Brain Research, 99 (1975) 261-275 © Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
261
P E R T U R B A T I O N S IN F L U I D BALANCE I N D U C E D BY M E D I A L L Y PLACED F O R E B R A I N LESIONS
B. ANDERSSON, L. G. LEKSELL AND F. LISHAJKO
Department of Physiology I, Karolinska lnstitutet, S-10401 Stockholm 60 (Sweden) (Accepted May 29th, 1975)
SUMMARY
Acute and chronic effects on the fluid balance of radio-frequency forebrain lesions were studied in the goat. Medial lesions which involved practically the entire anterior wall of the third cerebral ventricle caused persistent loss of thirst and lack of significant antidiuretic hormone (ADH) release in response to hypernatraemia and plasma hyperosmo[ality. As acute response to such lesions an uncompensated, temporary water diuresis was seen, which rapidly caused pronounced hypernatraemia and hypovolaemia. Lesions extending laterally to encroach upon the supraoptic nuclei resulted in persistent signs of weak, inappropriate A D H secretion ( = impaired water diuresis, renal salt wasting, and pronounced hyponatraemia during hydration). Forebrain damage, mainly restricted to the septal region, caused hyperdipsia. In some goats, obvious post-lesioning increase in salt appetite was observed which could not be correlated to the extent of their forebrain damage. The results are discussed in relation to hypothalamic syndromes in man and previous studies on central control of fluid balance in the goat.
INTRODUCTION
Hypernatraemia associated with various kinds of damage to the hypothalamic region of the brain has been recognized in man since Allott 4 observed high serum sodium in patients with brain lesions at autopsy. This hypernatraemia has been attributed to abnormal renal sodium retention 11,31, but many later case reports indicate that it is secondary to decreased or absent thirst sensation appearing together with disturbances of the normal regulation of antidiuretic hormone (ADH) secretion (el refs. 20, 22 and 28). That damage to the hypothalamic region of the brain may induce hypernatraemia in combination with inadequate water intake in experimental animals was
262 first demonstrated by Stevenson29. He found that medially placed hypothalamic lesions induced hypodipsia and hypernatraemia in rats. Subsequent studies in the dog ~9,36, and in the goat 6 have demonstrated a complete and persistent loss of the urge to drink after extensive preoptic/anterior hypothalamic lesions. The preoptic/anterior hypothalamic region was selected also for the ablation studies reported here. However, the lesions were purposely restricted to the medial area of the goat's forebrain, since recent experiments in this species indicate that a sodium sensitive receptor system, located in the vicinity of the anterior portion of the third cerebral ventricle, participates in the control of water and salt balances (cf refs. 5 and 7). METHODS
Animals Thirteen female goats (pre-tesion body weight 33-42 kg) were used. The animals were routinely confined in metabolism cages (separating the urine from the feces) at a room temperature of 20 ~: 1 °C, where they had free access to chaffed hay and water, and received 400 g of commercial grain mix each afternoon. To maintain the goats in positive sodium balance, they were given 6 g of NaCI per day. Nine goats voluntarily drank the salt dissolved in 300 ml of warm water. The other 4 animals received the salt added to their daily ration of grain mix. The 24 h water intake and urine output were measured round 9 a.m. every morning and samples of the urine were taken for analyses.
Pre-lesioning preparations All goats had a pair of thermocouple electrodes (o.d. 0.7 mm) implanted through the septum into the preoptic/anterior hypothalamic region. The implantations were performed under general (Nembutal) anaesthesia about 3 weeks before the electrodes were used for production of radio-frequency (RF) lesions, For further details about the implantation and RF heating techniques see Gale 15. The two electrodes were either placed along the midline of the brain with an interspace of 2-4 mm, or bilaterally with an interspace of 2 or 3 mm, The length of the uninsulated ends of the electrodes varied between animals from 3 to 7 mm. Four of the goats had a polyvinyl catheter permanently implanted into the carotid artery as earlier described 1~.
