Büttner Andreas, Kroehling Claus, Mall Gita, Penning Randolph, Weis Serge
Institute of Legal Medicine, Ludwig-Maximilians University, Frauenlobstrasse 7a, 80337 Munich, Germany.
Drug Alcohol Depend. 2005 Jul;79(1):63-70. doi: 10.1016/j.drugalcdep.2004.12.010. Epub 2005 Jan 26.
In drug abusers, white matter hyperintensities, perfusion deficits, and metabolic disturbances are detected by neuroimaging analyses in different brain regions. A specific pattern of involvement or a predominance of a specific brain region cannot be drawn. To examine changes of the cerebral microvasculature as a possible morphological substrate of the neuroimaging findings, brain specimens of 12 polydrug abusers and 8 controls were obtained at autopsy. The basal lamina of blood vessels from the frontal, temporal, parietal, and occipital lobes was analysed by means of immunohistochemistry for collagen type IV. The numerical density of vessels was determined in the gray and white matter, and their staining intensity was rated using a three-point scale. In the gray and white matter of polydrug abusers, the number of vessels showing strong immunoreactivity for collagen type IV was significantly reduced, whereas the number of vessels with mild and moderate immunoreactivity was increased as compared to controls. The total numerical density of vessels was not significantly changed. Our results show a significant reduction in immunoreactivity for collagen type IV in the brains from polydrug abusers compared to controls, which may be due to a thinning of the basal lamina of cerebral vessels. The data of the present study show morphological changes of the basal lamina in the brain of polydrug abusers, which might represent the morphological substrate of a disturbed blood-brain barrier. However, it remains yet to be established if the observed changes are responsible for the alterations seen in different neuroimaging analyses and which drug might be of major pathogenetic significance.
在药物滥用者中,通过神经影像学分析在不同脑区检测到白质高信号、灌注缺陷和代谢紊乱。无法得出特定的受累模式或特定脑区占优势的情况。为了检查脑微血管系统的变化作为神经影像学发现的可能形态学基础,在尸检时获取了12名多药滥用者和8名对照者的脑标本。通过免疫组织化学方法对额叶、颞叶、顶叶和枕叶血管的基底膜进行IV型胶原分析。测定灰质和白质中血管的数值密度,并使用三点量表对其染色强度进行评分。在多药滥用者的灰质和白质中,对IV型胶原显示强免疫反应性的血管数量显著减少,而与对照组相比,免疫反应性轻度和中度的血管数量增加。血管的总数值密度没有显著变化。我们的结果表明,与对照组相比,多药滥用者大脑中IV型胶原的免疫反应性显著降低,这可能是由于脑血管基底膜变薄所致。本研究的数据显示多药滥用者大脑基底膜的形态学变化,这可能代表血脑屏障紊乱的形态学基础。然而,观察到的变化是否是不同神经影像学分析中所见改变的原因以及哪种药物可能具有主要致病意义仍有待确定。