Cerebrospinal Fluid Hypernatremia Elevates Sympathetic Nerve Activity and Blood Pressure via the Rostral Ventrolateral Medulla.

Elevated NaCl concentrations of the cerebrospinal fluid increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. Neurons of the rostral ventrolateral medulla (RVLM) play a pivotal role in the regulation of SNA and receive mono- or polysynaptic inputs from several hypothalamic structures responsive to hypernatremia. Therefore, the present study investigated the contribution of RVLM neurons to the SNA and pressor response to cerebrospinal fluid hypernatremia. Lateral ventricle infusion of 0.15 mol/L, 0.6 mol/L, and 1.0 mol/L NaCl (5 µL/10 minutes) produced concentration-dependent increases in lumbar SNA, adrenal SNA, and arterial blood pressure, despite no change in splanchnic SNA and a decrease in renal SNA. Ganglionic blockade with chlorisondamine or acute lesion of the lamina terminalis blocked or significantly attenuated these responses, respectively. RVLM microinjection of the gamma-aminobutyric acid (GABAA) agonist muscimol abolished the sympathoexcitatory response to intracerebroventricular infusion of 1 mol/L NaCl. Furthermore, blockade of ionotropic glutamate, but not angiotensin II type 1, receptors significantly attenuated the increase in lumbar SNA, adrenal SNA, and arterial blood pressure. Finally, single-unit recordings of spinally projecting RVLM neurons revealed 3 distinct populations based on discharge responses to intracerebroventricular infusion of 1 mol/L NaCl: type I excited (46%; 11/24), type II inhibited (37%; 9/24), and type III no change (17%; 4/24). All neurons with slow conduction velocities were type I cells. Collectively, these findings suggest that acute increases in cerebrospinal fluid NaCl concentrations selectively activate a discrete population of RVLM neurons through glutamate receptor activation to increase SNA and arterial blood pressure.

Adipsic hypernatremia in a dog with antithyroid antibodies in cerebrospinal fluid and serum.

A 4-year-old, male Labrador retriever, weighing 27 kg, presented with abrupt clinical signs including mental retardation, circling and head pressing. The dog never ingested water by choice. An adipsia of the dog was persisted and developed to hypernatremia with artifactual hyperchloremia. Serial endocrine results and image findings were suggestive of a hypothyroidism. The dog revealed the presence of antithyroid antibodies in the cerebrospinal fluid and serum. With the administration of levothyroxine sodium, his neurologic signs were alleviated within the first week of treatment and adipsia was also resolved.

Changes in Na concentration in cerebrospinal fluid during acute hypernatremia and their effect on drinking in juvenile rats.

To clarify if there are age-related differences in osmoreception, we measured changes in Na concentration in cerebrospinal fluid ([Na]csf) during and after acute hypernatremia in juvenile (JR) and adult rats (AR). The Na concentrations in plasma ([Na]pl) and [Na]csf were measured during intravenous infusion of 1 M NaCl solution (INF, 0.2 ml/100 g body wt. for 10 min) and for 20 min thereafter in anesthetized rats. To measure [Na]pl, a flow-through Na-sensitive electrode was placed in an extracorporeal shunt from a carotid artery to a jugular vein, and to measure [Na]csf, a Na-sensitive electrode was placed in the right lateral ventricle. There was a linear relationship between delta[Na]pl and delta[Na]csf during INF. The slope of delta[Na]pl vs. delta[Na]csf was 0.42 +/- 0.03 (n = 7) in JR, which was significantly higher (p less than 0.01) than in AR (0.23 +/- 0.04, n = 6). We also measured water intake during and after INF of the same amount of 1 M NaCl solution in conscious JR (n = 6) and AR (n = 6). The JR drank 1.93 +/- 0.22 ml/100 g body wt. of water within 30 min of the start of INF, which was significantly more (p less than 0.05) than AR drank (1.20 +/- 0.13 ml/100 g body wt.). These results indicate that the movement of Na or water, or both, between the blood and cerebrospinal fluid in acute hypernatremia is greater in JR, and that the osmoreceptors in JR are more sensitive than those in AR.

Hypernatremic dehydration with hemorrhage into the choroid plexus.

A 2 1/2-month-old patient is reported with computed tomographic evidence of bilateral choroid plexus hemorrhage associated with hypernatremic dehydration. Choroid plexus hemorrhage may have caused increased cerebrospinal fluid protein observed in hypernatremic dehydration, as well as intraventricular hemorrhage.

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.

The effect of chronic osmotic disturbance on the concentrations of cations in cerebrospinal fluid.

1. Adult cats were rendered hypo- and hypernatraemic by peritoneal dialysis. These states were maintained for periods of 2-5 days.2. The concentrations in cerebrospinal fluid (c.s.f.) of the cations, potassium, calcium and magnesium all decreased in the hyponatraemic animals and increased in the hypernatraemic animals. These shifts in c.s.f. cation concentrations did not relate to plasma changes in the same cations, which were often in the opposite direction.3. The relations of the cation concentrations to c.s.f. sodium were not linear and, in the cases of calcium and magnesium, the relevant cation concentration related better to the square rather than the first power of the c.s.f. sodium concentration.4. Brain water changed much less in the hypo- and hypernatraemic animals than might be anticipated from the shifts in blood osmolarity, plasma sodium concentration and muscle water.5. Isotonicity of the fluids in brain with blood plasma and c.s.f. appeared to be largely maintained by loss or gain of sodium and chloride ions by this tissue.6. The c.s.f. results may be partly due to a constant influx of the cation in question being diluted with more formed c.s.f. in hyponatraemia and less c.s.f. in hypernatraemia, but the deviations from linearity in the plots of c.s.f. cation against c.s.f. sodium suggest the influence of other factors.