Brain Research, 548 (1991) 267-272 © 1991 Elsevier Science Publishers B.V. 0006-8993/91/$03.50 A DONIS 000689939116584G

267

BRES 16584

Species differences in cerebral taurine concentrations correlate with brain water content Malgorzata Puka 1'*, Kristina Sundell 2, Jerzy W. Lazarewicz 3 and Anders Lehmann 1 Ilnstitute of Neurobiology and 2Department of Zoophysiology, University of Grteborg, Grteborg (Sweden) and 3Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warsaw (Poland) (Accepted 4 December 1990)

Key words: Amino acid; Cerebral edema; Volume regulation; Osmolality

The notion that taurine (Tau) has an osmoregulatory function in the mammalian brain has not been established, although it has been reported that the severity of hyponatremic edema is proportional to cerebral [Tau]. Tau pools are not easily altered in vivo, but the fact that there are large differences in cerebral taurine levels between mice, rats and guinea pigs offers an opportunity to determine whether endogenous Tau affects volume regulation of the brain in hyposmolal conditions. This issue was investigated by injecting saline or distilled water intraperitoneally at 150 ml/kg in anesthetized mice, rats and guinea pigs. The animals were decapitated 4 h later, and blood osmolality, cortical specific gravity, Na +, K+ and amino acid concentrations were determined. In controls, blood osmolality and specific gravity of the cortex were highest in the mouse (304 + 3 mmol/kg; 1.0488 + 0.0003 kg/l), followed by the rat (294 + 1; 1.0462 + 0.0002) and the guinea pig (285 + 2; 1.0445 + 0.0002). There was a correlation between these measures and cortical Tau levels which were 10.31 + 0.36 mmol/kg in mouse cortex, 6.31 + 0.18 in rat cortex and 1.37 + 0.06 in guinea pig cortex. Despite these differences, water-induced cerebrocortical swelling did not differ between the species studied. Interspecies variation in cortical osmolality did not relate to [Na÷] and [K+], since the levels of these electrolytes were higher in the guinea pig cortex than in the rat and mouse cortex. After administration of water, the levels of Na ÷ and K ÷ were reduced in rat and guinea pig cortex, while only [Na÷] was significantly decreased in mouse cortex. The absence of any differences in swelling of mouse and rat cortex, in spite of a two-fold greater reduction in [Na+] and [K÷] in the latter, indicates that the mouse is more dependent on organic osmolytes in volume regulation during acute hyposmolality. This suggestion is supported by the finding that there was a net decrease in amino acids in the mouse cortex, but not in the rat cortex. While the results do not provide any evidence for a role of Tau in acute brain edema, they show, for the first time, a close association between brain water and Tau content.

INTRODUCTION

Astrocytes in primary culture release large a m o u n t s of Tau in the course of iso- or hyposmotic swelling9'14A9'2°,

A m o n g the amino acids that are recognized as m a j o r organic osmolytes in various marine animals, taurine (Tau) is quantitatively the most important 3-5. Although present at much lower concentrations, Tau has been proposed to serve a similar role in the m a m m a l i a n brain. Cerebral pools of this amino acid increase in chronic hyperosmotic disturbances22 and decrease in response to chronic hyposmotic conditions 1°'23. Recent observations have d e m o n s t r a t e d that t r a n s m e m b r a n e fluxes of Tau in CNS preparations are controlled by cellular volume. In brain microdialysis experiments, perfusion with hyposmotic buffers 12'21'27, or with isosmotic, hypotonic

and spontaneous release is suppressed 14 when they are exposed to hyperosmotic buffers. Although it has now b e e n established that the release of Tau is generally osmosensitive, few studies have addressed whether Tau acts as an osmoregulator. Evidence in support of such a function comes from the work

buffers 2, stimulates Tau release, whilst hyperosmotic buffers 12 produce the opposite effect. The concentration of Tau increases in cerebral microdialysates and CSF during systemic water intoxication11'27, partly as a consequence of a p r o n o u n c e d elevation of plasma Tau xl.

