Homeostasis and the concept of 'interstitial fluids hierarchy': Relevance of cerebrospinal fluid sodium concentrations and brain temperature control (Review)

Abstract

In this review, the aspects and further developments of the concept of homeostasis are discussed also in the perspective of their possible impact in the clinical practice, particularly as far as psychic homeostasis is concerned. A brief historical survey and comments on the concept of homeostasis and allostasis are presented to introduce our proposal that is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. However, the new concept of a hierarchic role of ISF of the various organs is introduced. Additionally, it is suggested that particularly for some chemico-physical parameters, oscillatory rhythms within their proper set-ranges should be considered a fundamental component of homeostasis. Against this background, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment, not simply for brain cell survival, but also for brain complex functions and the oscillatory rhythms of some parameters, such as cerebrospinal fluid sodium and brain ISF pressure waves, which may play a crucial role in brain physio-pathological states. Thus, according to this proposal, the brain ISF represents the real internal medium since the maintenance of its dynamic intra-set-range homeostasis is the main factor for a free and independent life of higher vertebrates. Furthermore, the evolutionary links between brain and kidney and their synergistic role in H2O/Na balance and brain temperature control are discussed. Finally, it is surmised that these two interrelated parameters have deep effects on the Central Nervous System (CNS) higher integrative actions such those linked to psychic homeostasis.

On the physiological and cellular homeostasis of ascorbate

“…There is however an important exceptionthe brain, where autonomous interstitial fluid is surrounded by tightly packed endothelial barriers [23,35,49]. This allows the ascorbate concentration in interstitial fluids of the brain to be maintained at the level of 0.5 mM [50]. Ascorbate is extracted from interstitial fluids by cells into their cytoplasm by high affinity/low capacity SVCT2 transporters [20,[51][52][53].…”

“…Secondly, the physiological arrangement of ascorbate transporters ensures its low interstitial ascorbate concentration, thus limiting the risk of generation of a significant quantity of toxic labile transition metals [59,60]. The ascorbate homeostasis in interstitial fluids (deficient in humans) provides a uniform baseline against which all other cells adjust their cytoplasmic concentrations by simply controlling the number of SVCT2 transporters [50]. Therefore, the ascorbate deficiency will affect interstitial compartments first.…”

In vitro toxicity model: Upgrades to bridge the gap between preclinical and clinical research

“…Extracellular fluid, especially interstitial fluid (IF), interacts with cells to maintain organ homeostasis [57]. Any alteration of IF composition disturbs the interaction between IF and cells.…”

Selective Enhancement of Domoic Acid Toxicity in Primary Cultures of Cerebellar Granule Cells by Lowering Extracellular Na+ Concentration

“…However, it is possible that drug-induced serum hyponatremia may cause a more severe reduction of extracellular Na þ at the synaptic level. In a recent review, Agnati et al (2017) suggested the existence of local homeostatic differences in the brain interstitial fluid surrounding the neurons, particularly with respect to the concentration of Na þ , finally resulting in lower concentrations in the CSF compared with serum during the circadian rhythm. Thus, it cannot be excluded that drug-induced hyponatremia may eventually become severe enough in synaptic surroundings to facilitate DOM excitotoxicity.…”