Effect of hyperosmotic solutions on human brain tumour vasculature

Effect of hyperosmotic solutions on human brain tumour vasculature
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DOI:
10.1007/s007010050227
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发表时间:
1998-01-01
影响因子:
2.4
通讯作者:
Suga, S
Suga, S
中科院分区:
医学3区
文献类型:
--
作者:
Sato, S;Kawase, T;Suga, S

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血脑屏障(BBB)的可逆开放已被用于增加化疗药物向脑肿瘤的输送,但它很复杂,需要全身麻醉。在不影响正常血脑屏障的情况下,并避免了高渗溶液对血脑屏障修饰的并发症,我们在脑肿瘤中尝试了适当的最小血脑屏障破坏。尽管已经描述了BBB破坏对正常脑的影响,但是没有关于受损的BBB对微循环的影响的报道。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)或转移性脑肿瘤(n = 1)的手术切除。观察术野内的脑微循环。通过逆行输注甘露醇,将导管经颞浅动脉引回颈动脉分叉,在术中引入BBB破坏之前和之后,获得了肿瘤和瘤周区域的系列荧光素微血管造影照片。在最初的微血管造影中,在GM和转移性肿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。BBB中断后,荧光素灌注增加,并从微静脉中观察到的GM和转移性肿瘤和两个病变的瘤周区域的荧光素染料外渗; BBB中断开始从微静脉在瘤周区域,而不影响正常的大脑。然而,在BBB破坏后的星形细胞瘤和任何患者的正常脑组织中均未观察到这种作用。似乎在GM和转移性脑肿瘤的瘤周区域中,BBB的完整性不如星形细胞瘤或正常脑中稳定。渗透性血脑屏障破坏可能提供一种方法,实现全球交付的治疗剂的脑肿瘤和肿瘤周围地区。
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 rumours and peritumoural areas.