of Trachtman and associates who reported that the Tau-deficient kitten loses more brain water in chronic hypernatremia than T a u - s u p p l e m e n t e d controls 24. Moreover, Tau deficiency protects against hyponatremiainduced cerebral e d e m a 25, an i m p o r t a n t finding that requires further investigation. In the present study, the hypothesis that high concentrations of taurine in the brain accentuates hyposmotic cerebral swelling was tested by comparing the effects of acute water intoxication in mice, rats and guinea pigs. Bearing in mind the observations of Trachtman et al. 25, it was postulated that

* On leave of absence from the Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

Correspondence: A. Lehmann, Institute of Neurobiology, University of GOteborg, P.O. Box 33031, S-400 33 GOteborg, Sweden.

268 the mouse brain would be most prone to swelling since it contains high levels of Tau (10-12 mmol/kg wet weight), and that the guinea pig brain (1-2 mmol/kg w.w.) would be more resistant to swelling. The rat brain (5-7 mmol/kg w.w.) would be expected to fall in between these

detection ~3. Ea eluted between tt-aminobutyric acid and cystathionine with a retention time of 41.2 rain. The signals from the detector were acquired and integrated with a PC using Waters 800 Maxima Program. In order to eliminate the effect of passive dilution on amino acid levels in the brain of water-intoxicated animals, individual amino acid data were divided by 100% + % individual volume increase,

extremes. This interspecies comparison can only be justified if relative decreases in blood osmolality and m a j o r cerebral inorganic osmolytes (Na ÷ and K ÷) are known. These variables were consequently also quantitated, as well as brain amino acid content.

MATERIALS AND METHODS Male Sprague-Dawley rats (Alab, Sollentuna, Sweden; mean weight 345 _+ 5 g), NMRI mice (Alab; 37.4 _+ 0.5 g) and Dunkin-Harley guinea pigs (Salins marsvinsfarm, Maim0, Sweden; 515 _+ 22 g) were anesthetized with an intraperitoneal injection of urethane (1.25 g/kg). Isotonic NaCI (measured osmolality approximately 290 mmol/kg; 37 °C) or distilled water (37 °C) was administered intraperitoneally at a dose of 150 ml/kg. The animals were killed by decapitation 4 h later. Blood was collected in heparinized Eppendorf test tubes for measurement of osmolality. The brain was rapidly isolated and the hemispheres were separated. One was immediately frozen in liquid nitrogen and stored at -80 °C for determination of amino acids, Na + and K+. The other hemisphere was placed in cold kerosene. The parietal cortex was dissected into small cubes for measurement of specific gravity.

Blood osmolality Osmolality of heparinized blood was measured immediately after sampling with a Wescor 5000 vapor pressure osmometer. Blood osmolality was determined in duplicate or triplicate 10-/zl samples. Cortical specific gravity Specific gravity, rather than wet weight/dry weight, was used as an estimate of water content. Although specific gravity is an indirect measure of tissue water, it correlates exactly with results obtained with the weighing method s . The specific gravity method is considerably more sensitive than the weighing method. A bromobenzenekerosene specific gravity gradient TM was prepared in a graded 500 ml cylinder using a gradient mixer. The gradient was standardized with K2SO 4 solutions with varying specific gravity. Duplicate cortical samples were placed in the gradient, and their specific gravity was determined graphically from standard curves. The position of standards and biopsies was read 5 min after immersion, and standardization was repeated regularly to compensate for the small changes in the gradient that occasionally occurred during an experiment. Relative volume changes were calculated according to the method of Nelson et al.16: %

increase

=

[(specific gravityi - 1)/(specific gravityh -

1) -

Cortical content of Na and K Cortical biopsies were dried at 90 °C to constant weight. The tissue was digested in 65% HNO 3 (1 ml/100 mg d.w.) for a minimum of 48 h. The extracts were analyzed for Na ÷ and K+ concentrations by flame emission spectroscopy (Turner 510) using lithium as internal standard. Statistics The results are reported as means + S.E.M. Student's two-tailed t-test for unpaired observations was used to analyze differences between saline- and water-injected animals. The relationship between cortical amino acid content and specific gravity was analyzed using simple regression. Although it may not be statistically correct to apply regression analysis on clustered data such as that obtained, the method was used for illustrative purposes.

