Culver B, Inzana K, Jones J, Troy G, Kroll R, Culver B, Jortner B
Department of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061, USA.
Am J Vet Res. 1998 Nov;59(11):1503-10.
To design a repeatable technique for reversible, hyperosmotic blood-brain barrier disruption (BBBD) in dogs and evaluate clinical effects of multiple BBBD.
10 healthy adult dogs.
Using fluoroscopic guidance, an arterial catheter was directed into the internal carotid artery via the femoral artery of 10 dogs. Blood-brain barrier disruption was achieved in 5 dogs, using intracarotid infusion of mannitol. Five control dogs received only saline solution. After recovery, dogs were monitored for clinical signs of disease before a second, nonsurvival procedure was performed 2 to 3 weeks later. BBBD was estimated, using computed tomographic (CT) densitometry values, as well as Evan's blue dye staining on necropsy specimens.
Seven dogs completed the entire study. Two treatment dogs were lost after the first infusion because of deteriorating neurologic function attributed to CNS edema and increased intracranial pressure. One control dog was lost because of vessel wall damage during catheterization. The remaining dogs had only transient neurologic, ocular, and vasculature injuries. Successful BBBD was documented in all treated dogs by use of CT and Evan's blue dye evaluation.
Repeated catheterization of the internal carotid artery and disruption of the blood- brain barrier is possible in dogs.
Refinement of this technique would be useful not only for improved delivery of chemotherapeutic agents in patients with brain tumors, but also would allow further investigation of new treatments involving genetically engineered retroviruses and monoclonal antibodies.
设计一种可重复的技术，用于犬可逆性、高渗性血脑屏障破坏（BBBD），并评估多次BBBD的临床效果。
10只健康成年犬。
在荧光透视引导下，通过10只犬的股动脉将动脉导管插入颈内动脉。5只犬通过颈内动脉输注甘露醇实现血脑屏障破坏。5只对照犬仅接受盐溶液。恢复后，监测犬的疾病临床症状，2至3周后进行第二次非存活手术。使用计算机断层扫描（CT）密度测定值以及尸检标本上的伊文思蓝染料染色评估BBBD。
7只犬完成了整个研究。2只治疗犬在首次输注后因中枢神经系统水肿和颅内压升高导致神经功能恶化而死亡。1只对照犬因插管过程中血管壁损伤而死亡。其余犬仅出现短暂的神经、眼部和血管损伤。通过CT和伊文思蓝染料评估，所有治疗犬均记录到成功的BBBD。
犬重复进行颈内动脉插管和血脑屏障破坏是可行的。
改进该技术不仅有助于改善脑肿瘤患者化疗药物的递送，还能进一步研究涉及基因工程逆转录病毒和单克隆抗体的新治疗方法。
