Investigating structural brain changes of dehydration using voxel-based morphometry.

Dehydration can affect the volume of brain structures, which might imply a confound in volumetric and morphometric studies of normal or diseased brain. Six young, healthy volunteers were repeatedly investigated using three-dimensional T(1)-weighted magnetic resonance imaging during states of normal hydration, hyperhydration, and dehydration to assess volume changes in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The datasets were analyzed using voxel-based morphometry (VBM), a widely used voxel-wise statistical analysis tool, FreeSurfer, a fully automated volumetric segmentation measure, and SIENAr a longitudinal brain-change detection algorithm. A significant decrease of GM and WM volume associated with dehydration was found in various brain regions, most prominently, in temporal and sub-gyral parietal areas, in the left inferior orbito-frontal region, and in the extra-nuclear region. Moreover, we found consistent increases in CSF, that is, an expansion of the ventricular system affecting both lateral ventricles, the third, and the fourth ventricle. Similar degrees of shrinkage in WM volume and increase of the ventricular system have been reported in studies of mild cognitive impairment or Alzheimer's disease during disease progression. Based on these findings, a potential confound in GM and WM or ventricular volume studies due to the subjects' hydration state cannot be excluded and should be appropriately addressed in morphometric studies of the brain.

Cerebrospinal fluid formation and absorption in dehydrated sheep.

Cerebrospinal fluid (CSF) plays an important role in the brain's adaptive response to acute osmotic disturbances. In the present experiments, the effect of 48-h dehydration on CSF formation and absorption rates was studied in conscious adult sheep. Animals had cannulas chronically implanted into the lateral cerebral ventricles and cisterna magna to enable the ventriculocisternal perfusion. A 48-h water deprivation altered neither CSF production nor resistance to CSF absorption. However, in the water-depleted sheep, intraventricular pressure tended to be lower than that found under control conditions. This likely resulted from decreased extracellular fluid volume and a subsequent drop in central venous pressure occurring in dehydrated animals. In conclusion, our findings provide evidence for the maintenance of CSF production during mild dehydration, which may play a role in the regulation of fluid balance in the brain during chronic hyperosmotic stress.

Continuous measurement of Na concentration in CSF during gastric water infusion in dehydrated rats.

To assess the differential stimulus to central and intravascular osmoreceptors during recovery from thermal dehydration, we measured Na concentrations in cerebrospinal fluid ([Na]CSF) and plasma ([Na]p) continuously and compared these during simulated drinking by gastric water infusion (INF) in euhydrated and thermally dehydrated rats under anesthesia. Continuous measurement of [Na]CSF was obtained with a double-barreled Na electrode placed in the lateral ventricle. Continuous measurement of [Na]p was obtained from a flow cell Na electrode in an extracorporeal shunt. Measurements were made during 10 min of INF (2.5 ml/100 g body wt) into the stomach and during 20 min of recovery. Changes in [Na]CSF always lagged behind those in [Na]p and were quantitatively smaller after INF. The decrease in [Na]CSF occurred sooner in dehydrated than in euhydrated rats in response to the decrease in [Na]p (P < 0.01). These results suggest that water and/or Na movement between blood and CSF is accelerated during restitution from thermal dehydration, acting to prevent overhydration during the early phase of rehydration.

Vasopressin levels in the cerebrospinal fluid of rats with lesions of the paraventricular and suprachiasmatic nuclei.

The circadian rhythm and dehydration-induced response of vasopressin (AVP) levels in rat cerebrospinal fluid (CSF) were studied after lesions had been made in the paraventricular (PVN) and suprachiasmatic (SCN) nuclei. The rhythmic fluctuation of AVP levels in CSF was abolished after SCN lesions, whereas lesions of the PVN had no effect. Dehydration seems to increase AVP levels in CSF of both sham-operated and lesioned animals. These data further suggest that the circadian rhythm of AVP in CSF is preferentially generated by SCN. In contrast, several areas of the brain may contribute to the overall AVP levels in CSF, both under normal physiological conditions and under osmotic stress.

Dehydration and arginine vasotocin and angiotensin II in CSF and plasma of pekin ducks.