Production of lesions Coagulative brain lesions were made by applying RF energy between the uninsulated ends of the thermocouple electrodes for 3--4 min. The temperature in the heated part of the forebrain was raised to a level of 60-65 °C. The coagulation was performed without anaesthesia with the goats standing in the metabolism cages having the urinary bladder catheterized. The RF heating was not seen to cause any pain or distress to the animals. The only effects observed during the actual heating were polypnoeic panting and, sometimes, an urge to drink.
263
Hydration and water supplementation Pre-lesioning hydration (in order to inhibit the A D H secretion) was accomplished by giving into the rumen by stomach tube 100 ml/kg of 38 °C water. Generally, a larger water load was needed to induce positive renal free water clearance (CH2o) after lesions had been placed in the forebrain. To prevent fatal dehydration, water was also administered by stomach tube to the animals which developed post-lesioning adipsia. Sampling and analyses To obtain clean urine samples during hydration experiments and on other occasions, the urine was collected via a retention catheter inserted into the urinary bladder. Blood samples (10 ml) were routinely taken from the jugular vein using a heparinized syringe. For determination of the hematocrit (Ht) values, the blood samples were centrifuged in graded tubes at 3500 rev./min for exactly 7 min. Urine and plasma [Na +] were determined by use of an EEL flame photometer, and an 'Advanced Instruments Inc.' osmometer was used for determinations of the osmolality of these fluids. A DH activity in the urine A D H activity in the urine was recovered and bioassayed as described by Lishajko and Andersson 21. Blood pressure and heart rate recordings In the 4 goats having a permanent polyvinyl catheter implanted into the carotid artery, the systolic/diastolic and the mean carotid blood pressures were occasionally recorded on an ink-writing polygraph after connection of the catheter to a Statham pressure transducer. The heart rate of the goats was determined by auscultation. Histology At the end of the post-lesioning observation periods, the goats were decapitated under Nembutal anaesthesia and the heads were perfused with physiological saline followed by 8 ~ formol saline. After formol fixation, a block of the brain, including the forebrain, the thalamus, and the hypothalamus, was embedded in celloidin and cut by serial transverse sectioning at 30 #m. The sections were stained either with toluidine blue or according to Loyez (see ref. 12). RESULTS
(A) Control studies The fluid balance was studied in all goats for periods of 7-18 days between the implantation of the electrodes and the RF-lesioning. The following data were obtained.
264 TABLE 1 PRE-LESION1NG BLOOD PLASMA VALUES IN NON-HYDRATED (WATER REPLETE) AND IN HYDRATED ~OATS
Non-hydrated Hydrated
Na ~ mEq/litre
Osmolality, mOsrnole/kg
Mean
Range
Mean
Range
145 141
142-149 138-143
298 291
294--303 288-294
No.
35 14
Water and salt turnover In each single animal the daily water intake remained rather constant during the control period (variation of intake ± 5 ml/kg day). However, large interindividual differences in the total intake were observed (range 30-60 ml/kg day), The urine output amounted to about 80 ~o of the water intake in the high-drinking animals, and at about 60 ~o of the intake in the low-drinking goats. The urine osmolality was inversely proportional to the urine output and ranged between 500 and 1800 mOsmole/kg. All goats showed day to day fluctuations in the renal Na + excretion, which varied between 20 and 180 mEq/day. Two or more blood samples were taken in each animal during the pre-lesioning balance studies. The plasma [Na +] and osmolality remained very stable and only small differences were seen between animals (Table I, 'nonhydrated'). Also, the Ht values remained stable in the single animal, but fairly large interindividual differences were observed (range 25-37). Effects of hydration The effect of hydration (100 ml/kg) was studied before the lesioning in 9 of the goats. All animals responded with a water diuresis which reached maximum level 1.5-2 h after water-loading (mean renal CH2O = + 5 mt/min, range +2.5 