RESULTS Administration of 150 mt/kg saline was not associated with any mortality in rats (n = 6), guinea pigs (n = 5) or mice (n = 6). Whereas all water-injected rats (n = 6) survived the experimental period, one out of 7 guinea pigs died 75 min after administration of water. The mouse was considerably more sensitive to acute plasma hyposmolality: the dose used approximated the LDs0 for mice, since 6 out of 13 mice died (mean time of death: 45 + 3 min). The reason for this high sensitivity was not clear, but it was noted that water-intoxicated mice hypoventilated. In contrast, rats hyperventilated, whilst the ventilation rate of guinea pigs appeared unaffected.

Blood osmolality The blood osmolality of saline-injected mice was higher than that of rats, which in turn was higher than that of guinea pigs (Table I). A d m i n i s t r a t i o n of water reduced the osmolality by 18.0% in guinea pigs, by 16.8% in mice and by 15.0% in rats (Table I).

1] ×

100 where subscripts i and h denote isosmotic and hyposmotic groups, respectively.

Cortical amino acids and ethanolamine (Ea) Parietal cortex from the frozen hemisphere was dissected, weighed and homogenized in 10 vols. 0.6 M perchloric acid. The homogenate was centrifuged (20 min, 20,000 g) and the supernatant was neutralized with 2 M KHCO 3 (60 /~1 supernatant + 45 /A KHCO3). The resulting precipitate was removed by centrifugation (20 min, 20,000 g). The amino acid and Ea concentration of the extract was determined with automatic precolumn derivatization with o-phthalaldehyde, reversed-phase separation of derivatives and fluorimetric

Specific gravity o f the cortex Interspecies differences in cortical specific gravity were observed (Table I), and they corresponded closely to blood osmolalities. The mouse showed the highest value, the rat an intermediary value and the guinea pig the lowest value. Water-induced swelling was most pron o u n c e d in the guinea pig (12.4%), followed by the mouse (9.8%) and the rat (8i6%). These differences did not relate to true species dissimilarities but rather to disparities in the water-induced reduction of blood osmolality (Table I).

269 TABLE I

12'

Plasma osmolality and specific gravity of the cerebral cortex of saline or water-injected mice, rats and guinea pigs Blood osmolality was measured with vapor pressure osmometry, and specific gravity with bromobenzene/kerosene gradients. Blood osmolality and cortical specific gravity were significantly (P < 0.001) reduced in animals given water compared with saline-injected controls.

Species Mouse Saline Water Rat Saline Water Guinea pig Saline Water

Plasma osmolality (mmol/kg)

Specific gravity (kg/l)

304 + 3 253 + 2

1.0488 + 0.0003 1.0445 + 0.0002

294 + 1 250 _ 2

1.0462 + 0.0002 1.0425 + 0.0003

285 + 2 234 + 2

1.0445 + 0.0002 1.0396 + 0:0002

o~o o

10'

o

o

o

Mouse

8'

o

o

4'

2'

.



1,0441,~k51.{)461,047 1,~t8 1,0491,050 Cortical specific gravity (kg/1) Fig. 1. Simple regression analysis of cortical specific gravity and Tau concentrations in saline-injected animals; R E = 0.872, P < 0.0001.

