Sato S, Kawase T, Harada S, Takayama H, Suga S
Department of Neurosurgery, Keio University, Tokyo, Japan.
Acta Neurochir (Wien). 1998;140(11):1135-41; disc 1141-2. doi: 10.1007/s007010050227.
Reversible opening of the blood-brain barrier (BBB) has been used to increase delivery of chemotherapeutic agents into brain tumours, but it is complicated and requires general anaesthesia. Without affecting the normal BBB, and avoiding the complications of BBB modification by hyperosmotic solution, we tried an adequate minimal BBB disruption in brain tumours. Although the effect of BBB disruption on normal brain has been described, there are no reports of the effect of an impaired BBB on microcirculation. In this study, four patients underwent surgical resection of a glioblastoma multiforme (GM; n = 1), astrocytoma (n = 2), or metastatic brain tumour (n = 1). Epicerebral microcirculation was observed in the operative field. Serial fluorescein microangiograms of the tumour and peritumoural area were obtained before and after BBB disruption was introduced intra-operatively by retrograde infusion of mannitol introducing a catheter via the temporal superficial artery back to the carotid bifurcation. On the initial microangiogram, staining by the fluorescein dye was observed in the GM and metastatic tumour but not in the astrocytoma; no extravasation of fluorescein dye was observed in the peritumoural areas. After BBB disruption, fluorescein perfusion increased and extravasation of fluorescein dye from the venules was observed in the GM and the metastatic tumour and in the peritumoural area of both lesions; BBB disruption started from venules in the peritumoural area without affecting the normal brain. However, such effects were not observed in the astrocytomas after BBB disruption nor in normal brain tissue in any patient. It appears that the integrity of the BBB is less stable in the peritumoural area of GM and metastatic brain tumours than it is in astrocytomas or normal brain. Osmotic BBB disruption may offer a method for achieving global delivery of therapeutic agents to brain tumours and peritumoural areas.
血脑屏障（BBB）的可逆性开放已被用于增加化疗药物向脑肿瘤的递送，但该方法复杂且需要全身麻醉。在不影响正常血脑屏障且避免高渗溶液改变血脑屏障所带来并发症的情况下，我们尝试在脑肿瘤中进行适度的最小程度血脑屏障破坏。尽管已有关于血脑屏障破坏对正常脑影响的描述，但尚无关于受损血脑屏障对微循环影响的报道。在本研究中，4例患者接受了多形性胶质母细胞瘤（GM；n = 1）、星形细胞瘤（n = 2）或脑转移瘤（n = 1）的手术切除。在手术区域观察大脑表面微循环。在术中通过经颞浅动脉将导管逆行插入至颈动脉分叉处并注入甘露醇进行血脑屏障破坏前后，获取肿瘤及瘤周区域的系列荧光素微血管造影图像。在最初的微血管造影图像上，在GM和转移瘤中观察到荧光素染料染色，但在星形细胞瘤中未观察到；在瘤周区域未观察到荧光素染料外渗。血脑屏障破坏后，在GM和转移瘤以及两个病变的瘤周区域均观察到荧光素灌注增加且荧光素染料从小静脉外渗；血脑屏障破坏始于瘤周区域的小静脉，而不影响正常脑。然而，在血脑屏障破坏后的星形细胞瘤中以及任何患者的正常脑组织中均未观察到此类效应。看来，GM和脑转移瘤瘤周区域血脑屏障的完整性比星形细胞瘤或正常脑中的血脑屏障完整性更不稳定。渗透性血脑屏障破坏可能为实现治疗药物向脑肿瘤及瘤周区域的全面递送提供一种方法。
