立了在大鼠神经胶质瘤模型中使用ICC进行临床前，体内药物研究的基线参数。方法：在C6神经胶质瘤细胞植入右额叶（n = 80）后10天，15天，20天和25天，使用实质内光纤导管测量雄性Fischer大鼠的颅内压和无肿瘤的对照大鼠（n = 20），在ICC之前和期间。通过肿瘤内导管以0.5、1.0、2.0、3.0和4.0微升/分钟的速度注入25％的白蛋白溶液（100微升）。使用上述参数（n = 36）通过注入异硫氰酸荧光素（Mr 20,000）评估输注液分布。将脑切成薄片并在紫外线下拍照，然后通过计算机分析（Macintosh的NIH Image）计算分布。与未治疗的对照组相比，通过测量经ICC N，N'-双（2-氯乙基）-N-亚硝基脲治疗的动物的肿瘤大小和细胞凋亡，证明了安全有效的药物分布。磁共振成像在治疗前无创地确认了肿瘤的生长。结果：颅内压随肿瘤进展而增加，从基线时的5.5 mm Hg上升到肿瘤细胞植入后第25天的12.95 mm Hg。 ICC期间的颅内压范围为5至21毫米汞柱，并且与输注量的增加和输注速率的增加相关。除了在肿瘤大小和体积范围的较高端，没有观察到毒性。荧光素异硫氰酸酯-右旋糖酐的分布更大，输液量更大（30微升对10微升，n = 8，P <0.05）。当比较不同的输注速率而体积不变时，没有观察到分布的显着差异。在容许的流速下，分布的体积足以促进足够的药物递送至肿瘤。与未治疗的对照组相比，N，N'-双（2-氯乙基）-N-亚硝基脲治疗可导致肿瘤大小显着减少。结论：可以容易地修改C6胶质瘤模型，以研究通过ICC进行间质递送的方面，以及ICC在筛选潜在抗肿瘤药的安全性和有效性方面的应用。

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