A m i n o acids and Ea The (Glu),

concentrations glutamine

of aspartate

(Gin),

(Asp),

glutamate

phosphoethanolamine

A s p , G l u and P e a w e r e significantly r e d u c e d , a n d E a was

(Pea),

m a r k e d l y e l e v a t e d , in all species. Tau was significantly

E a , T a u , a l a n i n e ( A l a ) a n d 7 - a m i n o b u t y r a t e ( G A B A ) in

d e c r e a s e d in g u i n e a pigs and m i c e , but n o t in rats. T h e

rat, m o u s e a n d g u i n e a pig c o r t e x are s h o w n in T a b l e II.

rest o f t h e a m i n o acids t e n d e d to c h a n g e in the s a m e

T h e t o t a l levels o f t h e s e a m i n o acids and E a w e r e highest

d i r e c t i o n in t h e d i f f e r e n t species. T h e n e t d e c r e a s e in

in t h e m o u s e (38.1 m m o l / k g w . w . ) , f o l l o w e d by the rat

total a m i n o acids was 6.15 m m o i / k g w . w . for m i c e , 3.24

(33.0 m m o l / k g w . w . ) a n d t h e g u i n e a pig (23.4 m m o l / k g

for g u i n e a pigs a n d 1.11 for rats.

w . w . ) . C o n s i d e r a b l y h i g h e r levels o f Tau and G i n in the

T h e r e was a s t r o n g r e l a t i o n (R 2 = 0.872; P -- 0.0001)

m o u s e c o r t e x a c c o u n t e d m a i n l y for t h e d i f f e r e n c e c o m -

b e t w e e n t h e i n t e r s p e c i e s disparities in c o r t i c a l specific

p a r e d with rats, w h i l e t h e m a i n r e a s o n for the h i g h e r total

gravity a n d [Tau] (Fig. 1). W i t h t h e e x c e p t i o n o f G i n (R 2

a m i n o acid c o n c e n t r a t i o n in rats c o m p a r e d with g u i n e a

-- 0.546; P -- 0.0007), n o o t h e r a m i n o acid o r E a s h o w e d

pigs w e r e d i f f e r e n c e s in Tau and G l u .

a similar c o r r e l a t i o n with cortical specific gravity. Intra-

T h e effects o f a c u t e p l a s m a h y p o s m o l a l i t y o n a m i n o

species r e g r e s s i o n analysis o f c o r t i c a l Tau levels and

acids w e r e , in q u a l i t a t i v e t e r m s , a l m o s t identical in the

specific gravities did n o t r e v e a l a n y r e l a t i o n s h i p b e t w e e n

d i f f e r e n t species ( T a b l e II). T h u s , t h e c o n c e n t r a t i o n s of

t h e s e p a r a m e t e r s (Fig. 2).

TABLE II

Amino acid concentrations (mmol/kg wet weight) in the cerebral cortex of mice, rats and guinea pigs injected with saline or water Amino acids were analyzed with precolumn derivatization with o-phthalaldehyde, reversed-phase HPLC separation and fluorescence detection. Correction was made for the increased cortical volume of water-injected animals, ap < 0.05; bp < 0.01; cp < 0.001 (Student's unpaired t-test, two-tailed).

Amino acid

Mouse

Asp Glu Gin Pea Tau Ala GABA Ea

2.19 9.48 9.99 2.97 10.31 0.28 2.78 0.12

Saline + 0.13 _+0.57 + 0.76 + 0.11 _+0.36 + 0.01 + 0.16 + 0.01

Rat

Guinea pig

Water

% change

Saline

Water

% change

Saline

0.86 + 0.05 c 6.18 + 0.35 c 11.42 _+ 0.72 2.14 _+ 0.13 c 8.62 + 0.47 a 0.28 _+0.03 2.14 _+ 0.36 0.33 _+ 0.02c

-60 -35 + 14 -28 -16 +0 -23 +175

3.03 + 0.20 11.21 + 0.19 6.93 + 0.12 2.47 _+0.06 6.31 _+ 0.18 0.33 + 0.01 2.52 + 0.16 0.19 _+ 0.01