to + 7 ml/min). The hydration had no obvious effect on the renal Na + excretion which remained within the pre-hydration range (20-130/~ Eq/min) during the water diuresis. Blood samples, taken when the water diuresis was fully established, revealed about 5 ~ reduction of the Ht. The reduction of plasma [Na ÷] and osmolality was about 3 ~ (Table I, 'Hydrated'). Urinary ADH recovery In 6 of the goats (water replete, non-hydrated) 120 min samples of urine were collected for recovery and subsequent bioassay of ADH activity. The total ADH activity found in these samples corresponded to the antidiuretic activity of i-3 mU of arginine vasopressin. It indicated a basic neurohypophyseal ADH secretion within the range of 5-15 mU/h, since the urinary excretion ofcireuJating ADH apparently amounts to slightly more than 10~o of the ADH secretion in this species 21. (B) Lesion-induced distortions of the fluid balance (1) Regulation of water intake Adipsia. After lesioning, 5 of the goats showed complete and persistent lack of
265 the urge to drink water also when strongly dehydrated. The post-lesioning observation periods were 5 weeks to 3 months. All the animals voluntarily drank their daily salt supply dissolved in 300 ml of water, but refused to take pure water, even when water was offered to them in the same bowl as the salt solution. Two of the goats, having lesions which extended into the ventromedial part of the hypothalamus, developed hyperphagia, whereas the other 3 adipsic goats did not show any disturbance of the regulation of food intake. The body fluid condition of the adipsic animals was routinely controlled with frequent determinations of body weight and analyses of blood samples. By guidance of the results of these determinations, the estimated daily need for water was administered by stomach tube. However, the water supplementation was omitted for periods of 3-4 days on repeated occasions in each animal. As a result the goats lost about 10 ~ of their body weight and showed about 20 ~ increase in Ht concomitant with a rise of plasma [Na +] to about 180 mEq/litre and plasma osmolality to about 370 mOsmole/kg. At this degree of dehydration and hypovolaemia the heart rate of the goats had increased from a normal value of about 70 beats/rain to about 150 beats/rain. However, carotid blood pressure remained within the normal range (90-100 mm Hg) judging from recordings made in two of the goats. When dehydrated to this extent the goats still fed and behaved normally, apart from refusing to drink water. On no occasion was the dehydration carried any further.
sc
~'I t
4
~
5
Fig. 1. Forebrain damage (hatched areas) in common for the 5 goats in which the lesioning caused permanent loss of thirst and lack of significant ADH release in response to hypernatraemia and plasma hyperosmolality. Left: the brain damage projected on a drawing of a mid-sagittal section through the third cerebral ventricle (IlI) and its surroundings. Right: projections of the damage on 6 drawings of transverse sections corresponding to the numbered levels on the sagittal section. Abbreviations: AC, anterior commissure; CC, corpus callosum; CO, chiasma opticum; C M, corpus mammillare; F, descending column of the fornix; Ep, epiphysis; Hyp, hypophysis; LV, lateral ventricle; OT, optic tract; PVN, paraventricular nucleus; S, septal region; SC, supraoptic crest; SFO, subfornical organ; SON, supraoptic nucleus.
266 Hence, the possibility remains that emergency drinking might have appeared at: a more severe stage of dehydration and hypovolaemia in the 'adipsic' goats. In two animals 20 rain intracarotid infusions of 1 M NaCl (1.5 ml/min) had induced the drinking of 800 and 1000 ml of water before lesioning. Corresponding infusions made in these goats one week post-lesioning did not induce drinking. Histological examination of the brains of the 5 adipsic goats revealed medially located forebrain lesions with somewhat varying lateral extension. All lesions destroyed the anterior and anterio-dorsal wall of the third cerebral ventricle, including the lamina terminalis with the supraoptic crest, the midportion of the anterior commissure, and, in 3 animals, the entire subfornical organ. In two of the goats the most posterior part of the subfornical