Experimental Study on the Genesis of Cerebral Vasospasm• The cerebral vasospasm produced by blood, fractions of blood, and blood-borne agents administered intracisternally was studied arteriographically to attain a better understanding of the genesis of vasospasm. The results indicate this phenomenon is multifarious in origin, involving a number of spasmogens. Whole blood, platelets, platelet extracts, some isolated components of platelets, plasma, thrombin, histamine, serotonin and prostaglandins Fi o , E2 and F 2a produced a significant incidence and duration of spasm. Norepinephrine and prostaglandin Ei were inactive. Spasm produced by arachidonic acid and red blood cells was of questionable significance.Compared to whole blood, thrombin usually produced spasm which was more delayed in onset while most other active substances produced a shorter-lived spasm. However, among the pure substances tested, serotonin, prostaglandin E2 and prostaglandin F 2o induced spasm in small doses which most nearly resembled that observed with whole blood.The hypothesis that the course of spasm depends upon synthesis of spasmogens by brain and blood is advanced. Prostaglandin synthesis plays a major role in this concept.

SUMMARYThe capacity of cerebral arteries to synthesize prostaglandins was studied by 2 procedures. In one, bovine cerebral arteries were incubated with 0.1 nC (lu C)-arachidonic acid for 3 hours. Using thin layer chromatography, 5 products of this arachidonic acid were isolated: prostaglandin E^ (PGE 2 ), prostaglandin F 2o (PGF 2o ), 6-keto prostaglandin F lo (6-keto PGF la ), prostaglandin D 2 (PGD 2 ), and thromboxane B 2 (TxB 2 ). In the second group of experiments the biosynthesis of these lipids from endogenous substrate was confirmed, except for PGD 2 , by means of gas liquid chromatography-mass spectroscopy. In addition, the production of PGE 2 and PGF 2a was quantified. An average of 196 ng PGF^ and 172 ng PGF 2a were synthesized per gram tissue in one hour. Meclofenamate inhibited the formation of these 2 prostaglandins while serotonin stimulated synthesis approximately 20-25%. The present finding demonstrates that cerebral arteries form several prostaglandins and, likely, thromboxane B 2 . It is hypothesized that these lipids may play a role in the vasomotion of cerebral blood vessels in health and disease. The relative rates of synthesis of these lipids may be important for maintaining normal cerebral circulation. However, in cerebrovascular disease the normal balance between the rate of synthesis of those prostaglandins which constrict and those which dilate may be disturbed.

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From the extracts of enzyme-or acid hydrolysed pregnancy urine and urine of newborn infants a new oestrogen metabolite has been isolated.On the basis of the physical and chemical characteristics of this compound it is concluded that it is identical with 15\g=a\-hydroxy-oestriol(oestra\x=req-\ 1 , 3 , 5 ( 1 0 ) -t r i e n e -3 , 1 5 \ g = a \ , 1 6 \ g = a \ , 1 7 \ g = b \ -t e t r o l ) .It has been reported from this laboratory that one of the quantitatively most important metabolites of radioactive 17/5-oestradiol injected to malformed infants is an oestrogenic tetrol. It has been suggested that this compound is identical with 15a-hydroxy-oestriol, or possibly with 18-hydroxy-oestriol (Hagcn et al. 1965). Continued studies revealed that this compound is a normal constituent of pregnancy urine, of the urine of newborn infants and meconium 1 Ford Foundation Fellow in Reproductive Endocrinology. Present address: