scholarly journals Effects of Epacadostat on Brain Extracellular Fluid Concentrations of Serotonin—an Intracerebral Microdialysis Study in Sprague-Dawley Rats

2019 ◽  
Vol 47 (7) ◽  
pp. 710-714
Author(s):  
Yan Zhang ◽  
Kevin Bowman ◽  
Janet Maleski ◽  
Sharon Diamond ◽  
Swamy Yeleswaram
2002 ◽  
Vol 22 (3) ◽  
pp. 271-279 ◽  
Author(s):  
Walid M. Abi-Saab ◽  
David G. Maggs ◽  
Tim Jones ◽  
Ralph Jacob ◽  
Vinod Srihari ◽  
...  

Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electro-physiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia–hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included. Under basal conditions, the authors found the metabolic milieu in the brain to be strikingly different from that in the circulation. In contrast to plasma, lactate levels in brain ECF were threefold higher than glucose. Results from complementary studies in rats were consistent with the human data. During the hyperglycemia–hypoglycemia clamp study the relationship between plasma and brain ECF levels of glucose remained similar, but changes in brain ECF glucose lagged approximately 30 minutes behind changes in plasma. The data demonstrate that the brain is exposed to substantially lower levels of glucose and higher levels of lactate than those in plasma; moreover, the brain appears to be a site of significant anaerobic glycolysis, raising the possibility that glucose-derived lactate is an important fuel for the brain.


1981 ◽  
Vol 240 (5) ◽  
pp. F395-F399
Author(s):  
A. U. Sheth ◽  
T. F. Knight ◽  
E. Pace ◽  
H. O. Senekjian ◽  
E. J. Weinman

Clearance and micropuncture studies were performed in Sprague-Dawley and Munich-Wistar rats to examine the nephron sites of chloride reabsorption in animals undergoing sustained volume expansion (SVE) (10% of body wt) with isotonic saline and in animals in which the extracellular fluid volume was expanded to 10% of body wt over 60 min, after which the sustaining saline volume was abruptly discontinued (recovery) (R). Net sodium and chloride balances were not significantly different in R compared with SVE. The fractional excretion of chloride, however, was significantly lower (2.62 +/- 0.25 vs. 4.18 +/- 0.62%, P less than 0.05). In the Sprague-Dawley rats, chloride delivery to the early distal tubule average 18% in both groups. Chloride delivery to the late distal tubule was significantly lower in R (4.39 +/- 0.79%) than in SVE (8.55 +/- 0.76%, P less than 0.005). In the Munich-Wistar rats, samples were obtained from the late distal tubule and base and tip of the papilla. Chloride delivery to the base did not differ from that to the late distal tubule in either group, but was significantly lower in R compared with SVE. These results indicate that the so-called “post-volume expansion” antinatriuresis is the result, at least in part, of enhanced reabsorption in the distal tubule.


1997 ◽  
Vol 273 (2) ◽  
pp. R587-R596 ◽  
Author(s):  
M. G. Tordoff

Polyethylene glycol (PEG) has been used to investigate the physiological basis of sodium intake because it sequesters sodium from the extracellular fluid (ECF) and causes rats to drink concentrated NaCl solutions. To test the hypothesis that PEG also depletes ECF calcium and thus activates calcium intake, male Sprague-Dawley rats received two-bottle tests with a choice between a taste solution and water. Relative to intakes after control injections, rats injected with PEG (5 ml of 30% wt/wt sc) drank significantly greater volumes of several calcium solutions (0.1, 1, 10, or 32 mM CaCl2 or 10 or 100 mM calcium lactate). They also drank more 10 mM SrCl2, 300 mM NaCl, and 100 mM KHCO3, drank less 10 mM sodium saccharin, and did not alter intakes of 10 or 100 mM KCl, 32 mM NH4Cl, 10 mM AlCl3, 10 mM FeCl2, 100 mM CaCl2, or 1,000 mM NaCl. Thus PEG treatment produced an appetite that was specific to low and moderate concentrations of calcium, sodium, and perhaps bicarbonate. The physiological basis for this appetite was explored. At 24 h after PEG injection, plasma total calcium concentrations were either unaltered or increased, but plasma ionized calcium concentrations were reduced. Concentrations of parathyroid hormone and calcitonin but not 1 alpha, 25-dihydroxyvitamin D3 were elevated. Perhaps one or more of these changes in calcium homeostasis is responsible for the increased calcium intake. Whatever the mechanism, it is clear that PEG treatment induces an appetite for calcium in addition to the well-known appetite for sodium.