organ was not directly affected by the coagulation. However, in both these animals the septal tissue was destroyed immediately above the untouched, posterior portion of the subfornical organ. The brain damage in common for all the 5 adipsic goats is projected on sagittal and transverse sections in Fig. 1. A photograph of a transverse section through one of the lesions is shown in Fig. 2. Hypodipsia. In 3 goats (post-lesioning observation periods 3 weeks to 2 months) drinking was inadequate to maintain normal fluid balance after the lesioning. One of the goats did not drink for 9 days and had to be maintained on water by stomach tube during that period. The other two goats started to drink within 3 days after the lesioning. When no water supplementation was given, the hypodipsic goats remained hypernatraemic (plasma [Na +] 155-165 mEq]litre) with elevated plasma osmolality (310-330 mOsmole/kg). Histological examination of the brains showed that parts of the hatched area in Fig. 1 were undamaged. In one of the goats (having a complete destruction of the lamina terminalis, including the supraoptic crest) most of the subfornical organ, and the septal tissue above it, were left intact. In the other two goats the subfornical organ and the anterio-dorsal wall of the third ventricle were destroyed, but here the supraoptic crest and an additional part of the lamina terminalis remained intact. Hyperdipsia and changed drinking pattern. Somewhat unexpectedly, 3 goats (post-lesioning observations periods 4, 5 and 8 weeks) increased their water intake after the RF-coagulation. The animal studied for 5 weeks after the forebrain was lesioned had a rather high control water intake (58 ± 5 ml/kg/day). Nonetheless, it increased its intake from the day of the lesioning and onwards, drinking 85 ± 6 ml/kg throughout the post-lesioning observation period, and increasing its urinary output to the same extent. Judging from the Ht values the goat remained normovolaemic with normal plasma [Na +] and osmolality. In this animal the lesion had destroyed the entire subfornical organ and a large portion of the septum, but had left the lamina terminalis and the preoptic region in front of it intact. In the goat studied for 8 weeks after the lesioning, hyperdipsia developed slowly, and was preceded by marked hypodipsia during the first week when plasma [Na +] and osmolality were moderately elevated and Ht determinations indicated slight hypovotaemia. During the control period the water intake of this animal was 40 ± 4 ml/kg/day. The intake was reduced to 20 ± 4 ml/kg/day for 7 days after
267
Fig. 2. A transverse section (30/~m) at the level of the anterior commissure (AC) showing the radiofrequency lesion (RFL) in one of the adipsic goats. LV, lateral ventricle; 3, third ventricle: OT, optic tract. Staining: Loyez.
268
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261
P E R T U R B A T I O N S IN F L U I D BALANCE I N D U C E D BY M E D I A L L Y PLACED F O R E B R A I N LESIONS
B. ANDERSSON, L. G. LEKSELL AND F. LISHAJKO
Department of Physiology I, Karolinska lnstitutet, S-10401 Stockholm 60 (Sweden) (Accepted May 29th, 1975)
SUMMARY
Acute and chronic effects on the fluid balance of radio-frequency forebrain lesions were studied in the goat. Medial lesions which involved practically the entire anterior wall of the third cerebral ventricle caused persistent loss of thirst and lack of significant antidiuretic hormone (ADH) release in response to hypernatraemia and plasma hyperosmo[ality. As acute response to such lesions an uncompensated, temporary water diuresis was seen, which rapidly caused pronounced hypernatraemia and hypovolaemia. Lesions extending laterally to encroach upon the supraoptic nuclei resulted in persistent signs of weak, inappropriate A D H secretion ( = impaired water diuresis, renal salt wasting, and pronounced hyponatraemia during hydration). Forebrain damage, mainly restricted to the septal region, caused hyperdipsia. In some goats, obvious post-lesioning increase in salt appetite was observed which could not be correlated to the extent of their forebrain damage. The results are discussed in relation to hypothalamic syndromes in man and previous studies on central control of fluid balance in the goat.
