These results indicate that the alteration of enzymatic and non-enzymatic crosslinking in bone could be important for explaining the variation of fracture susceptibility in diabetes.
The glymphatic concept along with the discovery of meningeal lymphatic vessels have, in recent years, highlighted that fluid is directionally transported within the central nervous system (CNS). Imaging studies, as well as manipulations of fluid transport, point to a key role of the glymphatic-lymphatic system in clearance of amyloid-β and other proteins. As such, the glymphatic-lymphatic system represents a new target in combating neurodegenerative diseases. Not unexpectedly, introduction of a new plumbing system in the brain has stirred controversies. This opinion article will highlight what we know about the brain's fluid transport systems, where experimental data are lacking, and what is still debated.
The Interconnected Glymphatic-Lymphatic Fluid Transport SystemThe recent discoveries of the brain's glymphatic (glial-lymphatic) (see Glossary) system and the meningeal lymphatic vessels have stirred considerable debate [1][2][3]. An obvious question is why the existence of a brain-wide fluid transport system and the presence of lymphatic vessels in the meningeal layers remained under the radar until now? Before addressing this question, we will here discuss several of the most controversial points. The debates reflect, in part, the fact that critical sets of data have yet to be collected. Other points of controversy are based on debatable assumptions and misunderstandings of the fluid dynamics within the brain. In particular, it is important to stress that the analysis of tracer distribution in histological sections is prone to artifacts. Cardiac arrest or stroke abruptly initiate a pathological influx of cerebrospinal fluid (CSF) [4,5]. As a result, the microscopic localization of CSF tracers in postmortem tissue will inevitably reflect, in part, CSF movements that occurred after death. We will here outline recent developments and add our points to the ongoing debate.
Stroke affects millions each year. Poststroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and treatment options remain limited. In early stages, fluid accumulation occurs owing to a net gain of ions, widely thought to enter from the vascular compartment. Here, we used magnetic resonance imaging, radiolabeled tracers, and multiphoton imaging in rodents to show instead that cerebrospinal fluid surrounding the brain enters the tissue within minutes of an ischemic insult along perivascular flow channels. This process was initiated by ischemic spreading depolarizations along with subsequent vasoconstriction, which in turn enlarged the perivascular spaces and doubled glymphatic inflow speeds. Thus, our understanding of poststroke edema needs to be revised, and these findings could provide a conceptual basis for development of alternative treatment strategies.
According to our data, troglitazone appears to promote fat accumulation in the subcutaneous adipose tissue rather than in the visceral adipose tissue in mildly obese Japanese people with type 2 diabetes. This shift of energy accumulation from the visceral to subcutaneous adipose tissue may greatly contribute to the troglitazone-mediated amelioration of insulin resistance.
A series of mercaptopropyl-functionalized wormhole mesostructures, denoted MP-HMS,
have been prepared through the S0I0 assembly of alkylamine surfactants (S0) and mixtures
of 3-mercaptopropyltrimethoxysilane and tetraethyl orthosilicate as framework precursors
(I0). Unprecedented levels of organo functionalization, corresponding to at least 50% of the
silicon sites, were achieved while retaining well-expressed mesostructures with pore sizes,
pore volumes, and surface areas as high as 2.8 nm, 0.69 cm3/g, and 1225 m2/g, respectively.
Also, up to ∼90% of the framework silicon sites could be fully cross-linked, lending exceptional
hydrothermal stability to the mesostructures. The key to highly functionalized MP-HMS
derivatives lies in the use of long-chain alkylamine surfactants as structure directors (e.g.,
octadecylamine) in combination with a relatively high assembly temperature (e.g., 65 °C)
and a high-polarity water−ethanol solvent. Increasing the assembly temperature increased
both the framework pore size and the degree of framework cross-linking, whereas increasing
the MP content lowered the pore size while improving the framework cross-linking. The
effects of assembly temperature and MP loading were attributable to changes in hydration
at the H-bonded S0I0 interface and concomitant changes in the surfactant packing parameter.
Highly functionalized MP-HMS derivatives are promising materials for use as heavy-metal
ion-trapping agents and as precursors for sulfonic-acid-functionalized mesostructured
catalysts.
Although pain is a common symptom of various diseases and disorders, its contribution to disease pathogenesis is not well understood. Here we show using murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), that pain induces EAE relapse. Mechanistic analysis showed that pain induction activates a sensory-sympathetic signal followed by a chemokine-mediated accumulation of MHC class II+CD11b+ cells that showed antigen-presentation activity at specific ventral vessels in the fifth lumbar cord of EAE-recovered mice. Following this accumulation, various immune cells including pathogenic CD4+ T cells recruited in the spinal cord in a manner dependent on a local chemokine inducer in endothelial cells, resulting in EAE relapse. Our results demonstrate that a pain-mediated neural signal can be transformed into an inflammation reaction at specific vessels to induce disease relapse, thus making this signal a potential therapeutic target.DOI:
http://dx.doi.org/10.7554/eLife.08733.001
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