Osmolalities and, by radioimmunoassay, the contents of arginine vasotocin (AVT) and angiotensin II (ANG II) in simultaneously collected cisternal cerebrospinal fluid (CSF) and plasma samples were determined in chronically prepared conscious Pekin ducks (Anas platyrhynchos) adapted to either freshwater (FW ducks) or salt water (2% saline, SW ducks) for drinking. In FW ducks the AVT in CSF was approximately 10-fold higher than in plasma; ANG II concentration in CSF was about two-thirds of that in plasma. In SW ducks concentrations of AVT were increased approximately threefold and of ANG II fourfold in both CSF and plasma. Dehydration in FW ducks (24-48 h) increased AVT and ANG II in both CSF and plasma, the relative rise being greater in plasma. Within 150 min after rehydration plasma AVT fell at unchanged CSF AVT, whereas CSF ANG II fell at unchanged plasma ANG II. Hydration of SW ducks with freshwater had similar effects. The results indicate separate avenues of release of central and systemic AVT and ANG II and support the idea of an independent control of central ANG II as a mediator in osmoregulation, with CSF AVT reflecting the state of osmoregulatory activity of the hypothalamopituitary vasotocinergic system.

Inhibition of dehydration induced drinking in rats by reduction of CSF Na concentration.

Male rats were dehydrated for 22 h and then given 4 h intracerebroventricular (i.c.v.) infusions which commenced 2 h prior to the beginning of a 2-h fluid access period. I.c.v. infusion of iso-osmotic 0.27 M mannitol-CSF more than halved the amount of water normally drunk by dehydrated rats during the fluid access period. Whilst i.c.v. infusion of 0.7 M mannitol-CSF did not alter the amount of water drunk during the fluid access period. Presumably both infusates reduce CSF [Na] but only 0.7 M mannitol elevates CSF osmolality. The evidence is consistent with the involvement of both sodium and osmoreceptors in thirst in the rat. A reduction of CSF [Na] will inhibit dehydration induced water drinking provided the osmotic pressure of the CSF is not greatly elevated. In addition evidence is provided to show that a contrived reduction of CSF [Na] alone is not a sufficient physiological trigger to initiate salt appetite in rats.

Independent osmoregulatory control of central and systemic angiotensin II concentrations in dogs.

In 14 dogs angiotensin (ANG II)-like immunoreactivity was analyzed in simultaneously collected samples of cerebrospinal fluid (CSF) from the anterior part of the third cerebral ventricle and of plasma. Plasma and CSF ANG II were not different in euhydrated conscious dogs (29.3 +/- 2.7 and 30.8 +/- 2.8 pg X ml-1, means +/- SE). During anesthesia CSF ANG II was not significantly altered, but plasma ANG II was more than doubled in comparison with conscious animals. In conscious dogs 24 h of dehydration with sodium-rich food significantly increased ANG II concentration in the plasma (to 59.8 +/- 16.5 pg X ml-1) and CSF (to 71.8 +/- 20.1 pg X ml-1). Subsequent rehydration by drinking caused no consistent changes in plasma ANG II within 90 min but reduced CSF ANG II significantly. Salt loading by infusion of 5% saline in seven conscious dogs produced a small but consistent decrease in plasma ANG II by 20%, on average, whereas CSF ANG II rose in five animals. The directions of changes in concentration of central ANG II compared with plasma ANG II suggest that central endogenous ANG II may function as a central osmoregulatory mediator independent from systemic ANG II.

Acid base balance in blood and cerebrospinal fluid.

Thirty four infants were studied; 21 with acute gastroenteritis, dehydration, and metabolic acidosis and 13 who served as controls. All infants with metabolic acidosis and without neurological signs had a normal to near normal cerebrospinal fluid acid base balance, but five with metabolic acidosis and severe neurological signs had cerebrospinal fluid acid base disequilibrium. Acute metabolic acidosis in infants may lead to cerebrospinal fluid acid base imbalance causing cerebral dysfunction.

Vasopressin in plasma and ventricular cerebrospinal fluid during dehydration, postural changes, and nausea.