INTRODUCTION
Hypernatraemia associated with various kinds of damage to the hypothalamic region of the brain has been recognized in man since Allott 4 observed high serum sodium in patients with brain lesions at autopsy. This hypernatraemia has been attributed to abnormal renal sodium retention 11,31, but many later case reports indicate that it is secondary to decreased or absent thirst sensation appearing together with disturbances of the normal regulation of antidiuretic hormone (ADH) secretion (el refs. 20, 22 and 28). That damage to the hypothalamic region of the brain may induce hypernatraemia in combination with inadequate water intake in experimental animals was
262 first demonstrated by Stevenson29. He found that medially placed hypothalamic lesions induced hypodipsia and hypernatraemia in rats. Subsequent studies in the dog ~9,36, and in the goat 6 have demonstrated a complete and persistent loss of the urge to drink after extensive preoptic/anterior hypothalamic lesions. The preoptic/anterior hypothalamic region was selected also for the ablation studies reported here. However, the lesions were purposely restricted to the medial area of the goat's forebrain, since recent experiments in this species indicate that a sodium sensitive receptor system, located in the vicinity of the anterior portion of the third cerebral ventricle, participates in the control of water and salt balances (cf refs. 5 and 7). METHODS
Animals Thirteen female goats (pre-tesion body weight 33-42 kg) were used. The animals were routinely confined in metabolism cages (separating the urine from the feces) at a room temperature of 20 ~: 1 °C, where they had free access to chaffed hay and water, and received 400 g of commercial grain mix each afternoon. To maintain the goats in positive sodium balance, they were given 6 g of NaCI per day. Nine goats voluntarily drank the salt dissolved in 300 ml of warm water. The other 4 animals received the salt added to their daily ration of grain mix. The 24 h water intake and urine output were measured round 9 a.m. every morning and samples of the urine were taken for analyses.
Pre-lesioning preparations All goats had a pair of thermocouple electrodes (o.d. 0.7 mm) implanted through the septum into the preoptic/anterior hypothalamic region. The implantations were performed under general (Nembutal) anaesthesia about 3 weeks before the electrodes were used for production of radio-frequency (RF) lesions, For further details about the implantation and RF heating techniques see Gale 15. The two electrodes were either placed along the midline of the brain with an interspace of 2-4 mm, or bilaterally with an interspace of 2 or 3 mm, The length of the uninsulated ends of the electrodes varied between animals from 3 to 7 mm. Four of the goats had a polyvinyl catheter permanently implanted into the carotid artery as earlier described 1~.
Production of lesions Coagulative brain lesions were made by applying RF energy between the uninsulated ends of the thermocouple electrodes for 3--4 min. The temperature in the heated part of the forebrain was raised to a level of 60-65 °C. The coagulation was performed without anaesthesia with the goats standing in the metabolism cages having the urinary bladder catheterized. The RF heating was not seen to cause any pain or distress to the animals. The only effects observed during the actual heating were polypnoeic panting and, sometimes, an urge to drink.
263
Hydration and water supplementation Pre-lesioning hydration (in order to inhibit the A D H secretion) was accomplished by giving into the rumen by stomach tube 100 ml/kg of 38 °C water. Generally, a larger water load was needed to induce positive renal free water clearance (CH2o) after lesions had been placed in the forebrain. To prevent fatal dehydration, water was also administered by stomach tube to the animals which developed post-lesioning adipsia. Sampling and analyses To obtain clean urine samples during hydration experiments and on other occasions, the urine was collected via a retention catheter inserted into the urinary bladder. Blood samples (10 ml) were routinely taken from the jugular vein using a heparinized syringe. For determination of the hematocrit (Ht) values, the blood samples were centrifuged in graded tubes at 3500 rev./min for exactly 7 min. Urine and plasma [Na +] were determined by use of an EEL flame photometer, and an 'Advanced Instruments Inc.' osmometer was used for determinations of the osmolality of these fluids. A DH activity in the urine A D H activity in the urine was recovered and bioassayed as described by Lishajko and Andersson 21. Blood pressure and heart rate recordings In the 4 goats having a permanent polyvinyl catheter implanted into the carotid artery, the systolic/diastolic and the mean carotid blood pressures were occasionally recorded on an ink-writing polygraph after connection of the catheter to a Statham pressure transducer. The heart rate of the goats was determined by auscultation. Histology At the end of the post-lesioning observation periods, the goats were decapitated under Nembutal anaesthesia and the heads were perfused with physiological saline followed by 8 ~ formol saline. After formol fixation, a block of the brain, including the forebrain, the thalamus, and the hypothalamus, was embedded in celloidin and cut by serial transverse sectioning at 30 #m. The sections were stained either with toluidine blue or according to Loyez (see ref. 12). RESULTS
(A) Control studies The fluid balance was studied in all goats for periods of 7-18 days between the implantation of the electrodes and the RF-lesioning. The following data were obtained.