1.90 + 0.07 c 8.44 + 0.30¢ 10.95 + 0.48¢ 1.92 _+ 0.08 c 6.02 + 0.16 0.30 + 0.01 1.87 + 0.13 b 0.48 + 0.02 c

-37 -25 +58 -22 -4 -9 -26 +153

2.30 7.69 6.44 3.01 1.37 0.25 2.25 0.10

+ + + + + + + +

Water 0.11 0.11 0.32 0.17 0.06 0.01 0.38 0.01

1.26 6.02 7.58 1.91 1.07 0.22 1.49 0.62

+ + + + + + + +

% change 0.11 c 0.41 b 0.50 0.12 ¢ 0.08 a 0.02 0.10 0.05 ¢

-45 -22 + 18 -36 -22 -12 -34 +520

270 Na and K

The content of Na + and K + in dried cortical samples from saline-injected animals (Table III) exhibited the ll

Mouse

10

reverse pattern as compared with total amino acid levels: i.e. the levels of both Na + and K + in guinea pig cortex were higher than in rat cortex which, in turn, were slightly higher than in mouse cortex. Acute plasma hyposmolality produced significant decreases in [Na +] and [K +] in rat and guinea pig cortex (Table III). The concentration of Na + was significantly depressed in mouse cortex, but the K + concentration was unaffected. The relative as well as absolute reduction in these electrolytes was greatest in rats, followed by guinea pigs and mice (Table II1). DISCUSSION

1.~15

1.043

Specific gravity (kg/1) 6.8

¸

Rat

6.6 6.4 6,2 v

6,0' 5,8' 5.6 1.041

1.642

1.643

1.6

Specific gravity (kg/1) Guinea-pig

1,2 1,1 1,0 v

0.9 0,8 0.7 1.038

1.039

1,640

1.041

Specific gravity (kg/1) Fig. 2. Regression analysis of intraspecies data on cortical specific gravity and Tau levels in water-injected animals. R 2 (mouse) = 0.001 (n.s.); R E (rat) -- 0.027 (n.s.) and R 2 (guinea pig) = 0.164

(n.s.).

The main purpose of the present work was to assess whether there is a relationship between the brain's propensity to swell in hyposmolal conditions and its Tau concentrations. This has shown to be the case in kittens supplemented with or deprived of dietary Tau; a decrease in brain Tau amounting to as little as 1.5 mmol/kg offers a significant protection against hyponatremic edema 25. Since the differences in cerebral taurine between mice, rats and guinea pigs are considerably greater than 1.5 mmol/kg, water intoxication was expected to produce a distinctly graded cerebral edema in the species investigated. However, this proved not to be the case. The differences in water-induced cortical swelling corresponded to differences in blood osmolality reductions: the more marked cerebral edema in guinea pigs than in mice and rats probably reflected the larger reduction in blood osmolality in this species. In contrast to the findings of Trachtman et al. 25, it was obvious that no intraspecies correlation existed between brain Tau levels and specific gravities in acute hyposmolality. Control blood osmolality differed between mice, rats and guinea pigs. Since the brain osmolality is in (or close to) equilibrium with blood, the high specific gravity of the mouse cortex, and the low specific gravity of the guinea pig cortex, were expected. Free amino acids contribute marginally to plasma osmolality and negligibly to CSF and brain interstitial osmolality 6, but they constitute a significant fraction of osmolytes within neural cells. If their uneven inter- and intracellular distribution is disregarded TM, as well as their reduced osmotic activity caused by interaction with other solutes, amino acids make up at least 12% of the intracellular osmotic pressure of mouse cortex (tissue levels of amino acids approximate intracellular levels6). The corresponding figures for rats and guinea pigs are 11% and 8%, respectively. Contrary to expectation, there seemed to be an inverse relationship between a species' brain osmolality and Na + and K + concentrations. Presumably then, amino acids are particularly important as osmolytes in the

