Perturbations in fluid balance induced by medially placed forebrain lesions

doi:10.1016/0006-8993(75)90028-1

Brain Research

Volume 99, Issue 2, 5 December 1975, Pages 261-275

https://doi.org/10.1016/0006-8993(75)90028-1 Get rights and content

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 hyperosmolality. 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 ADH secretion ( double bond 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.

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Relative to our sheep, more extensive lateral septal lesions in rats did cause hyperdipsia for 15 days, possibly related to impaired vasopressin secretion that was observed (Iovino and Steardo, 1985). The common tissue ablated in 3 goats that caused hyperdipsia was also mainly in the medial septum and more medial parts of the lateral septum (Andersson et al., 1975). Such lesions suggest that an inhibitory influence on thirst either arises in the medial septal nucleus, or is being transmitted via a neural pathway passing through this region; electrolytic lesions do not allow distinctions to be drawn in this regard.
Previous experiments in rodents showed that ablation of the septal brain region caused hyperdipsia. We investigated which part of the septal region needs ablation to produce hyperdipsia in sheep, and whether increased drinking was a primary hyperdipsia. Following ablation of the medial septal region (n = 5), but not parts of the lateral septal region (n = 4), daily water intake increased from ~2.5–5 L/day up to 10 L/day for up to 3 months post-lesion. In hyperdipsic sheep, plasma osmolality increased on the first day post-lesion and body weight fell, suggesting that initial hyperdipsia was secondary to fluid loss. However hyperosmolality was not sustained long-term and plasma hypo-osmolality persisted from 0.5 to 3 months post-lesion. Acute dipsogenic responses to intravenous hypertonic saline, intravenous or intracerebroventricular angiotensin II, water deprivation for 2 days, or feeding over 5 h were not potentiated by medial septal lesions, showing that the rapid pre-systemic inhibitory influences that cause satiation of thirst upon the act of drinking were intact. However, hyperdipsic sheep continued to ingest water when hyponatremic (plasma [Na] was 127–132 mmol/l) and plasma osmolality was 262–268 mosmol/kg due to retention of ingested fluid resulting from intravenous infusion of vasopressin administered to maintain a basal blood level of antidiuretic hormone. The results show that septal lesion-induced hyperdipsia is not due to disruption of acute pre-systemic influences associated with drinking water that initiates rapid satiation of thirst. Rather, inhibitory influences of hyponatremia, hypo-osmolality or hypervolemia on drinking appear to be disrupted by medial septal lesions.
The median preoptic nucleus: A major regulator of fluid, temperature, sleep, and cardiovascular homeostasis
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It is also likely that Na+ sensors within MnPO (Grob et al., 2004b) have a role in vasopressin release. In regard to the inhibitory GABAergic input from the MnPO to vasopressin-secreting neurons in the hypothalamic supraoptic and paraventricular nuclei (Nissen and Renaud, 1994; Abbott et al., 2016), studies in goats and rats in which the lamina terminalis was ablated have shown that the excretion of water loads is impaired if the MnPO is included in the lesion (Andersson et al., 1975; Johnson et al., 1978; Rundgren and Fyhrquist, 1978). These observations suggest that an impairment in inhibition of vasopressin secretion was caused by ablating the MnPO, despite the fact that excitatory glutamatergic input from MnPO to vasopressin-secreting neurons in the PVH and supraoptic nucleus would have been destroyed.
