37 research outputs found

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

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    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

    Can environmental or occupational hazards alter the sex ratio at birth? A systematic review

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    More than 100 studies have examined whether environmental or occupational exposures of parents affect the sex ratio of their offspring at birth. For this review, we searched Medline and Web of Science using the terms ‘sex ratio at birth’ and ‘sex ratio and exposure’ for all dates, and reviewed bibliographies of relevant studies to find additional articles. This review focuses on exposures that have been the subject of at least four studies including polychlorinated biphenyls (PCBs), dioxins, pesticides, lead and other metals, radiation, boron, and g-forces. For paternal exposures, only dioxins and PCBs were consistently associated with sex ratios higher or lower than the expected 1.06. Dioxins were associated with a decreased proportion of male births, whereas PCBs were associated with an increased proportion of male births. There was limited evidence for a decrease in the proportion of male births after paternal exposure to DBCP, lead, methylmercury, non-ionizing radiation, ionizing radiation treatment for childhood cancer, boron, or g-forces. Few studies have found higher or lower sex ratios associated with maternal exposures. Studies in humans and animals have found a reduction in the number of male births associated with lower male fertility, but the mechanism by which environmental hazards might change the sex ratio has not yet been established
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