Disruption of the blood-brain barrier following ALA-mediated photodynamic therapy.
Disruption of the blood-brain barrier following ALA-mediated photodynamic therapy.
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DOI：
10.1002/lsm.20670
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发表时间：
2008-10
影响因子：
2.4
通讯作者：
Madsen, Steen J.
中科院分区：
文献类型：
--
作者：
Hirschberg, Henry;Uzal, Francisco A.;Chighvinadze, David;Zhang, Michelle J.;Peng, Qian;Madsen, Steen J.
光动力疗法（PDT）是一种具有肿瘤细胞特异性的局部治疗方法。已报道使用血卟啉衍生物或5-氨基乙酰丙酸（ALA）的PDT诱导脑水肿，表明血脑屏障（BBB）的破坏。我们已经评估了ALA介导的PDT打开大鼠血脑屏障的能力。这将允许化疗剂接近残留在切除腔壁中的脑肿瘤细胞，但限制它们渗透到远离照射部位的正常脑中。ALA-PDT在非荷瘤近交系Fischer大鼠上以增加的能量密度水平进行。对比T1加权高场（3 T）磁共振成像（MRI）扫描用于监测BBB破坏的程度，这可以从可视化的造影剂的强度和体积推断。PDT在9和26 J之间的增加的能量密度水平表现出增加的对比剂流速。随着注量率的增加，观察到类似的造影剂体积增加。在PDT后2小时发现血脑屏障被破坏，72小时后在最低能量密度水平下恢复80-100%。如果在不存在ALA的情况下给予26 J的光，则未观察到对BBB的影响。ALA-PDT在打开脑局部区域的BBB方面非常有效。在9 J的注量水平下，BBB的降解本质上是暂时的，在治疗后迅速开放，并在接下来的72小时内显著恢复。在该能量密度水平下，在组织切片上未观察到组织损伤迹象。然而，更高的能量密度确实证明了位于光源附近的永久性组织变化。
Photodynamic therapy (PDT) is a local antineoplastic treatment with the potential for tumor cell specificity. PDT using either hematoporphyrin derivatives or 5-aminolevulinic acid (ALA) has been reported to induce brain edema indicating disruption of the blood–brain barrier (BBB). We have evaluated the ability of ALA-mediated PDT to open the BBB in rats. This will permit access of chemotherapeutic agents to brain tumor cells remaining in the resection cavity wall, but limit their penetration into normal brain remote from the site of illumination. ALA-PDT was performed on non-tumor bearing inbred Fischer rats at increasing fluence levels. Contrast T1-weighted high field (3 T) magnetic resonance imaging (MRI) scans were used to monitor the degree of BBB disruption which could be inferred from the intensity and volume of the contrast agent visualized. PDT at increasing fluence levels between 9 and 26 J demonstrated an increasing contrast flow rate. A similar increased contrast volume was observed with increasing fluence rates. The BBB was found to be disrupted 2 hours following PDT and 80–100% restored 72 hours later at the lowest fluence level. No effect on the BBB was observed if 26 J of light was given in the absence of ALA. ALA-PDT was highly effective in opening the BBB in a localized region of the brain. The degradation of the BBB was temporary in nature at fluence levels of 9 J, opening rapidly following treatment and significantly restored during the next 72 hours. No signs of tissue damage were seen on histological sections at this fluence level. However, higher fluences did demonstrate permanent tissue changes localized in the immediate vicinity of the light source.
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影响因子：
4.1
作者：
LIEBERMAN, DM;LASKE, DW;OLDFIELD, EH
通讯作者：
OLDFIELD, EH
影响因子：
4.1
作者：
Angell-Petersen, E;Spetalen, S;Hirschberg, H
通讯作者：
Hirschberg, H
DOI：
10.1073/pnas.91.6.2076
发表时间：
1994-03-15
影响因子：
11.1
作者：
BOBO, RH;LASKE, DW;OLDFIELD, EH
通讯作者：
OLDFIELD, EH
影响因子：
--
作者：
CHENG, MK;MCKEAN, J;TULIP, J
通讯作者：
TULIP, J
影响因子：
2.4
作者：
Hebeda, KM;Saarnak, AE;Wolbers, JG
通讯作者：
Wolbers, JG