.8 7 4 



II VMlllOOK Hi- I'HYSIOI.OOY 



M I knl'HYSIOI.OCY III 



centra] nervous system was bound in organic com- 

 plexes within 2 min. after injection into the cerebro- 

 spinal fluid, as indicating a metabolic harrier oc- 

 curring in cell layers bordering the cerebrospinal 

 fluid system, lie believes that this barrier within the 

 cerebrospinal fluid-brain boundary delays the trans- 

 port of 1"'-' in such a way that the orthophosphate 

 rapidl) enters into organic compounds in the outer 

 cell layers and may subsequently enter the deep 

 structures of the brain by metabolic transportation 

 as well as diffusion. 



The ontogenetic maturation of the blood-brain 

 barrier has occupied considerable attention and has 

 recently been proposed as the explanation for the 

 development of kernicterus in babies with erythro- 

 blastosis (78). Irrespective of the blood level of bile 

 pigments in a jaundiced human adult, kernicterus 

 rarelv develops. On the other hand, Grontoft (60) 

 perfused human and animal fetuses with trypan blue 

 and found the brain normally impermeable to this 

 vital dye, even in human fetuses as early as the 5 cm 

 stage. Grazer & Clemente (57) similarly found that 

 the central nervous system of rat embryos from 10 

 days to birth is impermeable to trypan blue adminis- 

 tered in vivo. They conclude that this impermeability 

 in the developing central nervous system exists at the 

 time when blood vessels invade the brain. The) 

 caution, however, that it cannot be assumed that the 

 mechanisms which prevent protein-bound dyes from 

 penetrating the cerebral blood vessels are the same 

 for all other substances. Thus, with the application 

 of radiotracers, significant changes in rates ol penetra- 

 tion with age were observed, fries & Chaikoff (46, 47) 

 showed that the uptake of parenterally administered 

 l H - by liver, kidney, skeletal muscle and blood re- 

 mained constant or increased as the animal matured, 

 whereas uptake In the brain was greatly reduced. 

 Similarly, Bakav (<)) demonstrated that the perme- 

 ability of rabbit brain to P" is greatest in early uterine 

 life and continues to decrease until about 7 wk. of 



postn.it.il development. Despite tin- fact that the 

 embryonii and earl) postnatal brain concentrates 



considerably more P 82 than does the adult brain, its 

 uptake, as shown in figure ",, is still low w lien expressed 

 in absolute values and compared with any of the 

 other tissues (8). Baka) concludes thai even in the 

 Ictus there exists .1 barrier for P 8S between blood and 

 Centra] nervous svsiem, but the pernieabililv of this 

 b.u 1 lei is greater than in adults. 



Iii addition to certain of the investing membranes, 



there are several special Structures within the central 

 nervOUS svsiem ol adult animals which do become 



stained after parenteral injection of vital dyes or which 

 readily accumulate blood-borne radiotracers. These 

 include the pineal body, the pituitary gland, area 

 postrema, subfornical organ, supraoptic crest and 

 choroid plexuses. All of these regions are high]) 

 vascular, and many arc known, or suspected, to have 

 a secretory function. Borell & Orstrom (18) and 

 Bakav (9) have studied this relative absence of blood- 

 brain barrier activity with I" 2 (fig. 6) which ac- 

 cumulates in the hypophysis in a fashion similar to 

 its accumulation in the liver. Hcrlin (70) compared 

 the effects of intraperitoneal versus intracisternal ad- 

 ministration of P 3 - in rabbits and obtained results 

 completely in accordance with Goldmann's trypan 

 blue experiments. After intraperitoneal injection, 

 the tracer was concentrated in the choroid plexus but 

 almost absent from the neighboring wall of the ven- 

 tricle (fig. 4), whereas after intracisternal injection, 

 P 32 was concentrated in the ventricular wall while 

 the choroid plexus was almost free of radioactivity. 



The area postrema consists of a loose stroma con- 

 taining an abundance of sinusoidal vessels located in 

 the fourth ventricle between the mid-line and the 

 nucleus fasciculi gracilis. This structure has been ob- 

 served to stain with intravenous vital dyes (164) and 

 to accumulate P 8S (9) and Br* 2 (61 ). These unique 

 permeability characteristics have been proposed by 

 Andrew & Taylor (6) to account for their observation 

 that an area of special sensitivity to alterations of 

 tonicity in the cerebrospinal fluid exists in the floor of 

 the fourth ventricle, and by Clemente el al. (23) to 



INTRAUTERINE 



weens 



ik. -> I'- c urn 1 mi . n i< hi 111 various origans of fetal, young 



mil adult rabbits 9 1 I" after injection. [From Bakay (8). 