264 TABLE 1 PRE-LESION1NG BLOOD PLASMA VALUES IN NON-HYDRATED (WATER REPLETE) AND IN HYDRATED ~OATS
Non-hydrated Hydrated
Na ~ mEq/litre
Osmolality, mOsrnole/kg
Mean
Range
Mean
Range
145 141
142-149 138-143
298 291
294--303 288-294
No.
35 14
Water and salt turnover In each single animal the daily water intake remained rather constant during the control period (variation of intake ± 5 ml/kg day). However, large interindividual differences in the total intake were observed (range 30-60 ml/kg day), The urine output amounted to about 80 ~o of the water intake in the high-drinking animals, and at about 60 ~o of the intake in the low-drinking goats. The urine osmolality was inversely proportional to the urine output and ranged between 500 and 1800 mOsmole/kg. All goats showed day to day fluctuations in the renal Na + excretion, which varied between 20 and 180 mEq/day. Two or more blood samples were taken in each animal during the pre-lesioning balance studies. The plasma [Na +] and osmolality remained very stable and only small differences were seen between animals (Table I, 'nonhydrated'). Also, the Ht values remained stable in the single animal, but fairly large interindividual differences were observed (range 25-37). Effects of hydration The effect of hydration (100 ml/kg) was studied before the lesioning in 9 of the goats. All animals responded with a water diuresis which reached maximum level 1.5-2 h after water-loading (mean renal CH2O = + 5 mt/min, range +2.5 to + 7 ml/min). The hydration had no obvious effect on the renal Na + excretion which remained within the pre-hydration range (20-130/~ Eq/min) during the water diuresis. Blood samples, taken when the water diuresis was fully established, revealed about 5 ~ reduction of the Ht. The reduction of plasma [Na ÷] and osmolality was about 3 ~ (Table I, 'Hydrated'). Urinary ADH recovery In 6 of the goats (water replete, non-hydrated) 120 min samples of urine were collected for recovery and subsequent bioassay of ADH activity. The total ADH activity found in these samples corresponded to the antidiuretic activity of i-3 mU of arginine vasopressin. It indicated a basic neurohypophyseal ADH secretion within the range of 5-15 mU/h, since the urinary excretion ofcireuJating ADH apparently amounts to slightly more than 10~o of the ADH secretion in this species 21. (B) Lesion-induced distortions of the fluid balance (1) Regulation of water intake Adipsia. After lesioning, 5 of the goats showed complete and persistent lack of
265 the urge to drink water also when strongly dehydrated. The post-lesioning observation periods were 5 weeks to 3 months. All the animals voluntarily drank their daily salt supply dissolved in 300 ml of water, but refused to take pure water, even when water was offered to them in the same bowl as the salt solution. Two of the goats, having lesions which extended into the ventromedial part of the hypothalamus, developed hyperphagia, whereas the other 3 adipsic goats did not show any disturbance of the regulation of food intake. The body fluid condition of the adipsic animals was routinely controlled with frequent determinations of body weight and analyses of blood samples. By guidance of the results of these determinations, the estimated daily need for water was administered by stomach tube. However, the water supplementation was omitted for periods of 3-4 days on repeated occasions in each animal. As a result the goats lost about 10 ~ of their body weight and showed about 20 ~ increase in Ht concomitant with a rise of plasma [Na +] to about 180 mEq/litre and plasma osmolality to about 370 mOsmole/kg. At this degree of dehydration and hypovolaemia the heart rate of the goats had increased from a normal value of about 70 beats/rain to about 150 beats/rain. However, carotid blood pressure remained within the normal range (90-100 mm Hg) judging from recordings made in two of the goats. When dehydrated to this extent the goats still fed and behaved normally, apart from refusing to drink water. On no occasion was the dehydration carried any further.
