Bigotte L, Olsson Y
Acta Neurol Scand Suppl. 1984;100:55-67.
Adriamycin (doxorubicin) is commonly used in the treatment of malignant tumours. Adverse effects on the CNS have not been described so far, but the patients may suffer from a dose-related myocardial toxicity. Lesions have previously been observed in peripheral ganglia of experimental animals. Using a direct fluorescence microscopic method we have investigated the distribution of adriamycin in the CNS of normal mice after various modes of administration. Adriamycin, after intravenous (i.v.) injection, did not pass into the brain generally but entered the choroid plexus and circumventricular organs, namely the median eminence, postremal area, subfornical organ, organum vasculosum of the lamina terminalis, pineal gland, and neurophypophysis. After a single i.v. injection of the drug, the animals showed distinct morphological changes in three regions examined thus far, the neurohypophysis (NH), median eminence (ME), and postremal area (PA). In the NH and ME many degenerated neurosecretory axon terminals were observed. In addition, nuclear and cytoplasmic changes were seen in the pituicytes and glial cells of the ME. The PA showed severe neuronal alterations which included nucleolar segregation, rarefaction of the nuclear chromatin, and cytoplasmic changes. When the blood-brain barrier was circumvented by direct microinjection into the cerebral ventricles, the drug passed into the surrounding brain parenchyma, being detected in the nuclei of both neurons and glia. It can therefore be assumed that, when adriamycin is given to patients with a disturbance of the blood-brain barrier, the drug may spread into the brain in the same way. The blood-brain barrier can also be bypassed by injecting a substance intramuscularly or/and intradermally and letting it pass into the spinal cord or brain-stem by retrograde axonal transport. In model experiments, adriamycin was injected into the tongue and six hours later its fluorescence could be detected in the hypoglossal neurons. Animals allowed to survive for a longer period, showed selective damage to these neurons as evidenced by early nuclear changes followed by alterations in the cytoplasm.(ABSTRACT TRUNCATED AT 400 WORDS)
阿霉素（多柔比星）常用于治疗恶性肿瘤。目前尚未发现其对中枢神经系统有不良反应，但患者可能会出现与剂量相关的心肌毒性。此前在实验动物的外周神经节中观察到了病变。我们使用直接荧光显微镜法研究了正常小鼠在不同给药方式后阿霉素在中枢神经系统中的分布情况。静脉注射阿霉素后，一般不会进入脑内，但会进入脉络丛和室周器官，即正中隆起、最后区、穹窿下器官、终板血管器、松果体和神经垂体。单次静脉注射该药物后，在目前检查过的三个区域，即神经垂体（NH）正中隆起（ME）和最后区（PA）出现了明显的形态学变化。在神经垂体和正中隆起中，观察到许多退化的神经分泌轴突终末。此外，正中隆起的垂体细胞和神经胶质细胞出现了核及细胞质变化。最后区出现了严重的神经元改变，包括核仁分离、核染色质稀疏和细胞质变化。当通过直接向脑室微量注射绕过血脑屏障时，药物进入周围脑实质，并在神经元和神经胶质细胞的细胞核中被检测到。因此可以推测，当给血脑屏障有障碍的患者使用阿霉素时，药物可能会以同样的方式扩散到脑内。通过肌肉内或/和皮内注射一种物质，让其通过逆行轴突运输进入脊髓或脑干，也可以绕过血脑屏障。在模型实验中阿霉素被注射到舌部，6小时后在舌下神经元中可检测到其荧光。存活较长时间的动物，这些神经元出现了选择性损伤，早期核变化后接着细胞质改变就是证据。（摘要截于400字）
