No abstract

We examined the metabolic disposition and brain distribution of an unsaturated fatty acid, [1-14C]arachidonate, between 5 and 240 min following its intravenous bolus injection in unanesthetized adult rats. Injected [1-14C]arachidonate was cleared rapidly from plasma, with less than 10% remaining by 2 min. Total brain radioactivity, 0.2% of the injected dose, was near maximal by 5 min, reached a peak by 15 min, then slowly declined. Radioactivity in brain lipids constituted greater than 82% of the total brain radioactivity at all times. Radioactivity in aqueous-soluble metabolites was greatest at 5 min (13% of total) and declined to 5% by 240 min. Protein pellet-associated radioactivity gradually rose to a peak of 7% by 120 min. Within the lipid fraction, more than 92% of radioactivity was in glycerolipids, with greater than 81% in phospholipids. Radioactivity in inositol phosphoglyceride was maximal at 5 min (47% of phospholipid radioactivity); and declined to 34% by 20 min, whereas radioactivity in choline phosphoglyceride peaked at 15 min (41% of phospholipid radioactivity) and was constant thereafter. In contrast, radioactivity in ethanolamine phosphoglycerides increased from 7 to 17% during the course of the experiment. Quantitative autoradiography of brain sections indicated incorporation of [1-14C]arachidonate into gray-matter regions was 1.5- to threefold that into white-matter regions. The data were analyzed in terms of a model for brain fatty acid uptake from plasma. Estimates of unidirectional transfer constants, k, for [1-14]arachidonate from plasma to brain regions with an intact blood-brain barrier ranged from 0.0005 to 0.0015 ml.sec-1.g-1 and were correlated with those for [9,10-3H]palmitate. The results indicate that brain phospholipid metabolism in awake animals can be examined regionally and quantitatively using intravenous injection of [1-14C]-arachidonate combined with quantitative autoradiography and biochemical analysis.

The distribution of radioactivity within brain metabolic compartments was examined following the intravenous injection of [9,10-3H]palmitate into awake rats. Brain radioactivity reached a maximum value by 15 min after [9,10-3H]palmitate injection and remained unchanged for at least 4 hr. Regional differences in radioactivity could be determined with high resolution by quantitative autoradiography, at the level of cell layers within the hippocampus and cerebral cortex, and between striosomes of the caudate nucleus. Regional brain radioactivities were converted to normalized regional radioactivities (k) by dividing them by the integrated plasma fatty acid radioactivity (integrated over the time course of the experiment). These values reflected incorporation mainly into brain phospholipids; radioactivity due to nonlipid components was minimal. Indeed, about 85% of brain radioactivity was within lipids between 5 min and 4 hr postinjection, the remainder being equally divided between protein-associated pellet and aqueous-soluble metabolites. The major lipids labeled were phospholipids, particularly phosphatidylcholine, which contained about 75% of phospholipid radioactivity. The results show that [9,10-3H]palmitate can be used to examine incorporation of plasma palmitate into individual brain regions via quantitative autoradiography. Furthermore, the tracer is a rather selective marker for phosphatidylcholine and can be used to examine turnover and synthesis of this phospholipid. [9,10-3H]palmitate has advantages over [U-14C]palmitate for autoradiographic studies of incorporation; following the 14C-tracer, significant label even at 4 hr after injection is in nonlipid compartments (glutamate and aspartate), and the long path length of 14C limits resolution at the cell layer level.

Positron emitting dl-erythro-9,10[18F]difluoropalmitate, [18F]DFPA, was synthesized for the in vivo imaging of brain tumors in rats. Male Fischer 344 rats were intracerebrally implanted with Walker 256 carcinosarcoma tumor cells (1 x 10(6) in 5 microliters tissue culture media) and 7 days later were infused with [18F]DFPA (500-1000 mCi/mmol) i.v. for 5 min. Rats were killed after 20 min. Brains were removed and either prepared for autoradiography, or brain and tumor were separated and their radioactivity quantified by gamma spectroscopy. Brain tumors were well demarcated from surrounding and normal brain in autoradiographs, and closely paralleled tumor growth in histological sections. The mean optical density of tumor was significantly greater, by 318 +/- 68 per cent (P less than 0.025, n = 3), than normal brain in autoradiographs, and that of edematous brain surrounding a large tumor was intermediately increased. [18F]DFPA proved of value to image and circumscribe intracerebral tumors in awake rats, and studies are continuing to facilitate its clinical application in brain tumor patients.

No abstract

No abstract

Male Wistar rats were castrated on the day of birth and divided into two groups; the first was injected with 0\m=.\1mg. testosterone propionate (TP), on the day of castration and the second with 0\m=.\5 mg. TP after day 10. When 45 days old, all were grafted with an ovary in the kidney. Animals in the first group showed ovaries with ripening follicles without corpora lutea; those in the second group had corpora lutea at different stages of maturation. Ovaries grafted into female rats spayed on the day of birth developed luteinization even when injected with 0\m=.\5mg. TP after the 10th day of life, but not if the hormone was injected earlier.Since the hypothalamus is sensitive to androgens only before the 10th day of life even in gonadectomized rats, it can be argued that the female pattern of gonadotrophin control does not correspond to the undifferentiated hypothalamus but depends on some active central mechanism. The period during which the hypothalamus is still sensitive to androgens would correspond to the undifferentiated equipotential stage.

No abstract