The responses of plasma and ventricular cerebrospinal fluid (CSF) vasopressin concentration to dehydration, postural changes, and induction of nausea were studied in 21 patients with hydrocephalus of various etiology. The 24-h dehydration test evoked a significant increase in plasma osmolality and vasopressin concentration, whereas the concentration of vasopressin in CSF was unchanged. Head-up tilt to 50 degrees for 45 min with a tilt bed resulted in a modest increase of plasma vasopressin in patients who did not develop presyncopal symptoms, but no changes were seen in CSF vasopressin. Induction of nausea by subcutaneously injected apomorphine provoked a marked (20- to 50-fold) rise in plasma vasopressin concentration within 15 min, and the plasma concentration was significantly increased above base-line values for 60-120 min. Despite the prolonged period of high plasma vasopressin concentration CSF vasopressin was not influenced by the apomorphine injection. The findings suggest that the concentration of vasopressin in the CSF is controlled by mechanisms other than the well-known osmotic and nonosmotic stimuli of vasopressin release into the blood.

Plasma and cerebrospinal fluid vasopressin and osmolality in relation to thirst.

Conscious dogs chronically implanted with a device for cerebrospinal fluid (CSF) sampling from the anterior 3rd ventricle were submitted to 24 h dehydration. During rehydration by drinking the total water intake ( TWI ) after 16 min was determined in 8 and after 90 min in 14 experiments. Samples were simultaneously drawn to determine the osmolalities (Posm, CSFosm ) and AVP concentrations (PAVP, CSFavp ) of plasma and CSF. After 24 h dehydration all of these parameters were significantly elevated in comparison to euhydrated dogs investigated on 19 occasions. In 8 experiments 60% of the final TWI had been ingested within the first 16 min with no changes of Posm, CSFosm and CSFAVP , but a significant decrease of PAVP at this time. TWI per kg body weight ( TWI X kg-1) after 90 min was significantly correlated with the osmolalities and AVP levels in plasma and CSF prior to rehydration. The decreases of Posm, CSFosm and PAVP, but not of CSFAVP , were significantly correlated with TWI X kg-1. The results indicate that PAVP and CSFAVP are subject to long term control by body fluid tonicity exhibiting a feedback relationship to water intake. In addition, PAVP but not CSFAVP seems to be under short term, possibly nonosmotic, control during water intake.

Osmolar relationships in infantile dehydration.

We studied serum osmolality in 167 consecutive infants admitted for gastroenteritis with 5% or more dehydration. Osmolality was determined by the freezing-point method in a 0.2-mL sample of serum immediately on admission. Forty-one patients (24.6%) had hypo-osmolar dehydration, with a mean osmolality of 257 mOsm/kg (range, 234 to 270 mOsm/kg). Eleven patients (6.5%) had hyperosmolar dehydration, with a mean osmolality of 329 mOsm/kg (range, 312 to 369 mOsm/kg). Simultaneous serum and CSF osmolalities were determined in 14 patients with hypo-osmolar and eight with hyperosmolar dehydration. In patients with hyperosmolar dehydration, serum osmolality correlated well with CSF osmolality, but a poor correlation was seen between serum and CSF sodium levels. Convulsions occurred in two patients in whom the CSF osmolality was greater than the serum osmolality by more than 10 mOsm/kg. Convulsions also occurred in two patients with hypo-osmolar dehydration in whom the CSF osmolality was lower than the serum osmolality by more than 13 mOsm/kg.

Osmolar relation between cerebrospinal fluid and serum in hyperosmolar hypernatraemic dehydration.

The relation between cerebrospinal fluid (CSF) and serum osmolality was studied in 16 patients with hyperosmolar hypernatraemic dehydration before treatment. After correcting shock and acidosis, 0-45% saline in 2-5 or 5% dextrose was infused in each patient over a 48- to 72-hour period. During rehydration, serum osmolality, electrolyte concentrations, urea nitrogen, and blood pH were measured sequentially. Five patients developed severe neurological abnormalities within 48 hours of addmission (convulsions 2, convulsions with hemiplegia 2, hemiplegia 1). Of these, 3 had residual defects on follow-up at least one year later. This group was indistinguishable from the 11 without significant neurological abnormality, both on clinical grounds before rehydration, and after analysis of admission and subsequent serum biochemical variables. A significant osmolar gap (greater than 4 mmol/kg H2O) between serum and CSF was found in 13 patients. Severe neurological disturbance only occurred when CSF osmolality exceeded that of serum by 7 or more mmol/kg H2O. Discriminant analysis of the paired osmolar data showed that D = -117+1-74 X(CSF osmolality) -1-41 X (serum osmolality), and that severe neurological abnormality was predicted when D was positive.