■ 8; 



HANDBOOK "1 I'HYSK H.< K;Y " NKl'Rt Jl'HYSlt >!.< >r;Y III 



DURA 



ARACHNOID 



SUBARACHNOID 

 SPACE 



BASEMENT 

 MEMBRANE 



OF 

 CAPILLARY 

 ENDOTHELIUM 



Fig. 4 Semidiagrammatic section of central iimiius s\ si cm and invest inn membranes, illustrating 

 relationships of \arious fluid compartments and barriers. Enlargement 'it towet left illustrates three 

 probable sites of blood-brain barrier action; capillary endothelium, basement membrane and peri- 

 vascular glia, Note that invaginating pia does not accompany penetrating vessels beyond larger 



branches. Astrocytes form an ()-, no' , tplete sheath around blood vessels, although only a few 



are illustrated Redrawn from Spatz (137).] 



ineffective when injected intravenousl) in doses io 

 times those which produced marked symptoms after 

 intrathecal administration. Biedl & Krans (16) in 

 1898 and Lewandowsk) 1 103) in 1900 showed similar 

 phenomena for bile and sodium ferricyanide, re- 

 specti\ eK . 



I lie classic experiments of this genre were con- 

 ducted li\ ( roldmann (55) from 1908 to 1913 using the 

 acid, semicolloidaJ <l\e trypan blue which has since 

 (nine to he regarded as the prototype of stains that, 

 in general, color the central nervous system onl) 

 aftei intrathecal injection 



In his 'Inst experiment,' Goldmann demonstrated 

 that, following intravenous injection, vital staining 

 occurred in all tissues of the organism except the 



brain which remained colorless with the notable ex- 

 ception of the choroid plexuses, I le observed no toxic 



symptoms in these animals, hut following inlralliei.il 



administration of the dye ('second experiment'), the 

 brain was stained deep blue, especially adjacent to 

 those subarachnoid areas into which the dye had 

 been introduced, and the animals developed seizures 

 and paralysis. He was led to the erroneous conclusion 

 that the seat of all blood-brain barrier activity was 



the choroid plexus, and lie expanded (his concept 



into the generalization that all substances must 

 pass from the Mood through the choroid plexus in 



order to enter the brain. The subsequent vicissitudes 

 ol that concept have been briefly described above. 



Walter ( 1 -,<)) in 1 ()-'<) concluded in a comprehensive 