sc
~'I t
4
~
5
Fig. 1. Forebrain damage (hatched areas) in common for the 5 goats in which the lesioning caused permanent loss of thirst and lack of significant ADH release in response to hypernatraemia and plasma hyperosmolality. Left: the brain damage projected on a drawing of a mid-sagittal section through the third cerebral ventricle (IlI) and its surroundings. Right: projections of the damage on 6 drawings of transverse sections corresponding to the numbered levels on the sagittal section. Abbreviations: AC, anterior commissure; CC, corpus callosum; CO, chiasma opticum; C M, corpus mammillare; F, descending column of the fornix; Ep, epiphysis; Hyp, hypophysis; LV, lateral ventricle; OT, optic tract; PVN, paraventricular nucleus; S, septal region; SC, supraoptic crest; SFO, subfornical organ; SON, supraoptic nucleus.
266 Hence, the possibility remains that emergency drinking might have appeared at: a more severe stage of dehydration and hypovolaemia in the 'adipsic' goats. In two animals 20 rain intracarotid infusions of 1 M NaCl (1.5 ml/min) had induced the drinking of 800 and 1000 ml of water before lesioning. Corresponding infusions made in these goats one week post-lesioning did not induce drinking. Histological examination of the brains of the 5 adipsic goats revealed medially located forebrain lesions with somewhat varying lateral extension. All lesions destroyed the anterior and anterio-dorsal wall of the third cerebral ventricle, including the lamina terminalis with the supraoptic crest, the midportion of the anterior commissure, and, in 3 animals, the entire subfornical organ. In two of the goats the most posterior part of the subfornical organ was not directly affected by the coagulation. However, in both these animals the septal tissue was destroyed immediately above the untouched, posterior portion of the subfornical organ. The brain damage in common for all the 5 adipsic goats is projected on sagittal and transverse sections in Fig. 1. A photograph of a transverse section through one of the lesions is shown in Fig. 2. Hypodipsia. In 3 goats (post-lesioning observation periods 3 weeks to 2 months) drinking was inadequate to maintain normal fluid balance after the lesioning. One of the goats did not drink for 9 days and had to be maintained on water by stomach tube during that period. The other two goats started to drink within 3 days after the lesioning. When no water supplementation was given, the hypodipsic goats remained hypernatraemic (plasma [Na +] 155-165 mEq]litre) with elevated plasma osmolality (310-330 mOsmole/kg). Histological examination of the brains showed that parts of the hatched area in Fig. 1 were undamaged. In one of the goats (having a complete destruction of the lamina terminalis, including the supraoptic crest) most of the subfornical organ, and the septal tissue above it, were left intact. In the other two goats the subfornical organ and the anterio-dorsal wall of the third ventricle were destroyed, but here the supraoptic crest and an additional part of the lamina terminalis remained intact. Hyperdipsia and changed drinking pattern. Somewhat unexpectedly, 3 goats (post-lesioning observations periods 4, 5 and 8 weeks) increased their water intake after the RF-coagulation. The animal studied for 5 weeks after the forebrain was lesioned had a rather high control water intake (58 ± 5 ml/kg/day). Nonetheless, it increased its intake from the day of the lesioning and onwards, drinking 85 ± 6 ml/kg throughout the post-lesioning observation period, and increasing its urinary output to the same extent. Judging from the Ht values the goat remained normovolaemic with normal plasma [Na +] and osmolality. In this animal the lesion had destroyed the entire subfornical organ and a large portion of the septum, but had left the lamina terminalis and the preoptic region in front of it intact. In the goat studied for 8 weeks after the lesioning, hyperdipsia developed slowly, and was preceded by marked hypodipsia during the first week when plasma [Na +] and osmolality were moderately elevated and Ht determinations indicated slight hypovotaemia. During the control period the water intake of this animal was 40 ± 4 ml/kg/day. The intake was reduced to 20 ± 4 ml/kg/day for 7 days after
267
Fig. 2. A transverse section (30/~m) at the level of the anterior commissure (AC) showing the radiofrequency lesion (RFL) in one of the adipsic goats. LV, lateral ventricle; 3, third ventricle: OT, optic tract. Staining: Loyez.
268
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