Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces

Antibiofilm, Antioxidant, Antimutagenic Activities and Phenolic Compounds of Allium orientale BOISS.

ABSTRACT This is the first study to investigate the antibiofilm, antioxidant and antimutagenic activities and phenolic compounds of Allium orientale. Antimicrobial activity of ethanolic extracts of A. orientale was determined by a broth microdilution method. Antibiofilm activity was evaluated by microplate biofilm assay. The antioxidant activity was determined using three complementary assays; namely, DPPH scavenging, β-carotene-linoleic acid, and total phenolic compounds assays. Phenolic compounds were evaluated by reverse-phase high-performance liquid chromatography. The antimutagenic effect of extracts was analyzed by the Ames test. In RP-HPLC analysis, (+)-catechin, apigenin and caffeic acid were identified as major phenolic compounds in the aerial parts of A. orientale. The aerial parts extract possessed the highest total phenolic content (120.979 ± 1.05 mg gallic acid equivalent/g), which were in good correlation with its significant DPPH (IC50 42.18 ± 1.68 mg/mL) and lipid peroxidation (89.98 ± 0.69% at 10 mg/mL concentration) capacities. A. orientale exhibited potent antimicrobial activity against the organisms tested with MICs ranging from 3.125 to 25 mg/mL. Escherichia coli biofilm formation was inhibited maximum by the aerial parts extract to an extent of 68.51%. The strongest antimutagenic activity was observed at 2.5 mg/plate concentration of aerial parts extract against Salmonella typhimurium TA98.These results suggested that the ethanolic extract of the aerial parts of A.orientale could become useful supplement for pharmaceutical products as a new antioxidant, antibiofilm and antimutagenic agent

Analysis of the effects of sex hormone background on the rat choroid plexus transcriptome by cDNA microarrays

The choroid plexus (CP) are highly vascularized branched structures that protrude into the ventricles of the brain, and form a unique interface between the blood and the cerebrospinal fluid (CSF), the blood-CSF barrier, that are the main site of production and secretion of CSF. Sex hormones are widely recognized as neuroprotective agents against several neurodegenerative diseases, and the presence of sex hormones cognate receptors suggest that it may be a target for these hormones. In an effort to provide further insight into the neuroprotective mechanisms triggered by sex hormones we analyzed gene expression differences in the CP of female and male rats subjected to gonadectomy, using microarray technology. In gonadectomized female and male animals, 3045 genes were differentially expressed by 1.5-fold change, compared to sham controls. Analysis of the CP transcriptome showed that the top-five pathways significantly regulated by the sex hormone background are olfactory transduction, taste transduction, metabolism, steroid hormone biosynthesis and circadian rhythm pathways. These results represent the first overview of global expression changes in CP of female and male rats induced by gonadectomy and suggest that sex hormones are implicated in pathways with central roles in CP functions and CSF homeostasis