Ethylnitrosourea誘発ラット脳腫瘍における血脳関門の変化

CHANGES OF BLOOD-BRAIN BARRIER IN THE ETHYLNITROSOUREA INDUCED RAT GLIOMA

I．はじめに

　悪性脳腫瘍の増殖に伴う腫瘍および腫瘍周辺脳組織の血脳関門の変化を解明することは，腫瘍の病態を知る上で重要である。また悪性脳腫瘍の化学療法においても，親水性制癌剤の腫瘍内へのとりこみは血脳関門の変化に比例すると考えられており^5,6），血脳関門の腫瘍内局所での変化を知ることが重要となつている。しかしながら，ヒト脳腫瘍で血脳関門の変化を定量的に検索することは現在のところ困難である。そこで私達はヒト神経膠腫と類似した所見を量するethylnitrosourea （ENU）誘発ラット神経膠腫^4）を用いて，局所毛細血管透過性をauto—radiography法により定量し，腫瘍内および周辺脳組織内の血脳関門の変化を検討した。

Capillary permeability of rat brains bearing ethylnitrosourea induced rat glioma was measured with quantitative autoradiography.

In the small tumors (<2mm in diameter), no changes in capillary permeability was noted. When tumors became larger and neovascularization of the tumor occurred, increase in capillary perme-ability was evident. This change was more pro-minent in the center of the tumor than in the periphery. In the large tumors, the capillary permeability was markedly increased, and the value was similar to that in the choroid plexus. This indicates that blood-brain barrier (BBB) completely disappeared in the large tumors.

This BBB change may be the main cause of tumor induced brain edema. The data also provide the information about pharmacokinetics of water soluble drugs in the brain tumors.