Mapping ALA-induced PPIX fluorescence in normal brain and brain tumour using confocal fluorescence microscopy.
Mapping ALA-induced PPIX fluorescence in normal brain and brain tumour using confocal fluorescence microscopy.
复制标题
使用共焦荧光显微镜绘制正常脑和脑肿瘤中 ALA 诱导的 PPIX 荧光图。
DOI：
10.3892/ijo.25.1.37
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发表时间：
2004
影响因子：
5.2
通讯作者：
B. Wilson
中科院分区：
文献类型：
--
作者：
M. Olivo;B. Wilson
我们绘制了静脉注射ALA后不同时间间隔氨基乙酰丙酸（ALA）诱导的原卟啉IX （PPIX）在正常兔脑组织和脑肿瘤组织中的微观分布。在正常大脑中，没有血脑屏障（BBB）的区域，如脉络膜丛和脑膜，以及与脑脊液相关的结构，合成PPIX的量最高。血清ALA浓度高时，我们也在给药后2小时内检测到脑脊液中的ALA。我们的荧光研究表明，ALA能够穿过完整的血脑屏障，并在血脑屏障区域代谢。在远离脑膜或脉络膜丛的大脑区域，如海马体、丘脑、小脑叶和脑干，这一点很明显。然而，这些区域的相对PPIX荧光峰值远低于没有血脑屏障的区域。我们的影像学研究表明，正常脑血脑屏障完好的不同区域的神经元代谢ALA的能力不同。大脑和小脑的灰质区域也比相同结构的白质区域显示出更高的PPIX荧光。我们的研究表明，与正常对侧大脑皮层相比，肿瘤组织具有最高的PPIX荧光。肿瘤和正常组织在24小时之间达到了最大的选择性。正常血管中的PPIX荧光似乎主要是由于血清中内化ALA的代谢，而不是由于PPIX水平高。总之，ALA确实穿过血脑屏障和除下丘脑外的所有大脑区域，表现出ALA动态合成PPIX。与正常脑组织相比，肿瘤和炎症脑组织中PPIX积累增加，表明这种组织选择性光敏化的可行性。
We have mapped the microscopic distribution of aminolevulinic acid (ALA) induced protoporphyrin IX (PPIX) in normal rabbit brain and in brain tumour at various time intervals after i.v. injection of ALA. In normal brain, regions without a blood-brain barrier (BBB) such as the choroid plexus and meninges and also structures associated with the CSF synthesized the highest amounts of PPIX. We also detected ALA in the CSF within 2 h after ALA administration when the serum concentration was high. Our fluorescence studies have shown that ALA is able to cross an intact BBB and be metabolized in regions with a BBB. This is evident in regions of the brain such as the hippocampus, thalamus, cerebellar folia and brain stem that are remote from the meninges or choroid plexus. However, the relative peak PPIX fluorescence in these regions are much lower than in regions without a BBB. Our imaging studies have shown that neurons in different regions of normal brain with an intact BBB exhibit varying capacities to metabolize ALA. The grey matter regions of the cerebrum and cerebellum also showed higher PPIX fluorescence compared to white matter regions in these same structures. Our study showed that tumour tissue had the highest PPIX fluorescence compared to normal contralateral cerebral cortex. Maximum selectivity was achieved between tumour and normal tissue at 24 h. PPIX fluorescence in normal blood vessels appear to be mainly due to metabolism of internalized ALA from serum and not due to high PPIX levels. In conclusion, ALA does cross the BBB and all regions of the brain with the exception of the hypothalamus, exhibit a dynamic synthesis of PPIX from ALA. Increased PPIX accumulation in tumour and inflamed brain tissue in comparison to normal brain tissue suggest the feasibility of selective photosensitization of such tissue.