271 TABLE III Sodium and potassium content (mmol/lO0 g dry weighO of the cortex of mice, rats and guinea pigs injected with 150 ml/kg isotonic saline or distilled water

The concentration of Na ÷ and K + was determined by flame emission spectroscopy, ap < 0.05; bp < 0.01; cP < 0.001 (water-intoxicated vs control; Student's two-tailed t-test for unpaired observations). The results are means _+S.E.M. Electro-

tyte Na ÷ K÷

Mouse

Rat

Guinea pig

Saline

Water

% change Saline

Water

% change

Saline

Water

% change

19.1 + 0.3 48.6+0.8

17.2 + 0.3 b 46.8+1.0

-9.9 -3.5

16.7 + 0.7b 46.9+1.8 a

-19.7 -9.8

25.6 + 0.4 59.1_+0.3

21.8 + 0.4c 55.1+1.1 a

-14.8 -6.7

20.8 + 0.8 52.0+1.2

m o u s e brain, whereas they play a minor role in the guinea pig brain. T h e previously unknown relationship between brain w a t e r content and Tau concentration was, in face of the negative results with respect to the original aim of the study, the m a j o r finding. This correlation was also seen for Gin, but it was not as strong. The species differences in c e r e b r a l Tau levels have been known for many years (see ref. 26), but the reason for them has r e m a i n e d enigmatic. It was recently p o i n t e d out that there is an interspecies positive correlation between Tau concentration and c e r e b r a l glucose consumption 26. It was p r o p o s e d that Tau acts as an 'osmotic carrier' of water (osmotically drawn into neurons by glucose) from nerve cells to astrocytes. Incidentally, it was also suggested that Gln, which is p r e d o m i n a n t l y located in astrocytes, leaves the brain t o g e t h e r with osmotically obliged water 26. The p r e s e n t results offer a n o t h e r explanation for the species differences in cerebral [Tau], namely an association b e t w e e n Tau levels and brain water content (osmolality). D a t a on brain w a t e r and Tau content in rabbits 7'17 and toads 1 are in accordance with this proposal. Before discussing the effects of water intoxication, it should be r e m e m b e r e d that almost half of the mice r e n d e r e d hyposmotic died. It can therefore not be excluded that the results o b t a i n e d in mice were biased. A c u t e h y p o s m o l a l i t y p r o d u c e d multiple changes in cortical a m i n o acids. These alterations were largely speciesi n d e p e n d e n t and do not a p p e a r to be region-specific 1'11, at least not from a qualitative point of view. The possible pathophysiological implications of the amino acid der a n g e m e n t s in w a t e r - i n d u c e d cerebral e d e m a have been discussed elsewhere 1"11. REFERENCES 1 Baxter, C.E, Wasterlain, C.G., Hallden, K.L. and Pruess, S.E, Effect of altered blood plasma osmolalities on regional brain amino acid concentrations and focal seizure susceptibility in the rat, J. Neurochem., 47 (1986) 617-624. 2 del Rfo, R.M., Herranz, A.S., Herreras, O., Menendez, N. and Sol/s, J.M., Possible osmoregulatory role of taurine in the cellular swelling evoked by weak organic acids in the rat

Cortical e d e m a was associated with greater reductions in Na ÷ than in K ÷ in keeping with earlier work 15. This response is thought to reflect volume-regulatory mechanisms 15. Although there was no difference between the species studied in the severity of cortical swelling, the results suggest that the mechanism of protection against e d e m a is accomplished differently. The facts that the rat cortex swelled as much as the mouse cortex, while the content of Na ÷ and K ÷ was reduced twice as much in the rat compared with the mouse, indicate that the mouse depends more on organic osmolytes in the regulation of brain volume in acute hyposmolality. Consistent with this suggestion is the finding that the total concentration of amino acids decreased by 6.15 mmol/kg w.w. in the mouse cortex, whereas it only decreased by 1.11 mmol/kg w.w. in the rat cortex. In conclusion, the p r e s e n t results failed to reveal a relationship b e t w e e n cortical e d e m a and e n d o g e n o u s Tau levels. It m a y be speculated that the e n h a n c e d release of Tau from the hyposmotically swollen brain 12'21'27 reflects a vestige of a regulatory m e c h a n i s m 3-5 which has lost its physiological significance during the course of evolution. A l t e r n a t i v e l y , an o s m o e f f e c t o r function of Tau m a y be discernible only in mild 1° or chronic 25 hyposmolality. The present observation that Tau levels c o r r e s p o n d to brain water content in isosmotic conditions offers a clue to the large interspecies differences in this a m i n o acid.