Located in the midline lamina terminalis of the anterior wall of the third ventricle, the median preoptic nucleus is a thin elongated nucleus stretching around the rostral border of the anterior commissure. Its neuronal elements, composed of various types of excitatory glutamatergic and inhibitory GABAergic neurons, receive afferent neural signals from (1) neighboring subfornical organ and organum vasculosum of the lamina terminalis related to plasma osmolality and hormone concentrations, e.g., angiotensin II; (2) from peripheral sensors such as arterial baroreceptors and cutaneous thermosensors. Different sets of these MnPO glutamatergic and GABAergic neurons relay output signals to hypothalamic, midbrain, and medullary regions that drive homeostatic effector responses. Included in the effector responses are (1) thirst, antidiuretic hormone secretion and renal sodium excretion that subserve osmoregulation and body fluid homeostasis; (2) vasoconstriction or dilatation of skin blood vessels, and shivering and brown adipose tissue thermogenesis for core temperature homeostasis; (3) inhibition of hypothalamic and midbrain nuclei that stimulate wakefulness and arousal, thereby promoting both REM and non-REM sleep; and (4) activation of sympathetic pathways that drive vasoconstriction and heart rate to maintain arterial pressure and the perfusion of vital organs. The small size of MnPO belies its massive homeostatic significance.
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In parallel to gain-of-function studies, several loss-of-function techniques have been employed in the past few decades to study the functional necessity of a given neural circuit (Table 2). Early studies demonstrated that radio-frequency lesions of forebrain areas including the LT disrupted fluid balance and thirst mechanisms in goats [34] and rats [35,36]. The physical destruction of the neural connection between the SFO and MnPO has been shown to attenuate water intake in rats [37,38].
Fine balance between loss-of water and gain-of water is essential for maintaining body fluid homeostasis. The development of neural manipulation and mapping tools has opened up new avenues to dissect the neural circuits underlying body fluid regulation. Recent studies have identified several nodes in the brain that positively and negatively regulate thirst. The next step forward would be to elucidate how neural populations interact with each other to control drinking behavior.
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Later work [107–109] further indicated the potential presence of both osmoreceptors and Na+ receptors, and that these receptors must be within an area lacking a BBB, (predictions which have been shown to be accurate — see Section 4, Sensory abilities of CVO cells). Lesions to the AV3V inhibited drinking and antidiuresis brought about by the injection of hypertonic stimulus [110,111]. More recent work has indicated that combining OVLT lesions with lesions affecting SFO and MnPO (not a CVO) further inhibit osmotic stimulated drinking [112].
Sensory circumventricular organs (CVOs) are specialized areas of the brain that lack a normal blood–brain barrier, and therefore are in constant contact with signaling molecules circulating in the bloodstream. Neurons of the CVOs are well endowed with a wide spectrum of receptors for hormones and other signaling molecules, and they have strong connections to hypothalamic and brainstem nuclei. Therefore, lying at the blood–brain interface, the sensory CVOs are in a unique position of being able to detect and integrate humoral and neural information and relay the resulting signals to autonomic control centers of the hypothalamus and medulla. This review focuses primarily on the roles played by the sensory CVOs in fluid balance and energy metabolism.

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Perturbations in fluid balance induced by medially placed forebrain lesions

Summary

Amer. J. Med.

Lancet

Lancet

Amer. J. Med.

Recent Progr. Hormone Res.

Brain Research

Das Subfornikalorgan: morphologische Untersuchungen mit besonderer Berücksichtigung der cholinergen Innervation und der neurosekretorischen Aktivität

Schweiz. Arch. Neurol. Psychiat.

Subfornical organ and cholinergic activity

Thirst — and brain control of water balance

Amer. Scientist

Influence of local temperature changes in the preoptic area and rostral hypothalamus on the regulation of food and water intake

Acta physiol. scand.

On central control of body fluid homeostasis

Condit. Reflex

The syndrome of inappropriate secretion of antidiuretic hormone

Amer. J. Med.

Primary hyperdipsia in the rat following septal lesions

J. comp. physiol. Psychol.

Inappropriate antidiuretic hormone secretion (hypothalamic glioma in a child)

Arch. Neurol. (Chic.)

Salt appetite

Differences in the antidiuretic response to intracarotid infusions of various hypertonic solutions in the conscious goat

Acta physiol. scand.

Non-essential role of prolactin in the hormonal restoration of lactation in goats with radio frequency hypothalamic lesions

Acta physiol. scand.