2017 ◽  
Vol 14 (02/03) ◽  
pp. 122-128
Author(s):  
Yutaka Igarashi ◽  
Shoji Yokobori ◽  
Hidetaka Onda ◽  
Tomohiko Masuno ◽  
Hiroyuki Yokota

Abstract Object Many studies have reported that extracellular chemistry is related to the outcome of patients with traumatic brain injury (TBI). No study has reported that extracellular chemistry predicts outcome in less than 3 days. Moreover, in other studies, both focal brain and diffuse brain injuries have been often discussed. The authors focused on the relationship between extracellular chemistry in a shorter period and the outcome of patients with focal brain injury. Methods By using intracerebral microdialysis monitoring, extracellular fluid concentrations of glucose, lactate, glycerol, glutamate, lactate/pyruvate (L/P), and lactate/glucose (L/G) were determined in 30 patients with severe TBI for initial 24 hours. The results were analyzed between favorable and unfavorable, and between survival and mortality. Results The medians of glycerol and L/P in the favorable group were significantly lower than those in the unfavorable group (124 µmol/L vs. 808 µmol/L, p = 0.002; 31 vs. 48, p = 0.021, respectively). All parameters apart from glutamate differed significantly between the survival and mortality groups (glucose, 25 mmol/L vs. 77 mmol/L, p = 0.035; lactate, 38 mmol/L vs. 73 mmol/L, p = 0.018; glycerol, 168 µmol/L vs. 1462 µmol/L, p = 0.002; glutamate, 14 µmol/L vs. 95 µmol/L, p = 0.019; L/P, 32 vs. 124, p < 0.001; L/G, 1.46 vs. 4.52, p = 0.004). Conclusion Cerebral extracellular glycerol and L/P was the most reliable predictor of outcomes in patients with focal brain injury and can discriminate between favorable and unfavorable outcomes for the first 24 hours, using the threshold of 200 and 40, respectively.


1989 ◽  
Vol 257 (1) ◽  
pp. F23-F28 ◽  
Author(s):  
J. A. Joles ◽  
N. Willekes-Koolschijn ◽  
B. Braam ◽  
W. Kortlandt ◽  
H. A. Koomans ◽  
...  

Colloid osmotic pressure (COP) was measured in plasma and interstitial fluid (subcutaneous wick) from 8 to 75 days of age in Nagase analbuminemic rats (NAR) and control Sprague-Dawley rats (SDR). In all animals plasma COP (approximately 10 mmHg at 8 days of age) increased during growth. In the female NAR the rise in nonalbumin proteins was so large that at 75 days the plasma COP was not lower than in the SDR; whereas in male NAR a difference of approximately 4 mmHg remained. Interstitial COP increased with aging in the SDR, but not in the NAR. This resulted in equal transcapillary COP gradients in 75-day-old male and female SDR and male NAR (approximately 11–12 mmHg) but a somewhat larger gradient in the female NAR (approximately 14 mmHg). Blood pressure and plasma volume were not low in the NAR. Extracellular fluid volume (as a percentage of body weight) was similar in all groups and decreased with age. Clearances of 51Cr-labeled EDTA and 125I-labeled hippuric acid were decreased in young (45 day) NAR vs. young SDR, but not at 75 days of age. In conclusion, NAR are able to maintain a normal transcapillary COP gradient, and do not display signs of abnormal volume regulation during early development.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.


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