Acknowledgements. We thank Dr. N.M. van Gelder for constructive criticism of the manuscript. This study was supported by grants from the Medical Research Council (B90-12X-09053-01A), Magn. Bergvalls Stiftelse, Adlerbertska Forskningsfonden, Kungl. och Hvitfeldtska Stipendieinrfittningen and Torsten och Ragnar S6derbergs Stiftelser (to A.L.). M.P. was partly supported by the Polish and Swedish Academies of Science.

hippocampus. In H. Pasantes-Morales, D.L. Martin, W. Shain and R.M. del Pdo (Eds.), Taurine: Functional Neurochemistry, Physiology, and Cardiology, Wiley-Liss, New York, 1990, pp. 357-368. 3 Forster, R.P. and Goldstein, L., Amino acids and cell volume regulation, Yale J. Biol. Med., 52 (1979) 497-515. 4 Fugelli, K. and Thoroed, S.M., Taurine transport associated with cell volume regulation in flounder erythrocytes under anisosmotic conditions, J. Physiol., 374 (1986) 245-261.

272 5 Goldstein, L., Brill, S.R. and Freund, E.V., Activation of taurine effiux in hypotonically stressed elasmobranch cells: inhibition by stilbene disulfonates, J. Exp. Zool., 254 (1990) 114-118. 6 Hamberger, A., Berthold, C.-H., Jacobson, I., Karlsson, B., Lehmann, A., Nystrrm, B. and Sandberg, M., In vivo brain dialysis of extraeellular non-transmitter and putative transmitter amino acids. In A. Bayrn and R. Drueker-Col/n (Eds.), In Vivo Perfusion and Release of Neuroactive Substances, Academic Press, New York, 1985, pp. 119-139. 7 Haug, P. and Nitsch, C., Increase in taurine content before onset of seizures induced by a glutamate decarboxylase inhibitor, Exp. Brain Res., 48 (1982) 463-466. 8 Johansson, B.B. and Linder, L.-E., Specific gravity of brain tissue during maturation. A comparison between neonatally 6-hydroxydopamine treated rats and controls, Acta Neurol. Scand., 66 (1982) 575-581. 9 Kimelberg, H.K., Goderie, S.K., Higman, S., Pang, S. and Waniewski, R.A., Swelling-induced release of glutamate, asparrate, and taurine from astrocyte cultures, J. Neurosci., 10 (1990) 1583-1591. 10 Law, R.O., Effects of pregnancy on the contents of water, taurine, and total amino nitrogen in rat cerebral cortex, J. Neurochem., 53 (1989) 300-302. 11 Lehmann, A., Carlstr6m, C., Nagelhus, E. and Ottersen, O.P., Elevation of taurine in hippocampal extracellular fluid and CSF of acutely hyposmotic rats: contribution by influx from blood?, J. Neurochem., in press. 12 Lehmann, A., Effects of microdialysis-perfusion with anisoosmotic media on extracellular amino acids in the rat hippocampus and skeletal muscle, J. Neurochem., 53 (1989) 525-535. 13 Lindroth, P., Sandberg, M. and Hamberger, A., Liquid chromatographic determination of amino acids after precolumn fluorescence derivatization. In A.A. Boulton, G.B. Baker and J.D. Wood (Eds.), Neuromethods: Amino Acids, Humana, Clifton, New Jersey, 1985, pp. 97-116. 14 Martin, D.L., Madelian, V., Seligmann, B. and Shain, W., The role of osmotic pressure and membrane potential in K +stimulated taurine release from cultured astrocytes and LRM55 cells, J. Neurosci., 10 (1990) 571-577. 15 Melton, J.E., Patlak, C.S., Pettigrew, K.D. and Cserr, H.E, Volume regulatory loss of Na, CI, and K from rat brain during acute hyponatremia, Am. J. Physiol., 252 (1987) F661-F669. 16 Nelson, S.R., Mantz, M.-L. and Maxwell, J.A., Use of specific gravity in the measurement of cerebral edema, J. Appl. Physiol., 30 (1971) 268-271.

17 Nitsch, C., Fujiwara, K. and Klatzo, I., Specific gravity increases and brain water content decreases during short epileptiform seizures in discrete rabbit brain areas, J. Neurol. Sci.. 64 (1984) 119-129.

18 Ottersen, O.P., Madsen, S., Storm-Mathisen, J., Somogyi, P., Scopsi, L. and Larsson, L.-I., Immunocytochemical evidence that taurine is co-localized with GABA in the Purkinje cell terminals, but that the stellate cell terminals predominantly contain GABA: a light- and electronmicroscopic study of the rat cerebellum, Exp. Brain Res., 72 (1988) 407-416. 19 Pasantes-Morales, H. and Schousboe, A., Release of taurine from astrocytes during potassium-evoked swelling, Glia, 2 (1989) 45-50. 20 Pasantes-Morales, H. and Schousboe, A., Volume regulation in astrocytes: a role for taurine as an osmoeffector?, J. Neurosci. Res., 20 (1988) 505-509. 21 Soils, J.M., Herranz, A.S., Herreras, O., Lerma, J. and del Rio, R.M., Does taurine act as an osmoregulatory substance in the rat brain?, Neurosci. Lett., 91 (1988) 53-58. 22 Thurston, J.H., Hauhart, R.E. and Dirgo, J.A., Taurine: a role in osmotic regulation of mammalian brain and possible clinical significance, Life Sci., 26 (1980) 1561-1568. 23 Thurston, J.H., Hauhart, R.E. and Nelson, J.S., Adaptive decreases in amino acids (taurine in particular), creatine, and electrolytes prevent cerebral edema in chronically hyponatremic mice: rapid correction (experimental model of central pontine myelinolysis) causes dehydration and shrinkage of brain, Metabol. Brain D/s., 2 (1987) 223-241. 24 Trachtman, H., Barbour, R., Sturman, J.A. and Finberg, L., Taurine and osmoregulation: taurine is a cerebral osmoprotecrive molecule in chronic hypernatremic dehydration, Pediatr. Res., 23 (1988) 35-39. 25 Trachtman, H., del Pizzo, R. and Sturman, J.A., Taurine and osmoregulation. III. Taurine deficiency protects against cerebral edema during acute hyponatremia, Pediatr. Res., 27 (1990) 85-88. 26 Van Gelder, N.M., Neuronal discharge hypersynchrony andthe intracranial water balance in relation to glutamic acid and taurine redistribution: migraine and epilepsy. In HI PasantesMorales, D.L. Martin, W. Shain and R.M. del Rio (Eds.), Taurine." Functional Neurochemistry, Physiology, and Cardiology, Wiley-Liss, New York, 1990, pp. 1-20. 27 Wade, J.V., Olson, J.P., Samson, EE., Nelson, S.R. and Pazdernik, T.L., A possible role for taurine in osmoregulation within the brain, J. Neurochem., 51 (1988) 740-745.

Species differences in cerebral taurine concentrations correlate with brain water content.

The notion that taurine (Tau) has an osmoregulatory function in the mammalian brain has not been established, although it has been reported that the s...
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